limitations of phineas gage case study

Phineas Gage: His Accident and Impact on Psychology

Olivia Guy-Evans, MSc

Associate Editor for Simply Psychology

BSc (Hons) Psychology, MSc Psychology of Education

Olivia Guy-Evans is a writer and associate editor for Simply Psychology. She has previously worked in healthcare and educational sectors.

Learn about our Editorial Process

Saul Mcleod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul Mcleod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

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Key Takeaways

In 1848, 25-year-old Phineas Gage survived an accident where an iron rod was propelled through his left cheek and skull. He made an improbable recovery and lived for 12 more years.

Examination of Gage’s exhumed skull in 1867 revealed the probable trajectory of the tamping iron through left frontal lobe structures, offering insight into his improbable survival and selective changes in behavior following this massive traumatic brain injury.

Gage’s case is famous in psychology as it shows the resilience of the human brain and profoundly influenced early understanding of cerebral localization.

What happened to Phineas Gage?

Phineas Gage was an American railroad construction foreman born in 1823 near Lebanon, New Hampshire.

On September 13, 1848, when Gage was 25 years old, he was working in Cavendish, Vermont, leading a crew preparing a railroad bed for the Rutland and Burlington Railroad by blasting away rock using explosives.

Around 4:30 pm, as Gage was using a 43-inch-long, 13-pound iron tamping rod to pack the explosive powder into a hole in the rock, the powder detonated unexpectedly.

The tamping iron launched from the hole and entered the left side of Gage’s face from the bottom up.

The iron rod entered Gage’s left cheek near the lower jaw hinge, passing behind his left eye socket, penetrating the base of his skull, traversing the left frontal lobe upwards at an angle, and exiting through the top frontal portion of his skull before landing about 25-30 yards behind him.

After the incident, Gage was thrown onto his back from the force of the iron rod and had some brief convulsions of the arms and legs.

Within minutes, however, assisted by his crew, Gage could stand, speak, and walk to an oxcart to be transported nearly a mile to the inn where he resided in Cavendish village.

Dr. Edward H. Williams arrived about an hour later to examine Gage. In his 1848 report, Williams noted visible pulsations of Gage’s exposed brain through an inverted funnel-shaped opening at the top of his skull from which brain tissue protruded.

Williams claimed that Gage was recounting his injuries to bystanders, and he did not initially believe the story, thinking that Gage was ‘deceived.’

Apparently, Gage had greeted Williams by angling his head at him and saying, ‘Here’s business enough for you.’

During repeated episodic vomiting, Williams observed additional small amounts of Gage’s brain matter expelled onto the floor through the frontal exit wound, as the cerebral tissue had likely detached from the skull during the passage of the tamping iron.

From Harlow’s written account, Gage was considered to be fully recovered and felt fit enough to reapply for his previous role as a foreman.

After an arduous early recovery, Gage eventually regained physical health, though his personality was markedly altered. He lived another 11 years before dying from severe epilepsy in 1860 at age 36.

How Did Phineas Gage’s Personality Change?

The descriptions of Gage’s personality and behavior before the accident are limited.

Before his accident, 25-year-old Gage was described by his railroad employers as a capable and efficient foreman, displaying a strong work ethic, drive, and dependability in overseeing his crews.

However, after surviving passage of the tamping iron through his frontal lobe in 1848, significant changes in Gage’s personality emerged during his physical recovery.

The contractors, who had regarded Gage as ‘efficient and capable’ before the accident, could no longer offer him work due to considerable changes in Gage’s personality.

In medical reports by Dr. John Martyn Harlow in 1848 and 1868, Gage is depicted as struggling with volatility, profanity, little deference for others, impatience, obstinance, unpredictability, and devising plans hastily abandoned.

Harlow wrote that Gage’s equilibrium between intellectual faculties and animal propensities was destroyed, reverting to childlike mental capacity regarding self-restraint and social appropriateness.

Though the specific neuroanatomical links were unclear at the time, Friends and colleagues felt Gage was “no longer Gage” after the traumatic brain injury, unable to process emotions or control impulsive behavior like his pre-accident self.

The shocking changes aligned with emerging localization theories that the frontal lobes regulate personality.

Marlow (1868) described Gage as follows:

“The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operations, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man.”

“Previous to his injury, though untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart business man, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage.”

Through Harlow’s reports, it can be suggested that Gage’s personality changed due to the accident he endured.

The accounts imply that the injury led to a loss of social inhibition, meaning that Gage would behave in ways that were considered inappropriate.

Accuracy of Sources

In his 1848 and 1868 reports, Dr. Harlow provides a limited description of Gage’s pre-accident, stating he was “temperate inhabit, of great energy of character, possessed of considerable stamina of both brain and body” and was “a great favorite” with his men (Harlow, 1848, 1868).

However, later accounts add exaggerated positive traits not found in Harlow’s description. For example, Suinn (1970) describes Gage as enjoying “the respect as well as the favor of his men,” while Myers (1998) calls him “soft-spoken,” and Lahey (1992) says he was “polite and reasonable.”

Other sources paint him as friendly, affable, dependable, conscientious, and happy (Macmillan, 2000).

Similarly, post-accident descriptions often emphasize Gage’s negative qualities while ignoring any positive traits he retained.

Harlow documents personality changes but notes Gage remained employable for a period as a long-distance stagecoach driver in Chile (Harlow, 1868).

However, many accounts focus solely on traits like aggression, unreliability, or aimlessness (Macmillan, 2000). Damasio goes so far as to describe him as behaving violently with no self-control (Blakeslee, 1994).

In this way, later accounts tend to polish Gage’s pre-accident image as an upstanding citizen while presenting an almost cartoonishly perturbed version post-injury – neither in keeping with Harlow’s more nuanced clinical descriptions.

This likely reflects enthusiasm for fitting Gage’s case to localization theories. Macmillan (2000) argues that we must cautiously analyze such embellished personality descriptions when assessing Phineas Gage’s legacy.

Severity of Gage’s Brain Damage

When Gage died in 1861, no autopsies were performed until his skull was later recovered by Harlow years later. The brain damage that caused the significant personality changes was presumed to have involved the left frontal region of the brain.

It was not until 1994 that complex computer-based methods to examine brain damage could be used to investigate whether other areas of the brain were affected.

Phineas Gage brain image from Damasio et al. (1994)

Damasio et al. (1994) used measurements from Gage’s skull and neuroimaging techniques to determine the exact placement of the entry and exit point of the iron rod on a replica model (see Fig. 1).

They found that the damage caused by the rod involved both the left and right prefrontal cortices.

The left and right cortices are responsible for emotional processing and rational decision-making; therefore, it can be assumed that Gage had deficits in these areas.

Phineas Gage brain image from Ratiu et al., (2004)

A later study by Ratiu et al. (2004) also investigated Gage’s injury and the location of where the iron rod entered and exited the head. They used Gage’s actual skull rather than a model of it, as Damasio et al. (1994) had used.

Ratiu et al. (2004) generated three-dimensional reconstructions of the skull using computed tomography scans (CAT) and found that the extent of the brain injury was limited to the left frontal lobe only and did not extend to the right lobe (see Fig. 2).

Phineas Gage MRI brain image from Van Horn et al., (2012)

More recently, Van Horn et al. (2012) used a CAT scan of Gage’s skull as well as magnetic resonance imaging (MRI) data obtained from male participants of a similar age to Gage at the time (aged 25-36).

Their results supported Ratiu et al. (2004) in that they always concluded that the rod only damaged the left lobe and not the right.

Van Horn, however, went a step further in their research and investigated the potential levels of white and grey matter damaged due to Gage’s injury. White matter is deep in the brain and provides vital connections around the brain, essential to normal motor and sensory function.

Grey matter in the brain is essential to many areas of higher learning, including attention, memory, and thought.

The research by Van Horn proposed that Gage lost about 11% of his white matter and about 4% of his grey matter. White matter has the ability to regenerate, so this could explain why Gage recovered as well as he did.

Van Horn et al. (2012) compared Gage’s white matter damage to the damage that is caused by neurogenerative diseases such as Alzheimer’s.

This is supported by other studies that have found that changes in white matter is significantly associated with Alzheimer’s disease (Nasrabady, Rizvi, Goldman & Brickman, 2018; Kao, Chou, Chen & Yang, 2019).

It could be suggested that Gage’s apparent change in personality could have been the result of an early onset of Alzheimer’s.

However, as Dr. Harlow, who examined Gage, only reported on Gage’s behaviors shortly after his accident, rather than months or years later when Alzheimer’s symptoms may have emerged, we cannot be certain whether Gage actually had this condition.

All studies investigating the brain damage suffered by Gage is essentially all speculation as we cannot know for certain the extent of the accident’s effects.

We know that some brain tissue got destroyed, but any infections Gage may have suffered after the accident may have further destroyed more brain tissue.

We also cannot determine the exact location where the iron rod entered Gage’s skull to the millimeter. As brain structure varies from person to person, researchers cannot ever know for certain what areas of Gage’s brain were destroyed.

What Happened to Phineas Gage After the Brain Damage?

Dr. John Martyn Harlow took over Gage’s case soon after. Harlow (1848) reported that Gage was fully conscious and recognized Harlow immediately but was tired from the bleeding.

In the next couple of days, Harlow observed that Gage spoke with some difficulty but could name his friends, and the bleeding ceased. Gage then spent September 23rd to October 3rd in a semi-comatose state but was able to take steps out of bed by October 7th.

By October 11th, Harlow claimed Gage’s intellectual functioning began to improve. He recognized how much time had passed since the accident and could describe the accident clearly.

Four years after his injury, Gage moved to Chile and worked taking care of horses and being a stagecoach driver.

Harlow noted emerging personality changes in this period, with Gage becoming more erratic in behavior and responsibility.

In 1860, Gage moved to San Francisco to live near family but began suffering epileptic seizures – likely related to scar tissue and injury sequelae.

The convulsions worsened over months, and on May 21, 1861, almost 13 years after his shocking accident, Gage died at age 38 from complications of severe epilepsy.

How did Phineas Gage die?

On May 21st, 1861, twelve years after his accident, Gage died after having a series of repeated epileptic convulsions.

In 1867, Harlow arranged an exhumation of Gage’s body, claiming his skull and tamping iron for medical study.

These historic artifacts remain on display at the Harvard School of Medicine.

Though Gage initially survived, it was the secondary long-term effects of this massive brain injury that ultimately led to his premature death over a decade later.

Why Is Phineas Gage Important to Psychology?

Gage’s case is important in the field of neuroscience . The reported changes in his behavior post-accident are strong evidence for the localization of brain function , meaning that specific brain areas are associated with certain functions.

Neuroscientists have a better understanding of the function of the frontal cortex today. They understand that the frontal cortex is associated with language, decision-making, intelligence, and reasoning functions. Gage’s case became one of the first pieces of evidence suggesting that the frontal lobe was directly involved in personality.

It was believed that brain lesions caused permanent deficits in a person. However, Gage was proven to have recovered remarkably and lived a mostly normal life despite his injury. It was even suggested by a psychologist called Malcolm Macmillan that Gage may have relearned lost skills.

People with damage to their frontal lobes tend to have trouble completing tasks, get easily distracted, and have trouble planning.

Despite this damage to his frontal lobe, Gage was reported to have worked as a coach driver which would have involved Gage being focused and having a routine, as well as knowing his routes and multitasking.

Macmillan (2002), therefore, suggests that Gage’s damage to the frontal lobe could have somewhat repaired itself and recovered lost functions. The ability of the brain to change in this way is called brain plasticity .

Over time, Gage’s story has been retold, and this has sometimes led to a lot of exaggeration as to the personality changes of Gage.

Some popular reports described him as a hard-working, kind man prior to the accident and then described him as an aggressive, dishonest, and drunk man who could not hold down a job and died pennilessly.

Gage’s story seemed to take on a life of its own, and some even went as far as to say that Gage became a psychopath after his accident, without any facts behind this.

From the actual reports from the people in contact with Gage at the time, it appears that his personality change was nowhere near as extreme and that Gage was far more functional than some reports would have us believe (Macmillan, 2002).

Blakeslee, S. (1994, July 6). A miraculous recovery that went wrong . New York Times.

Damasio, H., Grabowski, T., Frank, R., Galaburda, A. M., & Damasio, A. R. (1994). The return of Phineas Gage: clues about the brain from the skull of a famous patient . Science, 264 (5162), 1102-1105.Harlow J. M. (1848). Passage of an iron rod through the head. Boston Medical and Surgical Journal, 39 , 389–393.

Harlow, J. M. (1868). Recovery from the Passage of an Iron Bar through the Head . Publications of the Massachusetts Medical Society. 2 (3), 327-347.

Kao, Y. H., Chou, M. C., Chen, C. H., & Yang, Y. H. (2019). White matter changes in patients with Alzheimer’s disease and associated factors . Journal of Clinical Medicine, 8 (2), 167.

Lahey, B. B. (1992). Psychology: An introduction . Wm. C. Brown Publishers.

Macmillan, M. (2000). Restoring Phineas Gage: A 150th retrospective. Journal of the History of the Neurosciences, 9 (1), 46-66.

Macmillan, M. (2002). An odd kind of fame: Stories of Phineas Gage. MIT Press.

Myers, D. G. (1998). Psychology (5th ed.). Worth Publishers.

Nasrabady, S. E., Rizvi, B., Goldman, J. E., & Brickman, A. M. (2018). White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta neuropathologica communications, 6 (1), 1-10.

Ratiu, P., Talos, I. F., Haker, S., Lieberman, D., & Everett, P. (2004). The tale of Phineas Gage, digitally remastered . Journal of neurotrauma, 21 (5), 637-643.

Suinn, R. M. (1970). Fundamentals of behavior pathology. Wiley.

Van Horn, J. D., Irimia, A., Torgerson, C. M., Chambers, M. C., Kikinis, R., & Toga, A. W. (2012). Mapping connectivity damage in the case of Phineas Gage . PloS one, 7(5) , e37454.

If a person suffers from a traumatic brain injury in the prefrontal cortex, similar to that of Phineas Gage, what changes might occur?

A traumatic brain injury to the prefrontal cortex could result in significant changes in personality, emotional regulation, and executive function. This region is vital for impulse control, decision-making, and moderating social behavior.

A person may exhibit increased impulsivity, poor judgment, and reduced ability to plan or organize. Emotional volatility and difficulty in interpersonal relationships may also occur.

Just like the case of Phineas Gage, who became more impulsive and less dependable, the injury could dramatically alter one’s character and abilities.

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Phineas Gage

In this post

You may have already heard of Phineas Gage, such is his infamous history with psychology. He was working on a railway line in the USA when there was an explosion, which resulted in an iron rod being fired through his head. He survived the accident even though there were serious injuries to his face and brain but it was soon discovered that in terms of his personality, he was completely different after the accident than he was before it.

Before the accident he was described as a very calm man who was very popular, but afterwards he was considered to be rude and irresponsible.

Gage died 12 years after the accident and after hearing of his death, his doctor, John Harlow, who had worked with him at the time of his accident, asked for his body to be exhumed so that he could look at his skull and try to identify how this caused the change in his personality.

Many years later, Damasio and her colleagues were able to make use of much better technology to further investigate the damage that had been caused to Phineas Gage’s brain and the effects that this had on his personality.

Damasio et al. aimed to build a replica model of Gage’s skull (using the actual skull as a guide) so that they could show exactly where the iron rod entered and exited Gage’s head.

A 3D representation of the skull and the injuries it received meant that it was much clearer which parts of his brain would have been affected by the accident and Damasio et al. wanted to see if any other areas of the brain had also been damaged.

Pictures and measurements of Gage’s skull were taken
A 3D replica model was built based on the information from the skull
Information was also taken from the iron rod (which had been buried with Gage!)
Information from the rod and the skull together meant that the trajectory of the iron rod could be accurately mapped
Altogether 20 different points of entry and 16 points of exit were identified and the five most likely paths were chosen
Each of these five paths were explored to map out which areas of Gage’s brain would have been damaged by each path.

It was thought that damage to both the left and right hemispheres of the brain were likely and that no other area than the frontal lobe would have been affected.

The iron rod would have gone through Gage’s left eye socket and then upwards in its trajectory. This means that rather than affecting the right frontal lobe, only the white matter (tissue containing nerve fibres) in the brain’s left hemisphere would have been affected. However, this meant that neural messages in this area of the brain would not have been transmitted because white matter is where neurons pass messages along axon fibres.

The findings from the 3D model and its implications for the parts of the brain that were thought to be damaged were compared to reports of the changes in Gage’s personality. It was concluded that a specific area of the frontal lobe (the ventromedial area) is responsible for making controlled decisions, regulating impulses and urges and dealing with emotions in a proper way.

These findings were compared to 12 other individuals who had experienced similar brain injuries and the same problems with control and impulse were found, showing that it is likely possible to predict the behaviour of people who have sustained this kind of brain injury.

Strengths of the study

Modern-day technology is very reliable and therefore the 3D model that was created would have been very accurate and information could be ‘seen’ rather than just guessed at from written reports
Predictions can now be made about people’s behaviour when they have experienced injuries in specific areas of the brain; this can help people to adjust to new lifestyles and may help in treating them as well.

Weaknesses of the study

Information about the change in Gage’s personality were gleaned from details written more than a century ago, meaning its accuracy is questionable
As this was a case study, it is difficult to generalise the findings to a wider population so predictions about possible changes in behaviour may not be applicable to everyone.

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The Disappearing Spoon

The Disappearing Spoon podcast

Everything you know about phineas gage is wrong.

What can a railroad construction foreman’s devastating skull injury teach us about the brain’s ability to heal?

A portrait of Phineas Gage holding a piece of iron.

Despite what you’ve heard, neuroscience’s most famous patient did not turn into a lying, drunken psychopath. He’s actually an amazing example of resiliency and overcoming trauma.

About The Disappearing Spoon

The Science History Institute has teamed up with New York Times best-selling author Sam Kean to bring a second history of science podcast to our listeners. The Disappearing Spoon tells little-known stories from our scientific past—from the shocking way the smallpox vaccine was transported around the world to why we don’t have a birth control pill for men . These topsy-turvy science tales, some of which have never made it into history books, are surprisingly powerful and insightful.

Host: Sam Kean Senior Producer: Mariel Carr Producer: Rigoberto Hernandez Audio Engineer: Jonathan Pfeffer

It was a lovely September day in 1848. A construction foreman named Phineas Gage was helping lay track for a railroad company in Vermont. Some boulders were blocking the railroad’s path, so the company hired a gang of rowdy Irishmen to blast their way through.

As foreman, Gage supervised the Irishmen. He also helped drill holes into the boulders and fill them with gunpowder. Gage then packed the gunpowder down into the hole with an iron rod. The rod looked like a short javelin. It was 1¼ inches thick, stretched 3 ½ feet long, and weighed 13 pounds.

Around 4:30pm, the Irishmen were loading some busted rock onto a cart. It was near quitting time, so perhaps they were a-whooping and a-hollering. Gage had just finished pouring gunpowder into a hole, and turned his head.

Accounts differ about what happened next. Some say that Gage was packing the gunpowder down with the iron rod, and scraped it against the side of the hole, creating a spark. Regardless, a spark shot out somewhere inside the hole and ignited the gunpowder. At which point the iron rod reversed thrusters.

The iron rod blasted upward, and entered Gage’s skull below his left cheekbone. It destroyed a molar, pierced his left eye, and plowed into his brain’s left frontal lobe. The rod then exited on top, and landed twenty-five yards distant. One report claimed it whistled as it flew, and was streaked with blood.

The rod’s momentum threw Gage backward. He landed hard. Amazingly, though, he never lost consciousness. He twitched a few times on the ground, but was talking within minutes. He even walked under his own power to a nearby cart, and sat upright on the trip back to town.

At his hotel, Gage waited in a chair on the porch and chatted with passersby—who were, uh, startled to see a volcano of bone jutting out of his scalp.

Thus began perhaps the most famous case in medical history. Every neuroscience textbook in existence has a section on Phineas Gage. Incredibly, though, nearly every textbook gets the story wrong.

You might have heard that, after his injury, Gage became a criminal, a drunk, a psychopath. None of that’s true.

Instead, there’s good evidence that, far from turning toward the dark side, Gage recovered after his accident—and perhaps resumed something like a normal life. It’s a possibility that, if true, could transform our understanding of the brain’s ability to heal.

When the first doctor arrived, Phineas Gage greeted him by angling his head and saying, “Here’s business enough for you.” Finally, around 6pm, the first doctor turned the case over to Dr. John Harlow. It’s not clear why. Harlow was a country doctor. He mostly treated people who’d fallen off horses. Not neurological cases.

Harlow didn’t believe Gage’s story at first. Surely, the rod hadn’t passed through his skull? But it had: Gage had a flap in his cheek and everything. Harlow then watched Gage lumber upstairs to his hotel room and lie on the bed. Which ruined the linens, since his upper body was one big bloody mess.

In the room, Harlow shaved Gage’s scalp and peeled off the dried blood and brains. Harlow then extracted skull fragments from the wound. Throughout this all, Gage vomited every twenty minutes. But otherwise, he remained calm and lucid. He betrayed no discomfort or pain.

Over the next few days, an infection set in and Gage’s brain swelled dangerously. Things were touch and go for a week, and Gage lapsed into a coma. A local cabinetmaker measured him for a coffin.

But Harlow’s diligent care allowed Gage to pull through. Gage soon returned to his family farm on Potato Road to recover. Gage did lose his left eye, but his memory, language, and motor skills remained intact. All in all, he seemed almost normal.

Almost. Harlow had kept Gage alive, but Gage’s family swore that he’d changed. The man who returned home was not the same man they knew and loved. His memory, language, and motor skills remained intact. But his personality changed.

Before the accident, Gage was known for making plans and sticking to them. Afterward, he changed his mind willy-nilly and rarely stuck things through. Before, Gage was also indifferent to animals. Afterward, Gage adored critters of all kinds. And while the original Gage was courteous and polite in company, the new Gage was coarse and foul-mouthed.

Most strikingly, Gage lost all money sense and developed irrationally strong attachments to certain objects. Harlow once tested Gage by offering him money for some random pebbles that Gage had picked out of a stream. Gage refused to part with them even for $1,000. Gage also carried with him at all times the iron rod that had brained him.

Harlow summed up Gage’s new personality by saying that, quote, the “balance … between his intellectual faculties and his animal propensities seems to have been destroyed.” More pithily, friends said that Gage “was no longer Gage.”

Despite his stellar work record before, the railroad refused to reinstate Gage as foreman. He took to working odd jobs on farms instead. He also indulged his newfound love of horses and became a carriage driver in New Hampshire. At one point, Gage even exhibited himself at P.T. Barnum’s freakshow museum in New York, staring back at the audience with his one good eye. For an extra dime skeptics could part his hair and watch his brain pulsate through a flap of skin over the exit wound in his skull.

After his stint at the museum, Gage’s life gets murky for a few years. Facts are hard to come by. But that hasn’t stopped scientists from filling that vacuum of facts with rumors and unfounded speculation.

One rumor claimed that Gage developed a drinking problem and started getting into brawls at taverns. Another claimed that he became a scam artist. He supposedly went to a medical school and sold them the exclusive rights to keep and study his skull after he died. Then he went to another medical school—and sold the same rights. And then another school, and another, skipping town and pocketing the cash each time. One ridiculous source even claimed that Gage lived for a dozen years with the iron rod still impaled in his noggin.

Other rumors in modern textbooks contradict each other. Some sources describe Gage as sexually indifferent, while others call him promiscuous. Some sources say he was hot-tempered, while others call him emotionally void, as if lobotomized. One neuroscientist even claimed that Gage “had lost his soul.”

To be clear, there’s zero historical evidence for any of those rumors of Gage’s mental or physical decline. In fact, in the only known picture of Gage, he looks nothing like a wastrel or someone whose life is spiraling out of control. He’s proud, well-dressed, even handsome.

To be clear, Harlow’s reports make it clear that Gage’s personality changed somehow. It’s about the only hard fact we have, neurologically speaking. But his other comments about Gage’s mental state are ambiguous.

Take the comment about Gage’s life being taken over by “animal propensities.” That sounds dramatic, but what does that mean—“animal propensities”? Did he eat too much? Demand sex? Howl at the moon? We have no idea.

Or consider this. In addition to loving animals after his accident, Gage also felt drawn to children suddenly. And on his visits home, Gage would reportedly spin wild tales for his nieces and nephews. Made-up stories about his supposed adventures on the road.

Some neuroscientists have interpreted Gage’s storytelling as evidence of confabulation. It’s a neurological symptom that involves chronic lying. It usually arises after frontal lobe damage. Then again, who hasn’t made up a tall tale to make little kids laugh? They love that stuff. It’s a pretty weak case for brain damage.

Similarly, we know that Gage had trouble sticking to plans after his accident. That’s another sign of frontal-lobe damage, because the frontal lobe controls mental skills like reasoning, planning, and self-control. In addition, Gage seemed to lose the impulse control that prevents most people from swearing in public. But it’s a far cry from someone saying saucy words like “hell” and “damn” to claiming that Gage was a drunken, brawling criminal.

In all, Gage’s life story, as appears in textbooks, has become as much legend as fact—a mélange of scientific prejudice, artistic license, and outright fabrication. Most people who learn about Gage in classes or textbooks have no idea how weak the case is for Gage becoming a villain.

Moreover, some modern historians have argued, forcefully, that Gage seems to have recovered some of his faculties in the decade after his accident. He never became the Phineas Gage of old. But some of his negative traits either diminished or disappeared, possibly because his brain proved plastic enough to heal and recover some lost functions.

In 1852, Phineas Gage’s life took a dramatic turn. He left the New England of his youth and followed a gold rush down to Chile in South America. He was seasick the whole voyage. Once ashore, he found work driving a horse carriage. His job involved shuttling passengers along the rugged, mountainous trails between Valparaiso and Santiago.

Gage held this job for seven years. Which is staggering, considering both his brain damage, and the complexity of the work. Gage likely drove a team of six horses. And horse reins at the time were complicated because you had to control each horse separately.

For instance, consider rounding a bend. To do so without tipping the coach over, you had to slow down the inner three horses a touch more than the outer three horses, simply by tugging on their reins with varying amounts of pressure. That would have taken a lot of dexterity. I mean, imagine driving a car while steering all four wheels independently. This could not have been easy for someone with brain damage.

Especially because the trails in Chile were quite crowded. This would have forced Gage to make quick stops and dodge other carriages. And because he probably drove at night sometimes, he would have had to memorize the trail’s twists and turns and fatal drop-offs. Plus keep an eye out for bandits.

Gage also likely cared for his horses by grooming and feeding them—a significant responsibility. And, contradicting the claim that he lacked all money sense, Gage probably collected passenger fares. Not to mention that he presumably picked up some conversational Spanish while in Chile—no mean feat for any adult.

You wonder how many of Gage’s passengers would have climbed aboard had they known about their one-eyed driver’s little accident a few years earlier. But all in all, Gage seems to have handled himself fine.

It probably helped Gage that he followed a similar routine each day. He likely arose before dawn to prepare his horses and carriage. Then he spent the next thirteen hours driving the same road back and forth from Valparaiso to Santiago.

Now, the fact that Gage seemingly carved out a life for himself in Chile doesn’t mean that his brain recovered fully. But scientists now know that the brain’s neural circuits can recover somewhat after damage, partly by rewiring themselves. And perhaps Gage retained enough of his frontal lobes to retain some basic planning skills. At the very least, Gage didn’t deteriorate into the drunken sociopath that many modern textbooks claim.

In truth, those claims about Gage are probably influenced by modern cases of brain damage. Cases where people did turn into sociopaths. You can hear more in a bonus episode at patreon.com/disappearingspoon. People who gambled money wildly, abandoning their family, and suddenly become pedophiles. That’s patreon.com/disappearingspoon.

Sadly, despite building a life for himself in Chile, Gage couldn’t outrun his brain damage entirely. And when it did catch up to him, the end was swift.

Poor health forced Gage to leave Chile in 1859. He caught a steamer up to San Francisco, where his family had moved. After a few months of rest in California, Gage found work on a farm and seemed to be doing better.

Unfortunately, a punishing day of plowing in early 1860 wiped him out. He had a seizure the next night over dinner. More seizures followed.

Gamely, Gage tried to keep working during this spell of trouble. But after years of steady work in South America, the seizures made him restless and capricious again. He began drifting from farm to farm, quitting each job for unknown reasons.

Finally, on May 20th, 1860, while resting at his mother’s home, he had several violent seizures in a row. He died the next day at age thirty-six, having survived his accident by almost a dozen years.

Gage’s skull was later exhumed by doctors. It remains on display at Harvard University today, along with the iron rod that remodeled his brain. Oddly, his skull has become something of a pilgrimage spot for people with an interest in macabre history.

I’ve spent a lot of time in this podcast bemoaning the lack of hard facts about Gage’s life. But in truth, that dearth of details probably secured Gage’s fame. That lack left infinite room for interpretation, and allowed each generation of scientists to reinterpret his case anew. Everyone from legendary neurosurgeons to phrenologists reading head bumps have invoked Gage to support their pet theories. Overall, Gage has become a Rorschach blot for neuroscientists. What we think of him changes from era to era, as the obsessions and preoccupations of each era change.

Including our era. Nowadays scientists cite Gage in support of theories about multiple intelligences; emotional intelligence; the social nature of the self; brain connectivity; every modern neuro-obsession.

And what Phineas Gage means now will probably change in the future, too. In fact, Gage’s story will probably always be with us. In part because it’s a hell of a story! Once upon a time, a man with a funny name really did survive having an iron rod explode through his skull. It’s tragic, gruesome, bewildering—and even comes with a science lesson.

But the deeper reason that Gage will always be with us is this. Despite all that remains murky and obscure, his life can teach us something important—that the brain and mind are one. After all, about the only hard fact we know is that his personality did change. And that’s no small thing.

As one neuroscientist has written, “beneath the tall tales and fish stories, a basic truth embedded in Gage’s story has played a tremendous role in shaping modern neuroscience: that the brain is the physical manifestation of the personality and sense of self.” That’s a profound idea, and it was Phineas Gage who first pointed us toward that truth.

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Phineas Gage: His Accident and Impact on Psychology

Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

Emily is a board-certified science editor who has worked with top digital publishing brands like Voices for Biodiversity, Study.com, GoodTherapy, Vox, and Verywell.

Author unknown / Wikimedia Commons

Phineas Gage's Accident
Change in Personality
Severity of Brain Damage
Impact on Psychology

What Happened to Phineas Gage After the Brain Damage?

Phineas Gage is often referred to as the "man who began neuroscience." He experienced a traumatic brain injury when an iron rod was driven through his skull, destroying much of his frontal lobe .

Gage miraculously survived the accident. However, his personality and behavior were so changed as a result of the frontal lobe damage that many of his friends described him as an almost different person entirely. The impact that the accident had has helped us better understand what the frontal lobe does, especially in relation to personality .

At a Glance

In 1848, Phineas Gage had a workplace accident in which an iron tamping rod entered and exited his skull. He survived but it is said that his personality changed as a result, leading to a greater understanding of the brain regions involved in personality, namely the frontal lobe.

Phineas Gage's Accident

On September 13, 1848, 25-year-old Gage was working as the foreman of a crew preparing a railroad bed near Cavendish, Vermont. He was using an iron tamping rod to pack explosive powder into a hole.

Unfortunately, the powder detonated, sending the 43-inch-long, 1.25-inch-diameter rod hurling upward. The rod penetrated Gage's left cheek, tore through his brain , and exited his skull before landing 80 feet away.

Gage not only survived the initial injury but was able to speak and walk to a nearby cart so he could be taken into town to be seen by a doctor. He was still conscious later that evening and able to recount the names of his co-workers. Gage even suggested that he didn't wish to see his friends since he would be back to work in "a day or two" anyway.

The Recovery Process

After developing an infection, Gage spent September 23 to October 3 in a semi-comatose state. On October 7, he took his first steps out of bed, and, by October 11, his intellectual functioning began to improve.

Descriptions of Gage's injury and mental changes were made by Dr. John Martyn Harlow. Much of what researchers know about the case is based on Harlow's observations.

Harlow noted that Gage knew how much time had passed since the accident and remembered clearly how the accident occurred, but had difficulty estimating the size and amounts of money. Within a month, Gage was well enough to leave the house.

In the months that followed, Gage returned to his parent's home in New Hampshire to recuperate. When Harlow saw Gage again the following year, the doctor noted that while Gage had lost vision in his eye and was left with obvious scars from the accident, he was in good physical health and appeared recovered.

Theories About Gage's Survival and Recovery

The type of injury sustained by Phineas Gage could have easily been fatal. While it cannot be said with certainty why Gage was able to survive the accident, let alone recover from the injury and still function, several theories exist. They include:

The rod's path . Some researchers suggest that the rod's path likely played a role in Gage's survival in that if it had penetrated other areas of the head—such as the pterygoid plexuses or cavernous sinus—Gage may have bled to death.
The brain's selective recruitment . In a 2022 study of another individual who also had an iron rod go through his skull—whom the researchers referred to as a "modern-day Phineas Gage"—it was found that the brain is able to selectively recruit non-injured areas to help perform functions previously assigned to the injured portion.
Work structure . Others theorize that Gage's work provided him structure, positively contributing to his recovery and aiding in his rehabilitation.

How Did Phineas Gage's Personality Change?

Popular reports of Gage often depict him as a hardworking, pleasant man before the accident. Post-accident, these reports describe him as a changed man, suggesting that the injury had transformed him into a surly, aggressive heavy drinker who was unable to hold down a job.

Harlow presented the first account of the changes in Gage's behavior following the accident. Where Gage had been described as energetic, motivated, and shrewd prior to the accident, many of his acquaintances explained that after the injury, he was "no longer Gage."

Severity of Gage's Brain Damage

Since there is little direct evidence of the exact extent of Gage's injuries aside from Harlow's report, it is difficult to know exactly how severely his brain was damaged. Harlow's accounts suggest that the injury did lead to a loss of social inhibition, leading Gage to behave in ways that were seen as inappropriate.

In a 1994 study, researchers utilized neuroimaging techniques to reconstruct Phineas Gage's skull and determine the exact placement of the injury. Their findings indicate that he suffered injuries to both the left and right prefrontal cortices, which would result in problems with emotional processing and rational decision-making .

Another study conducted in 2004 used three-dimensional, computer-aided reconstruction to analyze the extent of Gage's injury. It found that the effects were limited to the left frontal lobe.

In 2012, new research estimated that the iron rod destroyed approximately 11% of the white matter in Gage's frontal lobe and 4% of his cerebral cortex.

Some evidence suggests that many of the supposed effects of the accident may have been exaggerated and that Gage was actually far more functional than previously reported.

Why Is Phineas Gage Important to Psychology?

Gage's case had a tremendous influence on early neurology. The specific changes observed in his behavior pointed to emerging theories about the localization of brain function, or the idea that certain functions are associated with specific areas of the brain.

In those years, neurology was in its infancy. Gage's extraordinary story served as one of the first sources of evidence that the frontal lobe was involved in personality.

Today, scientists better understand the role that the frontal cortex has to play in important higher-order functions such as reasoning , language, and social cognition .

After the accident, Gage was unable to continue his previous job. According to Harlow, Gage spent some time traveling through New England and Europe with his tamping iron to earn money, supposedly even appearing in the Barnum American Museum in New York.

He also worked briefly at a livery stable in New Hampshire and then spent seven years as a stagecoach driver in Chile. He eventually moved to San Francisco to live with his mother as his health deteriorated.

After a series of epileptic seizures, Gage died on May 21, 1860, almost 12 years after his accident. Seven years after his death, Gage's body was exhumed. His brother gave his skull and the tamping rod to Dr. Harlow, who subsequently donated them to the Harvard University School of Medicine. They are still exhibited in its museum today.

Bottom Line

Gage's accident and subsequent experiences serve as a historical example of how case studies can be used to look at unique situations that could not be replicated in a lab. What researchers learned from Phineas Gage's skull and brain injury played an important role in the early days of neurology and helped scientists gain a better understanding of the human brain and the impact that damage could have on both functioning and behavior.

Sevmez F, Adanir S, Ince R. Legendary name of neuroscience: Phineas Gage (1823-1860) . Child's Nervous System . 2020. doi:10.1007/s00381-020-04595-6

Twomey S. Phineas Gage: Neuroscience's most famous patient . Smithsonian Magazine.

Harlow JM. Recovery after severe injury to the head . Bull Massachus Med Soc . 1848. Reprinted in Hist Psychiat. 1993;4(14):274-281. doi:10.1177/0957154X9300401407

Harlow JM. Passage of an iron rod through the head . 1848. J Neuropsychiatry Clin Neurosci . 1999;11(2):281-3. doi:10.1176/jnp.11.2.281

Itkin A, Sehgal T. Review of Phineas Gage's oral and maxillofacial injuries . J Oral Biol . 2017;4(1):3.

de Freitas P, Monteiro R, Bertani R, et al. E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury . The Lancet Regional Health - Americas . 2022;14:100340. doi:10.1016/j.lana.2022.100340

Macmillan M, Lena ML. Rehabilitating Phineas Gage . Neuropsycholog Rehab . 2010;20(5):641-658. doi:10.1080/09602011003760527

O'Driscoll K, Leach JP. "No longer Gage": An iron bar through the head. Early observations of personality change after injury to the prefrontal cortex . BMJ . 1998;317(7174):1673-4. doi:10.1136/bmj.317.7174.1673a

Damasio H, Grabowski T, Frank R, Galaburda AM, Damasio AR. The return of Phineas Gage: Clues about the brain from the skull of a famous patient . Science . 1994;264(5162):1102-5. doi:10.1126/science.8178168

Ratiu P, Talos IF. Images in clinical medicine. The tale of Phineas Gage, digitally remastered . N Engl J Med . 2004;351(23):e21. doi:10.1056/NEJMicm031024

Van Horn JD, Irimia A, Torgerson CM, Chambers MC, Kikinis R, Toga AW. Mapping connectivity damage in the case of Phineas Gage . PLoS One . 2012;7(5):e37454. doi: 10.1371/journal.pone.0037454

Macmillan M. An Odd Kind of Fame: Stories of Phineas Gage . MIT Press.

Shelley B. Footprints of Phineas Gage: Historical beginnings on the origins of brain and behavior and the birth of cerebral localizationism . Archives Med Health Sci . 2016;4(2):280-6. doi:10.4103/2321-4848.196182

By Kendra Cherry, MSEd Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

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The Oxford Handbook of the History of Clinical Neuropsychology

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41 Phineas Gage: A Neuropsychological Perspective of a Historical Case Study

Alan G. Lewandowski, Clinical Neuropsychologist, Neuropsychology Associates

Joshua D. Weirick, Post-Doctoral Research Fellow, Department of Speech, Language and Hearing Sciences, Purdue University

Caroline A. Lewandowski, Private Practice

Jack Spector, Clinical Neuropsychologist, Independent Practice

Published: 07 May 2020
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The case of Phineas Gage is one of the most frequently cited cases from 19th century medical literature and represents the first of a series of famous cases involving the brain and behavior. While many reiterations of Gage’s case have been published, it remains important to modern neuroscience due to its unique historical significance, ongoing clinical relevance, and the insights it offers neuropsychology into the functional effects of brain injury on thinking, emotions, and behavior. This chapter revisits the critical aspects of this landmark case from a contemporary clinical perspective and discusses the implications of injury to the prefrontal cortex and pathways.

Introduction

On Wednesday, September 13, 1848, a construction crew working for the Rutland and Burlington Railroad near Duttonsville, Vermont, was excavating rock to prepare the ground for track that was soon to be laid. In charge of the crew was a 25-year-old foreman named Phineas Gage, who was using an iron bar to pack black powder into a hole that had been drilled into the rock. For an unknown reason, a spark ignited the black powder and the ensuing explosion propelled the metal rod through the left side of Gage’s face, entering at a slight angle below his zygomatic arch. It passed behind his left eye, through the left frontal lobe, and exited the skull anterior to the juncture of the sagittal and coronal sutures, landing about one hundred feet behind him. Incredibly, Gage endured the injuries and lived another eleven and a half years. Due to his survival of an accident of this magnitude, he entered into the annals of scientific and historical literature as a frequently cited example of a frontal cortical injury.

One week after the accident, on September 21, 1848, the Free Soil Union newspaper in Ludlow, Vermont, published the following account:

Horrible Accident—As Phineas P. Gage, a foreman on the railroad in Cavendish, was yesterday engaged in tamkin [sic] for a blast, the powder exploded, carrying an iron instrument through his head an inch and a fourth in circumference, and three feet and eight inches in length, which he was using at the time. The iron entered on the side of his face, shattering the upper jaw, and passing back of the left eye, and out at the top of his head. The most singular circumstance connected with this melancholy affair is, that he was alive at two o’clock this afternoon, and in full possession of his reason, and free from pain. (Macmillan, 2000a , p. 12)

A review of the medical notes kept by the John Harlow, the physician who treated Gage immediately after his injury are not fully consistent with this newspaper account, especially with regard to the patient having been “free from pain.” Interestingly, 161 years later in July 2009, the Los Angeles Times published an article titled “A piercing image of Phineas Gage” (Maugh, 2009 ), which described the discovery of “the only known image of legendary brain-injury patient Phineas Gage” in a daguerreotype image. The LA Times account claims that “it [the bar] was successfully removed” and “contemporary accounts suggest that Gage’s personality was dramatically altered because he was disfigured in the accident” (Maugh, 2009 ). Unfortunately, but perhaps not surprisingly, more than a century and a half later the complexities of the case continue to pose challenges.

Phineas Gage, his treating physicians, the witnesses to the accident, and Cavendish, Vermont: the characters and setting of this story are, individually, unremarkable. Yet united by the circumstances of a remarkable event, they have contributed uniquely to the development of neuropsychology and continue to be relevant to modern psychological practice. Gage’s case is a story of the right projectile, at the right speed and the right distance, passing through the right area of the brain, of the right patient, who was treated by the right doctor, at the right time in history (Lewandowski, 2003 ). The result is that his injury, treatment, and long-term recovery continue to lend interest and relevance to contemporary neuroscientists across a broad range of medical and psychological disciplines.

Although birth documentation for Gage is lacking, he was probably born on September 9, 1823, in Lebanon, New Hampshire, and was named after his paternal grandfather. Genealogy records confirm that his father was Jesse Gage and his mother was Hannah Swetland, who married on April 27, 1823. He was the oldest of five children: his siblings Laura and Roswell were born in 1826, Dexter was born in 1831, and Phoebe was born in 1832 (Macmillan, 1986 ).

At the time of the injury Gage was 25 years old, and was described as “a perfectly healthy, strong and active young man” prior to the accident, standing “five feet six inches in height” with an “average weight one hundred and fifty pounds.” He possessed “an iron frame” and a “muscular system unusually well developed,” thus indicating that he was in excellent physical health (Harlow, 1868 , p. 330).

Gage’s premorbid psychological and cognitive status is also portrayed in very positive terms. He was reportedly of “well balanced mind,” and “was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent in executing all his plans of operation.” In addition, he was of “considerable energy of character” (Harlow, 1868 , p. 340), and was regarded by his employers as “the most efficient and capable in their employ” (Harlow, 1868 , p. 399). Harlow observed that Gage possessed “an iron will” and a “nervo bilious temperament” (Harlow, 1868 , p. 330). His use of the term “nervo bilious” is a subtle indicator of phrenology’s influence on Harlow, as bilious (fibrous) and nervous are two of the four phrenological temperaments (Combe, 1830 , pp. 42–34).

Interestingly, Gage is described as having been “untrained in the schools” (Harlow, 1868 , p. 340); however, considering he could read and write (which may have assisted him in securing employment in a supervisory position as a railroad foreman), Macmillan ( 2000a ) suggests that this description refers to a lack of secondary education.

Cavendish past and present

Gage’s accident occurred outside Duttonsville, Vermont, which was a small village in the township of Cavendish, incorporated in 1761 (at present, however, “Cavendish” is the name of both the township and village). It is located east of the Green Mountains range of the Appalachians in Windsor County, approximately 25 miles southeast of Killington, Vermont (Cavendish Connects, n.d.) . As shown in Figure 41.1 , if one were to compare a historical map of Cavendish to a current topographical map, little change would be noted (Chase, 1856 ). The railroad bed that Gage and his construction crew were preparing is located approximately ¾ of a mile south of Main Street and to the east of Depot Street (Macmillan, 2000c ).

To fully appreciate the circumstances leading to Gage’s accident, it behooves one to have some familiarization with the state of transportation in the United States at that time in history. Prior to the development of railways in the early 1800s, the only available methods of travel or transporting goods in the northeast was limited to walking or using horses or pack animals attached to carriages or wagons when roads were available or the terrain permitted. Whereas transportation by steamer, canal boat, or barge offered an alternative, movement was restricted by the location and direction of the river or waterway and still required some land travel at the point of disembarking. As a result, the movement of people and their possessions across land remained very slow, inefficient, and cumbersome until John Stevens, the father of American railroads, sought to improve the speed and efficiency of transportation by proposing a rail line between New York and Lake Erie in 1815 (Winchester, 2014 ), generally following the Erie Canal. Stevens built a steam locomotive that he demonstrated at his New Jersey estate in an attempt to secure funding from local legislators. While he never lived to see this project completed, his efforts proved the viability of railway transportation such that, by the first half of the 1800’s, railroad construction exploded. The meager 20 miles of railroad track that had existed in 1828, expanded to almost 3000 miles by 1836 (Winchester, 2014 ).

Initially railroads were designed to connect major ports and their surrounding communities, but by 1870 rapid expansion resulted in the railroad industry becoming the nation’s second largest employer of men organized by innumerable work crews responsible for preparing the ground and laying track (Winchester, 2014 ). Over time railways developed to connect cities and therefore the ground required preparation by either excavation or filling in low areas. This drive to expand railway transportation to increase the efficiency of commerce is ultimately why Gage and his crew were engaged in the foothills outside of Duttonsville in 1848.

Gage was employed by the Rutland and Burlington railroad as a foreman of a construction crew. At the time of the accident he and his crew were excavating rock approximately ¾ mile southeast of Duttonsville in order to prepare the ground for track. This task, on its surface, seems relatively simple: Gage and his crew drilled holes in the to-be-excavated rock and filled those holes with gunpowder. The charges were then detonated, and the fragmented rock could be removed or placed in low-lying areas to level the grade. However, with the inherent risks in excavating rock by using explosives and the rudimentary equipment available, the danger and complexity of this type of work should not be underestimated. In order to fully grasp the planning, organization, and complexity required of Gage to execute these tasks, a cursory understanding of drilling and blasting with 19th century technology is necessary.

In the 1800s the method for drilling blasting holes in solid rock involved the use of a team of men working in close proximity and in concert to strike an iron drill bit with sledge hammers. One member of the gang was assigned the position of holding a drill bit, while one or two other members of the crew struck the head of the bit with a hammer. The force of the blow drove the bit into the rock, and the worker holding the bit turned it with each blow. The accrued rock dust was then removed by pouring small amounts of water into the hole to create a mud that stuck to the bit and was periodically removed by tapping the bit against a rock or wiping it clean with the worker’s hand. The bit was then replaced in the hole and the process continued, substituting bits of greater length as the hole deepened.

One can only speculate as to the skill and precision required of Gage and his crew as his men alternated hammer blows in a rhythmic manner, while one turned the bit with one or both hands. Holes approximately 2 yards deep could be bored into granite in about 5 to 6 hours, and several holes would be “drilled” across the area of rock to be excavated. Once the rock was loosened by the blast, a derrick crane and boom were used to load the rock onto animal- drawn carts for removal or placement into low-lying areas to level the ground for the rails (Lynch & Rowland, 2005 ).

After drilling, holes were packed with explosive powder. While some Gage citations have suggested the use of dynamite or blasting powder, the process of removing rock in the early 1800s involved the use of black powder. Dynamite was not yet invented and would not be available until Alfred Nobel introduced it to the United States in 1868 (Schuck & Sohlman, 1929 , p. 101).

Blasting powder uses detonation from the Latin word “de-tonare,” meaning to (expend) thunder, and therefore creates a supersonic combustion through shock compression that splits rock. In contrast, black powder, more commonly known as gunpowder, occurs through deflagration from the Latin word “de-flagrare,” meaning to burn down. The combination of heat and gas result in an effective propellant, as was the case in Gage’s tamping iron. As a result, black powder creates a subsonic combustion that occurs through thermal conductivity that heaves rock (Lynch, 2002 , p. 168).

Black powder is an inherently unstable chemical that combines proportionate measures of sulphur, potassium nitrate (saltpeter) and charcoal. While sulphur and charcoal act as the fuel, saltpeter acts as an oxidizer (Lynch, 2002 ). Its advantage (and danger) lies in the fact that it is relatively easy to ignite. A small spark is sufficient to set it off, as can be seen in the use of muzzle-loading weapons that use either flint or a percussion cap to ignite the powder packed into a breech. The force of the blast depends on a number of variables that include the amount of powder, the size of the grains, and the pressure under which the blast is initiated. Pressure and combustion are obtained by the ratio of fuel to the oxidizing agent and how tightly the powder is packed into a receptacle such as the breech of a gun, or in this case, the hole that Gage was drilling into solid rock (Krehl, 2009 ).

Blasting rock is done by placing black powder into a deep hole of fairly narrow diameter with a fuse positioned to the same depth. The fuse is then trailed onto the ground and of sufficient length to allow the person who ignites the fuse time to move a safe distance away. Layered in the hole on top of the black powder is a collection of aggregate such as sand or soft clay. Sand was commonly used because it is a readily available, easily obtainable, inexpensive, and can be compacted tightly to fill up the small spaces in a hole. As a result, pressure is created by trapping expanding gases, thus leading to combustion sufficient to heave rock (Ihlseng & Wilson, 1907 ). The process of drilling and tamping is demonstrated in Figure 41.2 .

Drilling blasting holes

Another variable that added to the danger of Gage’s work was the fuse. In the early 1800s fuses were known as “coils” or “quills” and were hand made by filling quills or straw with black powder, by covering lengths of hemp of varying thickness with tar and black powder, or by wrapping hemp around a core of powder-filled straw and coating the resulting fuse in tar to protect it from moisture (U.S. Department of the Army, 1984 ). Because of variability in their individual manufacture, fuses lacked uniformity and it was difficult to estimate their burn rate. Safety fuses were not introduced to civil engineering until 1831 when William Bickford introduced a half-inch “coil” to the British mining industry. Safety fused were probably uncommon among railroad workers in America at the time of Gage’s accident (Smith, 1909 , pp. 112–117).

Given the instability of black powder combined with the unreliable fuses, it is easy to see the inherent danger in Gage’s work during a period when explosives technology was in its infancy. At the time of Gage’s accident, railroading in general was a very dangerous profession. Although railroad worker fatalities were not reliably documented until the late 1800s, Aldrich ( 2006 ) found that nearly 4000 workers were killed in 1845 as a result of various railroad construction accidents, although the actual deaths were likely to have been higher than recorded.

The missile that caused the injury was an iron bar measuring 3 feet 7 inches long and weighing 13 ¼ pounds (shown in Figure 41.3 ). It is described as a “tamping iron,” named for its purpose. A tamper is a device used to compact or flatten aggregate to increase compression. Gage’s iron was used to “tamp” or pack down the loose sand that was placed on top of black powder during the process of blasting rock.

The terms “tamper” and “tamping” are derived from the Middle English “tampion,” which is a type of plug placed in a gun or cannon muzzle in order to protect it from dirt or moisture in the environment. “Tampion” itself may be a borrowing from Old French “tapon,” which referred to a piece of cloth used for plugging a hole (Tamp, n.d.) .

Tamping refers to the use of a “tamper” or, as in Gage’s work, a tool designed to compress aggregate. Typically, sand is placed over explosive powder and packed tightly in order to increase compression of gases to render a more powerful blast. In his 1850 publication, Bigelow describes that the iron was “forged by a neighboring blacksmith” and that it was “unlike any other having been made to please the fancy of the owner” (p. 14), indicating that Gage probably had his tamping iron custom made.

Gage’s tamping iron

An inspection of the tamping iron reveals that it is about 1¼ inch in diameter and roughly speaking the width of a common broom or mop handle. The texture is smooth and one end of the bar is gradually shaped to a point (Lewandowski, 2001 ). This is this end that was propelled into Gage’s lower left face and through his head.

It may be questioned as to why the bar was designed to be pointed at one end, when its primary purpose was packing aggregate. Tools, and particularly farm implements, are most often designed to serve multiple purposes. Consider a hammer that is designed to drive as well as remove nails, or a wrench with both open and closed ends). It is not unreasonable to assume that Gage instructed the blacksmith who forged the tamping iron to shape the end to a gradual point, as was common among miners, who often referred to this type of tool as a “needle” (Lewandowski, 2003 ). The tapered shape allowed for the tool to be used for holes of different diameters, for shaping a hole, or as a wedge or lever that could be used for dislodging split rock (Ihlseng & Wilson, 1907 ).

The Accident Site

Navigating to the accident site from the center of modern-day Cavendish would involve traveling down Main Street until Depot Street is reached, and then following Depot Street to the south. A set of railroad tracks will be encountered. The accident occurred east of this area near the first bend of the track heading to the south (Lewandowski, 1998 ; Macmillan, 2000c ; Pate, 1999 ).

More important than the exact site of the accident, which is not precisely known, is the topography of the immediate area (Lewandowski, 2001 ). The railroad bed where Gage was injured is nested in a corridor between two vertical walls of rock of about 30 feet in height and of considerable length (as shown in Figure 41.4 ).

Railroad track and rock near the accident site

The Accident

Gage’s accident occurred on September 13, 1848 at approximately 4:30 in the afternoon. The account is well documented by John Harlow, the local physician who treated Gage, and to whom it can be assumed Gage provided details during his period of recovery. Harlow ( 1868 ) recounts the accident as follows:

He was engaged in charging a hole drilled in the rock, for the purpose of blasting, sitting at the time upon a shelf of rock above the hole. His men were engaged in the pit, a few feet behind him, loading rock upon a platform car, with a derrick. The powder and fuse had been adjusted in the hole, and he was in the act of ‘tamping it in,’ as it was called, previous to pouring the sand. While doing this, his attention was attracted by his men in the pit behind him. Averting his head and looking over his right shoulder, at the same instant dropping the iron upon the charge, it struck fire upon the rock, and the explosion followed, which projected the iron obliquely upwards, in a line of its axis, passing completely through his head, and high into the air, falling to the ground several rods behind him, where it was afterwards picked up by his men, smeared with blood and brain. The missile entered by is pointed end, the left side of the face, immediately anterior to the angle of the lower jaw and passing obliquely upwards, and obliquely backwards, emerged in the median line, at the back part of the frontal bone, near the coronal suture. (Harlow, 1868 , p. 331)

After the accident Gage reportedly suffered “a few convulsive motions of the extremities,” but was soon conscious and able to speak (p. 331). Astonishingly there are no reports of Gage having lost consciousness or experiencing post-traumatic amnesia. His men carried him approximately 10 yards to the road where he was placed in a sitting position in a cart and transported about ¾ of a mile to Adams’s Inn. Gage left the cart with only a little assistance from bystanders and made his way to a chair on the porch where he awaited medical assistance from the local physician. During this time documents support that he remained alert and oriented.

Eyewitness Accounts

One of the first witnesses to Gage’s condition after the accident was Joseph Adams, the proprietor of the local tavern where some of the railway workers boarded. This is the hotel to which witnesses refer and where Gage was taken after the injury. In addition to being the local tavern owner, Adams was also the local Justice of the Peace who provided an affidavit for Harlow at the request of Henry Bigelow who also examined Gage months after the accident (Bigelow, 1850 ).

It is understandable that many did not believe that a person could survive such a devastating injury and therefore his public position and testimony lent credibility in the subsequent documentation. The notification of a local cabinet maker named Winslow who owned a shop about four buildings down from the tavern provides a good example. Winslow was told of the accident and subsequently measured Gage in order to begin work on a coffin for his anticipated death (Macmillan, 2000a ).

In his affidavit Adams testifies as follows:

This is to certify that P.P. Gage had boarded in my house for several weeks previous to his being injured upon the railroad, and that I saw him and conversed with him soon after the accident, and am of opinion that he was perfectly conscious of what was passing around him. He rode to the house, three-quarters of a mile, sitting in a cart, and walked from the cart into the piazza, and thence upstairs, with but little assistance. I noticed the state of the left eye, and know, from experiment, that he could see with it for several days though not distinctly. In regard to the elevated appearance of the wound, and the introduction of the finger into it, I can fully confirm the certificate of my nephew, Washington Adams, and others, and would add that I repeatedly saw him eject matter from the mouth similar in appearance to that discharged from the head. (Bigelow, 1850 , p. 14)

Adams, along with others, presented a compelling picture of Gage’s physical condition immediately after the injury. In addition, he must have recognized the importance of the tool, as he went searching for the bar the following day:

The morning subsequent to the accident I went in quest of the bar, and found it at a smith’s shop, near the pit in which he was engaged. The men in his pit asserted that ‘they found the iron, covered with blood and brains,’ several rods behind where Mr. Gage stood, and that they washed it in the brook, and returned it with the other tools; which representation was fully corroborated by the greasy feel and look of the iron, and the fragments of the brain which I saw upon the rock where it fell (Bigelow, 1850 , pp. 14–15).

A second and equally important witness was a local Protestant minister who observed Gage as he was taken out of the cart and assisted onto a porch chair. Reverend Joseph Freeman spoke with Gage, discussed the incident with some of his crew, and inspected the accident site and the tamping tool that was taken to the blacksmith’s shop. Because of his position in the community, Reverend Freeman also provided an affidavit and further verified the facts of the incident. On December 14, 1849 he testified as follows:

I was home on the day Mr. Gage was hurt; and seeing an Irishman ride rapidly up to your door, I stepped over to ascertain the cause, and then went immediately to meet those who I was informed were bringing him to our village. I found him in a cart, sitting up without aid, with his back against the fore board. When we reached his quarters, he rose to his feet without aid, and walked quick, though with an unsteady step, to the hind end of the cart, when two of his men came forward and aided him out, and walked with him, supporting him to the house. I then asked his men how he came to be hurt? The reply was, ‘The blast went off when he was tamping it, and the tamping-iron passed through his head.’ I said, ‘That is impossible.’ Soon after this, I went to the place where the accident happened. As I came up to them, they pointed me to the iron, which has since attracted so much attention, standing outside the shop-door. They said they found it covered with brains and dirt, and had washed it in the brook. The appearance of the iron corresponded with this story. It had a greasy appearance, and was so to the touch. (Bigelow, 1850 , p. 15)

Dr. Edward Williams, who spoke with Gage and collaborated with Harlow immediately after Gage’s injury, also provided an affidavit. In a letter dated December 4, 1849, from his home in Northfield, Vermont he wrote:

Dr. Bigelow: Dear Sir—Dr. Harlow having requested me to transmit to you a description of the appearance of Mr. Gage at the time I first saw him after the accident, which happened to him in September 1848, I now hasten to do so with pleasure. Dr. Harlow being absent at the time of the accident, I was sent for, and was the first physician who saw Mr. G., some twenty-five or thirty minutes after he received the injury; he at that time was sitting in a chair upon the piazza of Mr. Adams’s hotel, in Cavendish. (Bigelow, 1850 , pp. 14–16)

Williams’s contribution was in detailing Gage’s appearance and his examination findings.

First Responder

Dr. John Harlow, the physician best known for his treatment of Gage, was not immediately available when Gage was brought to Adams’s Inn. As a result, Dr. Edward Higginson Williams, another local physician, was summoned in his stead, and it was Williams who was the first to evaluate Gage’s injury and render immediate assistance. In a sense, he was ex post facto the emergency physician who first attended Gage, and the portico of the Adams’s Inn was his de facto emergency and trauma bay where he began his assessment.

Williams was a twenty-four-year-old graduate of Vermont Medical School when he attended to Gage. His obituary in the New York Times , appearing in December 1899, notes that he practiced as a physician for only a short period of time before he left medicine to work in the railroad industry, eventually securing part ownership of the Baldwin Locomotive Works (New York Times, 1899 ). Although a young physician at the time he treated Gage, he had sufficient medical experience to begin addressing the penetrating head wound, verify the presenting history and mechanism by which the injury occurred, confirm the symptoms, and do what he could to stabilize the patient until Harlow arrived.

Most students of psychology, neuroscience, and medicine are very familiar with the quotation attributed to Gage’s family and friends that, “He was no longer Gage” (Harlow, 1868 ); however, Williams provides a quote from Gage himself that, while lesser-known, is equally compelling. Consider the circumstances under which he and Gage were introduced: the patient had just suffered a horrific injury that should have killed him. He was then transported back to town on an oxcart three quarters of a mile to a local tavern where he sat in a chair on a veranda waiting for half an hour for a physician to arrive. When Dr. Williams arrived in his carriage, Gage addressed him. Williams recalled, “When I drove up he said, ‘ Doctor, here is business enough for you .’ ” This simple statement by Gage confirms his self-reliant character and offers marvelous insight into his personality.

Dr. Williams’ comments about Gage’s injuries suggest that he was in disbelief of the circumstances of the injury. He was decisively convinced following a personal examination in addition to the confirmatory comments of the railroad crew members who were present at the time of the accident (Figure 41.5 ):

I first noticed the wound upon the head before I alighted from my carriage the pulsations of the brain being very distinct; there was also an appearance which before I examined the head, I could not account for: the top of the head appeared somewhat like an inverted funnel; this was owing, I discovered, to the bone being fractured about the opening for a distance of about two inches in every direction. I ought to have mentioned above that the opening through the skull and integuments was not far from one and a half inch in diameter; the edges of this opening were everted and the whole wound appeared as if some wedge-shaped body had passed from below upward. (Bigelow, 1850 , p. 16)

Williams’ initial observations of Gage’s behavior may be of interest to neurological clinicians. Recall that his examination took place within an hour of the traumatic brain injury. Gage was probably in shock, but had not yet succumbed to infection, hence delirium had not yet set in. Retrospectively, Williams’s interactions with Gage provide behavioral observations that could be considered a rudimentary mental status examination. He was able to establish that Gage was oriented to person, place, time, and purpose. In addition, Williams’s observations of visual, verbal, and motor responding, which are supported by affidavits, establish that Gage’s eyes were open, he conversed normally, and he obeyed commands. By today’s emergency and trauma standards for head injury evaluation, one could speculate that Gage demonstrated a normal Glasgow Coma Scale score of 15 (Teasdale & Jennett, 1974 ), which would lend some support to a positive outcome from his traumatic brain injury.

Gage’s skull

Williams continues:

At the time I was examining this wound, he was relating the manner in which he was injured to the bystanders; he talked so rationally and was so willing to answer questions, that I directed my inquiries to him in preference to the men who were with him at the time of the accident and who were standing about at this time. Mr. G. then related to me some of the circumstances as he has since done; and I can safely say that neither at that time nor any subsequent occasion, save once, did I consider him to be other than perfectly rational. The one time to which I allude was about a fortnight after the accident, and then he persisted in calling me John Kirwin; yet he answered all my questions correctly.

Despite being the first physician to directly assess Gage’s injury, Williams nonetheless remained skeptical. In an affidavit to Bigelow he reported:

I did not believe Mr. Gage’s statement at that time, but thought he was deceived; I asked him where the bar entered, and he pointed to the wound on his cheek, which I had not before discovered; this was a slit running from the angle of the jaw forward about one and a half inch; it was very much stretched laterally, and was discolored by powder and iron rust, or at least appeared so. Mr. Gage persisted in saying that the bar went through his head.

The Treating Physician

Dr. John Martyn Harlow arrived at Adams’s Inn at approximately 6 p.m., and was clearly taken by Gage’s presentation: “the picture presented was, to one unaccustomed to military surgery, truly terrific; but the patient bore his sufferings with the most heroic firmness.” At that point both physicians combined their medical skill to stabilize Gage’s condition. He walked up a flight of stairs to an upper bedroom “with a little assistance” (Harlow, 1848 , p. 390) and was placed in a bed so that Harlow could begin a more detailed examination. In this sense, Harlow actions were similar to those of a modern-day trauma surgeon.

Harlow found Gage’s wound so significant and complete that he “passed in the index finger its whole length without the least resistance, in the direction of the wound in the cheek, which received the other finger in like manner” (Harlow, 1848 , p. 390). Although this procedure may seem alarming by modern standards, it should be recalled that at the time, an understanding of pathogens and infectious disease (germ theory) was not yet commonplace in American medicine. In fact, many physicians educated in the 19th century continued to debate the Miasma theory of disease transmission (Halliday, 2001 ; Last, 2007 ). Consider that Lister’s use of phenol in aseptic surgical techniques would not be introduced until 1867 and not widely accepted into clinical practice until the late 1800s (Greenwood, 1998 ; Lister, 1867 , 1868 ).

While Harlow and Williams dressed the wound, Gage’s behavior was compliant and cooperative, and he was “perfectly conscious, answering all questions, and calling his friends by name as they came into the room.” At the same time, however, he was observed to be losing a significant amount of blood “both externally and internally,” vomited several times, and began to fatigue. Gage’s pulse was weak at 60, but Harlow does not report where he palpated his patient. Harlow reports that “he was getting exhausted from the hemorrhage, which was very perfuse both exterally [sic] and internally, the blood finding its way into the stomach, which rejected it as often as every 15 or 20 minutes.” The blood loss was clearly significant, as Harlow reports that, “His person, and the bed on which he was laid, were literally one gore of blood” (p. 390). Given this description, it seems likely that the effects of hypovolemic shock were occurring as Gage’s hemoglobin was decreasing.

Williams and Harlow then shaved Gage’s head, removed the dried blood and a very small sharp piece of bone, and resected “a portion of the brain which hung by a pedicle” (p. 390). Larger pieces of the frontal bone were replaced as close to their original position as possible, the scalp was closed with “adhesive straps,” and a compression dressing was applied, over which they placed a night cap. This concluded the initial resuscitation and stabilization of the patient, and, in a cursory sense, it was not too dissimilar to that of contemporary protocols exercised by emergency room physicians and trauma surgeons.

Historically, injuries to the brain were more often than not fatal due to the trauma itself, intracerebral infection, and herniation from increased intracranial pressure, blood loss, etc. (Bollet, 2002 ; Cronyn, 1871 ; Karger, Sudhues, & Brinkmann, 2001 ). It was not until Percivall Pott’s publication of Observations on the nature and consequences of those injuries to which the head is liable from external violence in 1768 that physicians would be offered clear guidance on the medical management of acceleration and deceleration head injuries, not just injury to the skull, but to the treatment of the brain (Pott, 1768 ). Pott addressed cerebral contusions, skull fractures, concussions, and the management of pus (McCrory, 2001 ), and his writings were recognized in the 19th century as revolutionary in the treatment of head wounds (Butler, 1851 , p. 99). Thus, his medical treatises would have been well known to Harlow’s professors at Jefferson Medical College.

Interestingly, in his report, Harlow is somewhat defensive when he addresses the issue of “probing” the brain, noting that he had later been questioned as to why he did not do so. He presents his rationale as follows: “I think no surgeon of discretion would have upheld me in the trial of such a foolhardy experiment, in the risk of disturbing lacerated vessels from which the hemorrhage was near being staunched [sic], and thereby rupturing the attenuated thread, by which the sufferer still held life” (Bigelow, 1850 , p. 17; Harlow, 1848 , p. 390).

Probes in the 19th century were essentially long stiff metal wires with porcelain tips used to extract skull and bone fragments from the brain after penetrating head injuries. Such an instrument was used by US Surgeon General Dr. Joseph Barnes, who attended to President Lincoln after his assassination. Accompanying Barnes were Lincoln’s personal civilian physician, Dr. Robert Stone, and other US Army physicians who included Dr. Anderson Abbott, the first African-Canadian doctor, and Dr. Charles Crane, Assistant Surgeon General. As the ranking officer, Barnes directed the trauma treatment and, with the assistance of U.S. Army surgeon Dr. Charles Leale, probed Lincoln’s brain first with his (nonsterile) fingers and then with a Nelaton probe. Given the absence of modern neuroimaging, the use of a probe was judged necessary to discern the location and trajectory of the bullet (Trunkey & Farjah, 2005 , pp. 977–978). This porcelain tipped medical instrument was used to explore the wound and break blood clots, which likely increased the loss of blood and in doing so may have expedited Lincoln’s death (Bollet, 2002 ; Trunkey and Farjah, 2005 ). (An excellent example of this type of probe can be found on display at the Armed Forces Institute of Pathology museum in Washington, D.C., which displays the actual probe Barnes and Leale used, alongside fragments of the President’s skull and the 41 caliber lead ball fired from Booth’s derringer.)

Harlow’s treatment of Gage was guided by having been taught to avoid probing a brain (Harlow, 1848 , p. 390). In his medical education at Jefferson Medical College in Philadelphia (now Thomas Jefferson University) he had the benefit of being trained by several famous faculty members who historically have been referred to as the “faculty of ‘41” (Aptowicz, 2014 , p. 83; Elliot, 1911 ; Macmillan, 2001 ).

One of Harlow’s professors was Thomas Dent Mutter, a pioneer of reconstructive surgery, who was known for advocating for antiseptic techniques, replacing bone fragments, allowing for wound drainage, treating with purgatives and cathartics, and never probing. His influence is clearly seen in Harlow’s detailed description of his treatment of Gage (Harris, 1994 ). Further medical insight pertinent to this particular type of injury came from Professor Joseph Pancoast. Pancoast is still well known to surgeons today, and, like Mutter, he pioneered a number of procedures particularly with early reconstructive techniques. He authored A Treatise on Operative Surgery (Pancoast, 1844 ) in which he addresses the treatment of intracerebral pus, and chaired both the Departments of Surgery and Anatomy (Radbill, 1986 ). Lastly, Professor Robley Dunglison was Thomas Jefferson’s private physician who immigrated from England to establish the medical school at the University of Virginia (Gemmill, 1972 ). He published books on health, hygiene, morals, and intellect (Dunglison, 1835 ); human physiology and the history of medicine; and the medicinal use of marijuana (Dunglison, 1846 , p. 153). Known as the father of American Physiology (The National Cyclopaedia of American Biography, 1909, p. 270) Dunglison chaired Jefferson Medical College’s Department of Medicine and was best known for his publication Human Physiology , in which he addressed human temperament and idiosyncrasies, individual and cultural differences, and phrenology (Dunglison, 1832 , pp. 445–479). In addition to these accomplishments, perhaps equally important to Gage’s survival were his extensive prescriptions for multiple medical conditions (Dunglison, 1846 , 1833 ).

Harlow’s Physical Medicine and Rehabilitation

From the time of his arrival at bedside about 6 p.m. on Wednesday, September 13 until Saturday, November 18, 1848, Harlow made detailed observations of his treatment (Bigelow, 1850 , 1900 ; Harlow, 1848 , 1868 ). A review of his medical record indicates that he managed Gage’s medical trauma in a manner commensurate with prevailing medical practice and is rightfully credited with Gage’s stabilization and ultimate recovery. In addition, however, the circumstances of Gage’s wound and his preinjury status may have contributed to his survival. As the noted neurologist Charles Symonds declared, “It is not only the kind of injury that matters, but the kind of head” (Richardson, 2013 , p. 168).

Both Bigelow and Harlow report in some detail about Gage’s pre-injury status (Bigelow, 1850 , 1900 ; Harlow, 1848 , 1868 ), as this was pertinent in their discussion of his subsequent survival and later changes in demeanor. Recall that Gage was described by those who knew him as healthy, strong, active, muscular, physically well developed, shrewd, and intelligent. One can assume, then, that Gage’s premorbid physical and mental condition was not complicated by any significant known or documented premorbid disease, insults, or injuries. This is entirely consistent with Harlow’s ( 1868 ) report that Gage “had scarcely a day’s illness from his childhood to the date of this injury (p. 330). As a result, Gage’s state of health at the time the accident likely contributed positively to his chances of recovery.

A second variable that has not been previously discussed is the effects of the skull fracture that occurred as the tamping iron exited Gage’s cranium. It is very likely that Harlow’s efforts to stabilize his patient were inadvertently aided by the shattering of his skull resulting in a de facto decompressive craniectomy.

A decompressive craniectomy is a neurosurgical procedure sometimes employed in cases of severe brain trauma to allow for brain expansion where swelling occurs as the result of increased intracranial pressure within the skull vault. If left untreated, the interruption of the autoregulation of normal cerebral blood flow can result in increased cerebral perfusion pressure causing marked intracranial edema and ultimately leading to herniation and death (Aarabi et al., 2006 ; Reitan & Wolfson, 1986 ). The energy expended from the acceleration force drove the iron under Gage’s zygomatic arch, through the brain and dura, and exited the calvarium, resulting in bone loss that in turn, allowed for a natural expansion of the brain. Although Harlow and Williams replaced the pieces of bone available, all of the fragments were not recovered and part of the exit wound remained uncovered. This is apparent when examining any photograph or drawing of the skull or when viewing Gage’s life mask. Harlow ( 1868 ) observed that, “The fragments of bone being lifted up, the brain protruding from the opening and hanging in shreds upon the hair, it was evident that the opening in the skull was occasioned by some force acting from below.” He specifically describes how the frontal bone “was extensively fractured, leaving an irregular oblong opening in the skull of two by three and one-half inches” and goes on to report that “the pulsations of the brain were distinctly seen and felt” (p. 332).

After dressing the wound with Williams, Harlow stayed with Gage until 10 p.m., noting that “sensorial powers remain as yet unimpaired” (p. 391). Gage remained fully oriented as evidenced by his ability to name his friends and their residences. His unfaltering and committed character is reflected in his statement to Harlow that he expected to return to work in one or two days, even though he continued to hemorrhage for the next 48 hours.

The next morning Gage’s face became quite swollen and, although in pain, he was able to speak and was noted to be rational. Day two post injury (the 15th) his hemorrhaging stopped, but he began to show signs of delirium and was observed to be “disconnected and incoherent.” At this point Harlow recorded a prescription of “vin. Colchicum ℥ 3 ss every six hours until it purges him” (p. 391). Following the Apothecaries’ system of pharmacy common to 19th century United States at that time (Hasegawa, 2006 ), Harlow administered one half dram, or about 2 ml of colchicine, which in high doses is a toxic alkaloid derived from the corms of the autumn crocus (Colchicum autumnale). This flower extract was frequently used by physicians at that time for its pain-relieving, sedative, and anti-inflammatory properties. In small to moderate doses it produces gastrointestinal side effects that can be used as a sedative, cathartic, diuretic, and emetic (Kyle, et al., 1997 ; Rodnan & Benedek, 1970 ). Because its side effects include gastrointestinal movement, Harlow used it to induce bowel evacuation.

Day three post injury Harlow ( 1848 ) reported a discharge of foul smelling and thin watery pus intermixed with brain material and a fungus at the outside corner where the upper and lower eyelids of the left (injured) eye meet. Gage described the feeling of the left side of his head as “banked up” (p. 391) and had not yet had a bowel movement. Harlow applied ice water to Gage’s eye and head to address the inflammation and prescribed “sulph. magnesia ℥, repeated every four hours until it operates” (p. 391), hence an ounce of magnesium sulfate that was used as a laxative to initiate bowel motility.

Day four post injury, Harlow ( 1848 ) recorded the success of the laxative, noting that Gage “purged freely,” experienced some remission from his delirium, and that he was “rational and knows his friends.” While his facial wounds were healing, Gage’s abscess increased in volume, became foul smelling, and was described by Harlow as “very foetid and sanous” (p. 391).

Day five post injury Harlow ( 1848 ) observed that Gage slept throughout the night and showed preference for lying on his right side, probably because of pain and discomfort. His tongue was described as “red and dry” and his breath as “foetid,” suggesting probable dehydration. Harlow’s interventions that day included probing the skull at its base “without giving pain,” prescribing a cathartic “which operated freely,” and applying cold to the wound. While Gage remained psychologically optimistic and reported to Harlow that “he shall recover,” he continued to experience delirium marked by periods of coherence (p. 391).

Day six through day eight post injury, Gage’s mental and physical condition remained compromised but stable. Harlow ( 1848 ) recorded symptoms of restlessness, dry hot skin, red tongue, and excessive thirst over these three days, as well as impaired mental status marked by “talking incoherently with himself, and directing his men” (p. 391). By this description, Gage clearly continued to suffer from acute confusion, ongoing infection, and dehydration.

Gage’s impaired mental status continued through the morning of the 9th day post injury when he reported “he shall not live long.” His physical agitation and behavioral noncompliance now complicated the clinical picture as evidenced by Harlow’s ( 1848 ) description that his patient “Throws his hands and feet about, and tries to get out of bed.” Harlow described fever (“head hot”) and prescribed “a cathartic of calomel and rhubarb, to be followed by castor oil, if it does not operate in six hours” (p. 391).

Harlow’s use of medications to regularly purge Gage was consistent with 19th century “heroic medicine.” This philosophy advocated alleviating nerve and blood overstimulation that were assumed to cause all disease. Common treatments to restore health included blistering, bloodletting, vomiting, and purging (Duffy, 1990 ; Stavrakis, 1997 ). Harlow’s choice of Calomel is understandable as it was a commonly prescribed therapeutic in the 1800s. In its pharmaceutical form, it is an odorless powder that was commonly prescribed for internal use to treat multiple medical conditions such as constipation, infectious disease, fever, cholera, pleurisy, dropsy, gout, worms, and eclampsia (Weatherall, 2006 ). Externally its use was intended as a disinfectant to treat smallpox sores, syphilitic ulcers, and warts (Risse, 1973 ). Calomel is mercury chloride and therefore is no longer used as a therapeutic agent. Consistent with standards of practice at that time, Harlow used it with Gage in small does as a stool softener and laxative, and in larger does as a purgative.

For the next 11 days (Saturday September 23 through Tuesday October 3) Harlow’s records indicate that Gage remained semi-comatose, “seldom speaking unless spoken to, and then answering only in monosyllables” and that he lost vision in his injured eye (p. 392). Harlow treated the fungal brain and orbit abscess with cold compresses to the head and silver nitrate. Prior to the advent of modern antibiotics, silver nitrate was used medicinally as an antimicrobial. It can be assumed that Harlow applied the antiseptic to Gage’s wounds to treat the infection and prevent sepsis and further tissue decomposition. Gage’s dressings were changed every 8 hours and laxatives were administered regularly. Nevertheless, during this time an infection occurred in the occipitofrontalis muscle that Harlow punctured to drain about 8 ounces of pus.

Twenty-two through 24 days post injury Harlow observed wound discharge, which he referred to as “laudable pus” (p. 392), which, at the time, was thought to be associated with healing (Alexander, 1985 ). Gage’s improvement was also evidence by his ability to raise his head. During this time Harlow also prescribed that Gage sit up at bedside for five minutes at a time before returning to bed, a practice not dissimilar from modern rehabilitation methods used on intensive care units.

Twenty-eight days post injury Harlow recorded Gage’s responses to that which constituted brief mental status questions. While he had already documented that Gage was oriented to person, he was now able to establish orientation to place, time, and purpose. That is, when asked about the date of injury, Gage confirmed accurately that the accident occurred “four weeks this afternoon at 4 ½ o’clock” (p. 392). Given the severity of the brain trauma, the contemporary neuropsychologist or physician might assume significant anterograde and retrograde amnesia. Surprisingly, this was not the case, as Gage was able to recall how the accident took place and his transport to Adam’s Inn. In addition, he kept an accurate account of the day and recognized most of his visitors. In fact, Harlow described Gage’s memory as being “perfect as ever.” However, Gage is also described as being unable to perform some simple activities of daily living, which included estimating “size or money” or “exchanging $1000 for a few pebbles” (p. 392), suggesting limitations to executive reasoning. In contrast, his physical condition showed progressive improvement as the abscess in the posterior part of his mouth continued to diminish with the topical use of silver nitrate.

At thirty-seven days post injury Gage was able to get out of bed independently and sit up at bedside for 30 minutes at a time; however, he was noted to be “very childish” and asked Harlow to allow him to return to his home in New Hampshire. Considering his physical condition, his request probably reflected an early indication of his lack of insight. Two months after the injury on November 8, Gage was no longer confined to his bed. Harlow kept him on a “low diet” and noted normal appetite, sleep, digestive, and bowel patterns. Gage’s increased physical activity included sitting up “most of the time during the day,” ambulating about the stairs and porch of Adams’s Inn, and walking in the street. Given his apparent stable mental and physical status, Harlow left for a week and instructed his patient “to avoid excitement and exposure” (p. 392).

In spite of his directives, when Harlow returned a week later he was told that Gage was reportedly “in the street every day except Sunday” and that “his desire to be out and to go home to Lebanon has been uncontrollable by his friends, and he has been making arrangements to that effect” (p. 392). At one point, Gage walked half a mile to a store in the cold wet weather without benefit of a coat or proper footwear. When Harlow checked on him, Gage was in bed and described as “depressed and very irritable” with “hot and dry skin,” thirsty, constipated, and complained of stabbing pain on the left side of his face. Harlow’s use of the term “rigors” suggests that Gage’s symptoms included high fever, cold, sweating, and shivering. His treatment included a cold compress to treat the fever and prescribing a “black dose” every six hours. This historical pharmaceutical was compounded by combining elixir of senna (black figs), currants, coriander, and cream of tartar every six hours as a remedy for constipation (Beringer & Griffith, 1921 ). Of equal interest to Harlow was a needle-like piece of bone in the back of Gage’s mouth that he ejected “within a few days” (Harlow, 1848 , p. 393).

The following day, Gage’s physical condition had not improved much. As a result, Harlow appears to have become more aggressive in his treatment, bleeding him about 16 ounces and prescribing 650 mg of calomel, 130 mg of ipecac, and a dose of castor oil. He notes that Gage responded to this intervention and in the evening added 195 mg of “r. Antim. Et potassa tart” (tartar emetic) and 180 ml of simple syrup administered every four hours, likely to address the fever.

Over the next two days, between November 17 and 18, Gage reported “feeling better in every respect.” He was now nine weeks and two days’ post injury, without head pain, and able to ambulate. As a result, Harlow perceived him medically stable, although he clearly had reservations regarding Gage’s psychological condition, as evidenced by his final entry into the medical record that Gage “appears to be in a way of recovering if he can be controlled ” (emphasis added; Harlow, 1848 , p. 393). Harlow provided additional behavioral observations on Gage’s change in mental status in his republication of the case in 1868. However, of particular interest to neuropsychologists is that he signed off in the medical record by noting, “I think the case presents one fact of great interest to the practical surgeon, and, taken as a whole, is exceedingly interesting to the enlightened physiologist and intellectual philosopher ” (emphasis added; Harlow, 1848 , p. 393).

Status Post Discharge

Harlow ( 1868 ) ended his acute care on November 18, which was two months and ten days’ post injury. His last entry into the medical record suggests that his patient was sufficiently physically recovered. Having been released from Harlow’s care, Gage returned to his home in Lebanon, New Hampshire on November 25.

The following week, Harlow traveled the 30 miles for a home visit to Gage and “found him going on well” (p. 338). He also notes a recheck on January 1, now almost 16 weeks after the injury from which Harlow concluded further healing, noting “the opening in the top of his head was entirely closed, and the brain shut out from view, though every pulsation could be distinctly seen and felt” (Harlow, 1868 , p. 338).

Gage remained at home in New Hampshire over the next 12 weeks and continued to recover throughout the winter months. Harlow ( 1868 ) documents that in the spring, he returned to Cavendish and applied for his previous position as a foreman but was not afforded reemployment due to the significant change in his behavior and comportment. Given the convenience of his return, Harlow took the opportunity to reexamine his patient.

Harlow’s Reexamination

Upon his return to Cavendish, Gage was about seven months into his recovery. Harlow’s assessment included observations of Gage’s appearance, physical findings, and behavior, with inferences about his psychological functioning that retrospectively constitute a fairly thorough examination of his physical, behavioral, and psychological status.

Harlow described Gage’s physical status as generally normal, noting the following:

General appearance good; stands quite erect, with his head inclined slightly towards the right side; his gait in walking is steady; his movements rapid, and easily executed. The left side of the face is wider than the right side, the left malar bone being more prominent than its fellow. There is a linear cicatrix near the angle of the lower jaw, an inch in length. Ptosis of the left eyelid; the globe considerably more prominent than its fellow, but not as large as when I last saw him. Can adduct and depress the globe, but cannot move it in other directions; vision lost. A linear cicatrix, length two and one-half inches, from the nasal protuberance to the anterior considerably more prominent than its fellow, but not as large as when I last saw him. Can adduct and depress the globe, but cannot move it in other directions; vision lost. A linear cicatrix, lengths two and one-half inches, from the nasal protuberance to the anterior edge of the raised fragment of the frontal bone, is quite unsightly. Upon the top of the head, and covered with hair, is a large unequal depression and elevation-a quadrangular fragment of bone, which was entirely detached from the frontal and extending low down upon the forehead, being still raised and quite prominent. Behind this is a deep depression, two inches by one and one-half inches wide, beneath which the pulsations of the brain can be perceived. Partial paralysis of the left side of face. His physical health is good, and I am inclined to say that he has recovered.

Harlow’s remarks suggest that Gage’s overall appearance was generally unremarkable, the exception being the ptosis of his left eyelid which can clearly be seen in the daguerreotype discovered in 2009. Harlow also documented apparent changes in Gage’s personality:

Has no pain in the head, but says it has a queer feeling which he is not able to describe. Applied for his situation as foreman, but is undecided whether to work or travel. His contractors, who regarded him as the most efficient and capable foreman in their employ previous to his injury, considered the change in his mind so marked that they could not give him place again. The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual passions of a strong man. Previous to his injury, though untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart business man, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage.’ (Harlow, 1868 , pp. 338–340)

After Harlow published his initial report in December 1848, he was contacted by Dr. Henry Bigelow, a prominent Boston surgeon and Harvard professor. Bigelow ( 1850 ) acknowledged having been verbally informed of the accident but was highly skeptical as to the facts of the case. Using Harlow as an intermediary, he provided funds for Gage to travel to Boston for an examination. Given Harlow’s determination that his patient was now “quite well” (p. 330), Gage accepted Bigelow’s offer.

Dr. Henry Bigelow: A Second Opinion

Henry Bigelow, M.D. is perhaps one of the most interesting individuals with whom Gage interacted. Bigelow was a prominent surgeon at Massachusetts General Hospital and a professor of surgery at Harvard University who was instrumental in bringing Gage’s accident to medical prominence. To fully appreciate how his involvement was necessary in validating Gage’s injuries and treatment to the skeptical medical community at that time, one must understand Bigelow’s social background and medical training that allowed him to lend gravitas to Harlow’s report (Schatzki, 1994 ).

Bigelow was the eldest son of an affluent Massachusetts family whose father was a renowned surgeon and Harvard Medical School professor who was socially well connected in Boston society. He entered Harvard at age 15 intent on following his father’s medical career. His memoirs suggest an egotistical individual, self-described as having “personal magnetism,” being a “brilliant operator,” and to those who observed his surgical technique “was to recognize a master” (Bigelow, 1894 , pp. 37–38).

In spite of these self-described laudable attributes, Bigelow’s actual behavior was in many circumstances otherwise. While at Harvard, he was reprimanded for noise violations after disturbing the college with a trumpet he made from a tin coffee pot. He also made nitrous oxide for the Rumford student chemistry club and compromised his health from multiple binges. Perhaps as an early indication of his fascination with anesthesia, he rationalized his abuse of the inhalant as being one of his “most important investigations.” While these pranks were tolerated by Harvard’s administration, he was eventually expelled in 1834 along with five freshmen and the entire sophomore class for taking part in a three-month student rebellion. Although he dismissed damages from the uprising by describing it as a “stirring incident,” the revolt included burning a classroom, exploding a device in Holden Chapel, assaulting two watchmen, and using gunpowder to burn the Harvard’s president, Quincy, in effigy (McCaughey, 1970 ). Compounding the group’s vandalism, Bigelow was personally sanctioned for having three muskets in his dorm room at Hollis Hall that he discharged multiple times into a wooden post (pp. 10–12) and for nearly wounding a fellow student named James Elliot Cabot “by the accidental discharge of a gun” (Bigelow, 1894 , pp. 9–13).

After his expulsion he studied anatomy and physiology at Dartmouth College with Oliver Wendell Holmes, visited Cuba for a period of months to remedy his respiratory difficulties (allegedly from his nitrous abuse), spent time in Italy, Egypt, Paris, and London, where he studied with Longet and reportedly “mastered” auscultation with the stethoscope under Sir James Paget. He finally returned to the Boston, where he eventually he received his medical degree from Harvard in 1841 (Bigelow, 1894 pp. 24–25).

Historically Bigelow is best known for being the first physician to publish on the surgical application of ether, having first watched Morton and Warren demonstrate its use with two cases. in October 1846 (Morton & Woodbury, 1895 ). He used the inhalant on one of his own cases a month later and published his account, thereby circumventing publication by the actual pioneers of the discovery. In doing so was given credit for establishing its medical importance, which contributed to his surgical appointment that same year at Massachusetts General Hospital. Interestingly, he also addressed the anesthetic properties of kerosene after experimenting with self-inhalation of its vapor (Bigelow, 1846 , 1894 ).

Having established his medical credentials, it is not surprising that Bigelow was highly skeptical of the occurrence of Gage’s accident and his survival. The injury as described with the limited loss of function was so inconceivable that many in the medical community were highly doubtful and thought that the facts were misunderstood. In Bigelow’s published remarks, he noted that “A physician who holds in his hand a crowbar, three feet and a half long, and more than thirteen pounds in weight, will not readily believe that it has been driven with a crash through the brain of a man who is still able to walk off, talking with composure and equanimity of the hole in his head” (Bigelow, 1850 , p. 19).

In January 1850, Bigelow secured Gage’s presence and exhibited him to Boston’s medical community for a number of weeks during which Gage was subject to multiple examinations that confirmed the case facts as described by Harlow. Having presented him as a case study in medical rounds, Bigelow reported, “I have been able to satisfy myself as well of the occurrence and extent of the injury as of the manner of its infliction” (Bigelow, 1850 , p. 13). Bigelow demonstrated the injury to colleagues by recreating the path of the tamping iron through an anatomical (cadaver) skull and in doing so verified how the bar could enter, pass through, and exit the cranium without inflicting a fatal lesion. As a result, he wrote, “This is the sort of accident which happens in the pantomime at the theatre, but not elsewhere. Yet there is every reason for supposing it in this case literally true. Being at first wholly skeptical, I have been personally convinced; and this has been the experience of many medical gentlemen who, having first heard of the circumstances, have had a subsequent opportunity to examine the evidence” (Bigelow, 1850 , p. 13).

Bigelow’s importance in Gage’s case lies in his establishing a second opinion and, given his position of prominence in Boston medical society and his reputation, to corroborate Harlow’s findings. In addition, his recapitulation of Harlow’s treatment provided an additional source of documentation in a highly-respected medical publication, The American Journal of the Medical Sciences . In doing so, he afforded the case broader public exposure to the medical community of the northeast United States, which other physicians then began to cite (Butler, 1851 ). Of equal importance to Bigelow’s gravitas was his successful obtainment of a collection of affidavits by those who either witnessed the accident or saw Gage afterwards. Through letters to Harlow, he collected critical documents that formally affirmed the facts of the case, and included these accounts in his 1850 publication. By doing so, he resolved the doubts or reservations held by his medical colleagues who subsequently supported his opinion. “This is no fancy picture drawn to task credulity, but a well authenticated fact” (Butler, 1851 , p. 99).

Gage’s Change in Mental Status: Frontal Cortical Injury

Gage is often cited as an example of a frontal cortical injury with subsequent changes in personality or comportment (Mesulam, 1985 ; Prigatano, 1992 ; Suchy, 2016 ). It has been suggested that there are three principal frontal-subcortical circuits involved in cognitive, emotional, and behavioral processes: dorsolateral, ventromedial, and orbitofrontal, each corresponding to areas of the prefrontal cerebral cortex.

The dorsolateral frontal cortex mainly projects to the dorsolateral head of the caudate nucleus and has been linked to executive functions, such as those measured on tests of mental flexibility, planning, abstraction, and deductive reasoning. It was this link between dorsolateral structures and executive reasoning that led to early conclusions that the frontal lobes were the seat of executive reasoning, so much so that such tasks were described as tests of “frontal lobe functioning.”

The ventromedial circuit projects from the anterior cingulate gyrus to the nucleus accumbens in the basal forebrain. Ventromedial lesions are associated with apathy, amotivational states, social withdrawal, reduced initiation, and motor slowing (Herman, et al., 1992 ; Herman & Cullinan, 1997 ).

It has been proposed that the anterior cingulate cortex (ACC) can be further sectioned into anatomically and functionally distinct subdivisions, based upon its connections to other frontal lobe regions, notably a supracallosal region of the ACC. This area projects to dorsolateral frontal areas and subcallosal portions of the ACC, which then connect to the posterior orbitofrontal regions. While supracallosal ACC lesions are associated with executive impairment and related cognitive inefficiencies, subcallosal ACC lesions are associated with control of respiration, blood pressure, and other autonomic functions (Herman & Cullinan, 1997 ).

The orbitofrontal cortex projects to the ventromedial caudate nucleus and is linked to socially inappropriate behaviors, such as disinhibition, impulsivity, and anti-social behaviors, behavioral inconsistency, and unreliability (Cullinan, et al., 1995 ). These are the behaviors described by Harlow ( 1868 ) in the aftermath of Gage’s injury.

Advances in neuroimaging and modeling technology have led to refined hypotheses as to the likely path of the tamping iron that produced Gage’s brain injury. Based upon magnetic resonance imaging (MRI) data and three dimensional modeling, Damasio and associates (1994) concluded that Gage’s brain lesion involved the anterior half of the left orbital-frontal context, the polar and anterior mesial frontal cortices, and the anterior-most portions of the anterior cingulate gyrus. That is, his lesion affected the ventromedial region of both frontal lobes while sparing the dorsolateral regions. They further concluded that “Gage … fits a neuroanatomical pattern we have identified within a group of individuals with frontal damage. Their ability to make rational decisions in personal and social matters is invariably compromised and so is their processing of emotion.”

More recently, Van Horn and associates (2012) employed diffusion weighted imagery (DWI) and MRI modeling and determined that considerable cortical and subcortical damage to white matter tracts was localized to the left frontal lobe. In their modeling, it was estimated that the tamping iron damaged approximately 11% of the white matter in the frontal lobe and approximately 4% of the cerebral cortex. They hypothesized that damage occurred to the superior longitudinal fasciculus, which connects all lobes in both hemispheres, and the uncinated fasciculus, which links the limbic system to parts of the frontal lobe. As such, some brain structures affected were quite remote from the site of impact, but nonetheless contributed to Gage’s changes in behavior and comportment in the aftermath of his brain injury.

According to Bigelow ( 1850 ), these mental status changes were fairly marked. He described Gage as “fitful” and “irreverent”; he demonstrates “but little deference for his fellows” (a far cry from the Gage who was a “great favorite” of his men) and is “at times pertinaciously obstinate, yet capricious and vacillating”; he employs “the grossest profanity,” which was not typical pre-injury. Harlow also seems to imply that Gage had an unwillingness to carry out his plans, writing that they were “no sooner arranged than they are abandoned in turn for others appearing more feasible” (p. 340). This characterization seems to contrast sharply with Harlow’s descriptions of Gage’s pre-injury mental status, when he was “persistent in executing all his plans of operation” (p. 340) and possessed “an iron will” (p. 330). The Rutland and Burlington railroad company, who previously employed Gage and regarded him as highly capable and dependable, now “considered the change in his mind so marked that they could not give him his place again” (p. 339).

Long-Term Recovery

Harlow ( 1868 ) provided an account of Gage’s long-term recovery, as relayed by Gage’s mother. According to Harlow, sometime after his examination in 1850, Gage traveled throughout New England, including to Boston and New York. While in New York, that Gage spent some time “at Barnum’s,” apparently in reference to P. T. Barnum’s famous New York museum (Bigelow, 1894 , pp. 119–123).

Barnum’s autobiography (Barnum, 1855 ) contains no mention of Gage (an observation also noted by Macmillan, 2000a ), and a review of the Barnum’s Museum Illustrated Guide from 1850 similarly does not mention him (The Lost Museum Archive, n.d.) ; however, there is also some evidence to support Harlow’s assertion that Gage participated in public exhibition. Macmillan and Lena ( 2010 ) describe first a letter by Henry Bigelow which also states that Gage appeared at Barnum’s museum. Second, they describe two advertisements for appearances by Gage, one for an appearance in Concord, New Hampshire, and another for Montpelier, Vermont. While it is unclear if Gage’s stay at Barnum’s was extended or quite brief, he clearly seems to have appeared at the museum for a time and also participated in other public appearances, possibly independent of the museum and possibly under his own management (Macmillan & Lena, 2010 ).

Harlow reports that Gage took a job in the livery stable of Jonathan Currier in 1851, apparently abandoning exhibition due to lack of public interest (Macmillan & Lena, 2010 ). After working in Currier’s stable for “nearly a year and a half” (Harlow, 1868 , p. 340), Gage travelled to Valparaiso, Chile, with an acquaintance who planned to establish a horse drawn coach business to transport passengers from the coastal region to Santiago.

At this point there is evidence that the dates in Harlow’s report become somewhat less accurate; for example, while he ends by stating that Gage died in 1861, records list his burial date as May 23, 1860, making Harlow’s history inaccurate by a year in this regard. Gage likely remained in Chili until 1859, at which time he travelled to San Francisco, home to his mother and sister, reportedly due to failing health. Gage briefly worked on a farm in Santa Clara although “did not remain there long,” and approximately three months before his death suffered seizures, described as “a fit,” followed by “two or three fits in succession” (p. 341). He then suffered a “severe convulsion” the day before his death, followed by repeated convulsions until his time of death at approximately 10 p.m. the following day.

Gage’s Final Resting Place

Gage was first interred at Lone Mountain Cemetery (renamed Laurel Hill in 1864) on May 23, 1860; however, he would not finally lie undisturbed until nearly eight decades later. Gage’s body was exhumed in 1867 at the request of John Harlow. Because no autopsy of Gage was performed upon his death, Harlow requested that Gage’s mother give him possession of the skull and tamping iron for the benefit of the historical record (Harlow, 1868 ). The skull and tamping iron were retrieved and sent to Harlow, who subsequently donated them to the Museum of the Medical Department of Harvard University (now the Warren Anatomical Museum), where they are still on display in the Countway Library of Medicine. The remainder of Gage’s body was reinterred and would remain at Laurel Hill. But unstoppable urban progress prompted San Francisco supervisors to prohibit new burials in the city and eventually declare the city’s old cemeteries a public nuisance. Heated debate over what do with the cemeteries’ tens of thousands of occupants, as well as the many ornate and expensive monuments, prevented any action from being taken for a number of years. By the early 1900s Laurel Hill was in a lamentable state of disrepair:

At Laurel Hill Cemetery high weeds obstructed the once stylish paths and avenues. Statues were overturned and carried off. Scavengers methodically pillaged vaults. Coffins were hacked open and bones strewn about. Entire skeletons were stolen (Svanevik & Burgett, 1992 , p. 28).

Fortunately, Gage was not among the many dead who had their final resting place desecrated by vandals. In 1937 the city of San Francisco ordered the transfer of remains from Laurel Hill to Cypress Lawn in Colma, California (Svanevik & Burgett, 1992 ). Gage’s transfer slip (Figure 41.6 ) indicates his remains were transferred from Laurel Hill on May 17, 1940, and interned in vault 962 of the Pioneer Monument, located in Cypress Lawn Memorial Park (H. Lopez, personal communication, May 21, 1996).

Why Study Gage?

What contemporary significance does the case study of Gage’s injury hold for neuropsychology? The detailed descriptions of his injury and meticulous notes recording his changes in physical and cognitive status during and after recovery lend the case a uniqueness that is unparalleled by most medical case studies of the period. In this sense, Gage’s case provides at least four compelling reasons for ongoing study by clinicians interested in brain-behavior relationships. First, it is of historical importance to neuropsychology. Second, it remains clinically relevant to students, psychologists, physicians, and scientists in the fields of neuroscience, physical medicine, and rehabilitation, particularly for those interested in brain injuries, localization, and the frontal lobes (Macmillan, 1994 ). In addition, most reiterations in texts and scholarly articles contain errors, and lastly, the mechanism of injury and accompanying historical facts continue to maintain a high level of interest that is referenced by multiple medical and scientific disciplines.

Gage’s transfer slip

Historical Importance

The historical importance of Gage’s case can be found in the influence it had on 19th century thinking about the brain and behavior. It was one of the first in a series of single-case medical studies published in the 1800s and early 1900s that provided a foundation for understanding the brain’s function and mental status changes following disease, insult, or injury to the central nervous system.

Following publication of Gage’s injury, Paul Broca ( 1861 ) published his famous case of the patient Leborgne, known as “Tan,” who experienced language deficits associated with a left frontal lesion as the result of syphilis (Lazar & Mohr, 2011 ). In 1880 Josef Breuer presented Bertha Pappenheim, “Anna O.,” to the medical community as an example of psychogenic paralysis of vision and speech, hence an early example of conversion disorder (Breuer & Freud, 2000 ). Sigmund Freud ( 1909 ) published his famous case of severe anxiety of horses of Herbert Graf or “Little Hans,” titled “Analysis of a Phobia in a Five-year-old Boy.” Lastly, in the 1920s Alexander Luria presented his synesthesia case of the journalist Solomon Shereshevsky to describe how stimulation of one sensory pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway (Luria, 1966 ).

Clinical Relevance

Gage’s injury is significant to neuroscience and neuropsychology, in particular, because his attending doctor, John Harlow, conducted the first detailed documentation of frontal cortical damage altering emotional regulation and behavior. Not surprisingly, many who learned of the accident doubted the mechanism of injury, assuming that survival from a traumatic impalement of the brain of this magnitude was inconceivable. Even the Reverend Joseph Freeman, who saw Gage immediately after the accident, responded with disbelief upon being told that the tamping iron passed through his head, simply stating “That is impossible” (Bigelow, 1850 , p. 15).

Though many are commonly met with skepticism or disbelief, there are a number of historical references to the treatment of traumatic brain injuries (Chaucer, 2005 , p. 770; Cronyn, 1871 ; Karger, 2001 ; Leny, 1793 ). Most describe military surgical interventions following impalement by projectiles such as spears, javelins, lances, and arrows (Bollet, 2002 ). One of the oldest examples is the ancient Egyptian medical text known as the Edwin Smith Papyrus (1600 bce ), which categorized trauma by organ, including brain injuries classified by scalp lacerations, penetration of the skull, and injury to the brain (Nunn, 1996 ; Reitan & Wolfson, 2000 ; Wilkins, 1992 ).

It is understandable that a lack of knowledge about brain functioning led to a simplistic approach to the treatment of brain trauma. For example, in his medical writings Hippocrates addressed head injuries by focusing on consequences of insults to the skull (Wilkins, 1972 ), whereas Galen concentrated on the ventricles and their association with psychic pneuma and the rational soul to explain changes in consciousness (Finger, 1994 ). Ganz ( 2013 ) writes that this approach continued until the 1700s, when French, English, Irish, and Scottish surgeons began to more accurately identify alterations in mental status subsequent to traumatic brain injury to the cerebral cortex. Specifically, he identifies Henri-Francois Le Dran, Percival Pott, James Hill, Sylvester O’Halloran, William Dease, and John Abernethy as being seminal figures in the development of surgical interventions of the brain.

One of the most famous historical examples similar to Gage’s injury is that of Henry V who, as a prince, was wounded in 1403 on the battlefield in Cheshire, England. After a massive barrage of arrows was launched, the future king was struck in the face by an arrow that entered below his eye and to the left side of his nose, penetrating six inches into his skull (Strickland & Hardy, 2011 ). He survived the injury and was treated at Kenilworth castle by John Bradmore, who described in detail his removal of the arrowhead with a mechanical extraction device and the use of resin, wax, herbs, and honey, which served as crude antiseptics, noted to be “good for chilled nerves and sinews” (Cole & Lang, 2003 , p. 97).

Even in the 1800s Gage’s case was not the first to document personality change as a result of frontal lobe injury. Benson and Blumer ( 1975 ) report on a 16-year-old male who suffered a self-inflicted gunshot wound with a black powder pistol which extensively damaged the medial-orbital frontal lobe (de Nobele, 1835 ). Prior to the injury, the adolescent was said to exhibit withdrawn, depressed behavior. Post-injury, his personality seemed markedly changed; he was described as being “happy, vivacious, and jocular” (Stuss & Benson, 1984 , p. 19), despite suffering blindness as a result of the injury. As exemplified here, while Gage’s injury may be the most widely known, frontal lobe injuries due to war, riding or draft animals, hunting, farming, and work accidents were documented long before Gage (Harris, 1847 ; Heustis, 1829 ; Leny, 1793 ) and after his injury (Bird, 1865 ; Cronyn, 1871 ; Fitch, 1852 ; Folsom, 1868 ; Noyes, 1882 ).

Gage’s case however, is unique from other historical examples of traumatic brain injury because of its contribution to our understanding of the role of the frontal lobes. Previously, it had been thought that the frontal lobes had little influence on behavior and cognition, until the absence of executive functioning became apparent following their impairment (Suchy, 2016 ). David Ferrier cited Gage as a primary example of how a frontal lobe injury can alter personality without sensory or motor findings (Neylan, 1999 ) and used Gage’s injury to explain inhibitory and attentional changes in primates and humans. He associated attention with higher cortical functioning and described “its relation to the anatomical substrata of the prefrontal lobes” (Ferrier, 1878 , p. 447). Although he later changed his position, in his first edition of The Functions of the Brain , Ferrier ( 1876 ) proposed a frontal-inhibitory-motor function of the brain and also advocated for cerebral localization using Harlow’s clinical observations to support focal mapping of cerebral functions (Ferrier, 1878 ). Damasio, Grabowski, Frank, Galaburda, and Damasio ( 1994 ) stated that Gage’s case perhaps should have signaled the beginning of the study of the biological basis of behavior, placing Harlow’s observations on par with those of Broca and Wernicke. It is no wonder that most students of neuroscience, medicine, and psychology have been taught about Gage’s change in behavior following cortical damage and the subsequent implication for personality change.

Most Reiterations Contain Errors

It is difficult to find a reiteration of Gage’s case in scholarly articles or texts without finding errors. This is particularly evident in introductory psychology textbooks that discuss Gage’s post-accident recovery and mental status changes (Macmillan, 2000b ); Griggs, 2015 ). Was the instrument of destruction a crowbar or tamping iron (Barker, 1995 )? Did the bar pass through his head or did his physician remove it (Maugh, 2009 )? Did he recover his “faculties of body and mind” (Bigelow, 1850 , p. 14) and retain “in a perfect degree his mental powers” such that “at no time during his recovery was his mind seriously affected” (Butler, 1851 , p. 99) or did he in fact not fully recover his mental faculties, as the American Phrenological Journal claimed after the injury (“Remarkable case of injury,” 1851)? Could he only “briefly sustain work as a stable hand” (Lyketsos, Rosenblatt, & Rabins, 2004 , p. 250) or did he maintain consistent employment after his recovery? After the injury was he rational? Did he demonstrate a lack of foresight (Harlow, 1868 ) or was his disfigurement so traumatic that it altered his personality (Kotowicz, 2007 )? Did Gage’s injury inspire the development of 19th century neurosurgical interventions for brain lesions or the frontal lobotomy procedure (Macmillan, 2000a; Starr, 1848)? The point to be made is that even though the original documents are now easily accessible to researchers and a comprehensive analysis of the case exists (Macmillan, 2000a ), even academic researchers continue to perpetuate errors and get the facts of this case wrong.

In his work, An Odd Kind of Fame: Stories of Phineas Gage , Malcolm Macmillan ( 2000a ) presents what is likely to be the most extensive research of Gage’s injury ever written. Macmillan hypothesized that errors or misrepresentations present in summaries of Gage’s injury, recovery, and subsequent behavioral changes could be the result of later authors’ ignoring some or all of Harlow’s description of Gage’s recovery and life post-injury. This is likely to lead to largely accurate descriptions of the basic facts of the case (date, time, and nature of the accident; the physical properties of the tamping iron; etc.) but vague, incomplete, inaccurate, or exaggerated descriptions of Gage’s behavioral changes and employment—the story becoming less clear as it moves away from its climax. Macmillan suggests that further exaggerations of Gage’s altered behavior may be the result of generalizations or the over-simplification of damage to the frontal lobe from other, similar case studies that may have been projected onto Gage’s history after the fact.

Numerous examples can be found in the literature that inaccurately cite the Gage case to illustrate a particular character trait such as wantonness, virulence, and immorality following damage to this area of the cortex. Inconsistent with Harlow’s behavioral observations, which were also supported by Bigelow’s affidavits collected from eyewitnesses, Biever and Karinch ( 2012 ) describe Gage as having become “sexually promiscuous and hostile” and “totally disinhibited,” and therefore conclude that “Phineas Gage’s limbic brain was apparently destroyed, but his cognitive brain survived intact” (p. 42). To paraphrase what Macmillan has said on a number of occasions (e.g., Kean, 2014 ; Lewandowski, 1998 ; Macmillan, 2000a , p. 333), the initial reports by Harlow and Bigelow come closest to accurately capturing the facts surrounding Gage’s accident, treatment, and recovery, and they should be treated as the primary sources for facts.

Uniqueness and Interest

Lastly, Gage’s injury and his recovery are very interesting. The patient and his attending doctor were very unremarkable people who were brought into the annals of science and history by this one remarkable event (Lewandowski, 2018 ). The mechanism of injury is a source of fascination that has somewhat of a carnival side-show quality. Gage is one of the most frequently cited cases from 19th century medical literature. Harlow himself said in his 1868 publication that Gage was “the man for the case,” that the iron’s smoothness reduced damage to concussion/compression, and that the area of the brain compromised “was the best fitted of any part of the cerebral substance to sustain the injury” (p. 344). As a result, the case of Phineas Gage continues to lend great interest and contemporary relevance to neuroscientists across a broad range of psychological and medical specialties.

Phineas Gage’s improbable survival from the blast that caused a tamping iron to pass through his head occurred during a time when survival from catastrophic brain injury was quite rare. The unique circumstances of the case—including the advantageous size, shape, and texture of Gage’s tamping iron, the limited concussive/compressive damage secondary to the force of impact, and the sequence of techniques employed by Harlow during Gage’s acute treatment—contributed to his survival and the implications of the case for the medical science of the time. Moreover, it occurred at a time when the particular functions associated with the cerebral cortex were for the most part unknown and thought to be unknowable. Because those very few individuals who suffered penetrating brain injuries and sustained pre-frontal trauma survived, it was assumed that these portions of the brain were behaviorally silent.

The Gage case was the first to extensively document that changes in such complex and seemingly inherent qualities such as judgment, impulse control, demeanor, and temperament were not only associated with the brain, but with particular regions within it. It challenged the medical community to begin to question if temperament could be subject to external influences and therefore amenable to scientific principles such as modification, prediction, and clinical treatment.

Gage’s injury occurred at a time when surgical advances and the treatment of infection had progressed to the point where at least some severely traumatically injured patients could survive long enough to be clinically observed and where individuals so injured would be triaged in a manner that would permit them access to heroic care. This would not have occurred if mediums for the exchange of medical information had not reached a tipping point, such that case reports, procedures, and findings previously occurring in isolation could be posted, compared, and aggregated in recently established medical journals. Consider also that while Harlow did not have the resources of hospitals, medical schools, medical meetings, and apothecaries that his physician colleagues had in urban areas, he was prepared through clinical training by a group of renowned medical professors for this very complex traumatic brain injury that even he equated with a military injury.

Gage is among the first well-documented cases of brain-injury where the roles of the patient and the treating physician evolved into intertwined and extended friendships or stewardships, such that long-term follow-up was possible and the changing nature of brain injuries over time could be detailed and explicated. There are echoes of the relationship between Gage and Harlow in the cases of “S.” (Luria), “Tan” (Broca), and Lelong (Wernicke), through to that between Corkin and the amnest, “H.M.” Gage was the first case of which we are aware that offered rich and compelling descriptions of the effects of brain injury over time. In fact, the copious notes taken by Harlow immediately after the accident and throughout Gage’s treatment and recovery have largely (but not completely) precluded the case from accusations of exaggeration and frank invention that haunt mid-19th century medical scholarship.

This, then, may be the reason that the case of Phineas Gage continues to have an enduring influence on contemporary neuropsychology. Many of us were first drawn to neuropsychology because of our interest in the human consequences of brain injuries, in the ways in which the complex activities of normal people could be dramatically damaged by injuries to their brains, and the ways in which that knowledge could be used to help them adapt or recover. This may be the lasting legacy of the case of Phineas Gage: the degree to which the facts and mythology of this case have captured the imagination of generations of future neuropsychologists.

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Lessons of the brain: The Phineas Gage story

Harvard Correspondent

In 1848, an iron bar pierced his brain, his case providing new insights on both trauma and recovery

Imagine the modern-day reaction to a news story about a man surviving a three-foot, 7-inch, 13½-pound iron bar being blown through his skull — taking a chunk of his brain with it.

Then imagine that this happened in 1848, long before modern medicine and neuroscience. That was the case of Phineas Gage.

Whether the Vermont construction foreman, who was laying railroad track and using explosives at the time of the industrial accident, was lucky or unlucky is a judgment that Warren Anatomical Museum curator Dominic Hall puzzles over to this day.

“It is an impossible question, because he was extraordinarily unlucky to have an iron bar borne through his skull, but equally lucky to have survived, on such a low level of care,” said Hall. “We are lucky, to have him.”

Gage’s skull, along with the tamping iron that bore through it, are two of the approximately 15,000 artifacts and case objects conserved at the Warren, which is a part of the Center for the History of Medicine in Harvard’s Francis A. Countway Library of Medicine .

The resultant change in Gage’s personality — when he went from being well-liked and professionally successful to being “fitful, irreverent, and grossly profane, showing little deference for his fellows” and unable to keep his job — is widely cited in modern psychology as the textbook case for post-traumatic social disinhibition.

But as the years have gone by and we’ve learned more about his life, argued Hall, the teachings have changed.

“In 1848, he was seen as a triumph of human survival. Then, he becomes the textbook case for post-traumatic personality change. Recently, people interpret him as having found a form of independence and social recovery, which he didn’t get credit for 15 years ago.”

When Gage died 12 years after the accident, following epileptic seizures, his body was exhumed, while his skull and tamping iron were sent to the physician who had cared for him since the accident, John Harlow. Harlow later donated the items to the Warren, where they have remained for 160 years.

“In many ways, I see Gage similarly to how you would see a portrait of one of the famous professors hanging on the wall — he’s an important part of Harvard Medical School’s identity,” said Hall. “By continually reflecting on his case, it allows us to change how we reflect on the human brain and how we interact with our historical understanding of neuroscience.”

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The Curious Case of Phineas Gage

First Online: 03 January 2022

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Laura McHale 2

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This chapter examines the brain injury (in 1848) of Phineas Gage, one of the most famous cases in neuroscience. We explore the role of emotional processing in decision-making. We challenge the Cartesian framework, so dominant in leadership, management, and organizational communication. Lastly, we explore the somatic marker hypothesis and how it is important for understanding less visible aspects of work.

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McHale, L. (2022). The Curious Case of Phineas Gage. In: Neuroscience for Organizational Communication. Palgrave Macmillan, Singapore. https://doi.org/10.1007/978-981-16-7037-4_3

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Mapping Connectivity Damage in the Case of Phineas Gage

John darrell van horn.

1 Laboratory of Neuro Imaging (LONI), Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America

Andrei Irimia

Carinna m. torgerson, micah c. chambers, ron kikinis.

2 Surgical Planning Laboratory, Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

Arthur W. Toga

Conceived and designed the experiments: JVH AWT RK. Performed the experiments: MCC CMT AI. Analyzed the data: MCC AI CMT. Contributed reagents/materials/analysis tools: AWT RK. Wrote the paper: JVH AI MCC. Provided computational resources and database access needed for neuroimaging data analysis: AWT. Provided access to data essential for the study: RK.

Associated Data

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a “tamping iron” was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25–36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized “average” brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient.

Introduction

The mapping of human brain connectivity through the use of modern neuroimaging methods has enjoyed considerable interest, examination, and application in recent years [1] , [2] . Through the use of diffusion weighted (DWI) and magnetic resonance imaging (MRI), it is possible to systematically assess white matter (WM) fiber pathways between brain regions to measure fiber bundle properties, their influence on behavior and cognition, as well as the results of severe brain damage. The potential for using combined DWI/MRI methods to understand network-level alterations resulting from neurological insult is among their major research and clinical advantages.

In this paper, we investigate the detailed connectomics of a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. Few cases in the history of the medical sciences have been so important, interpreted, and misconstrued, as the case of Phineas P. Gage [3] , in whom a “tamping iron” was accidentally shot through his skull and brain, resulting in profound behavioral changes, and which contributed to his death 151 years ago. On September 13th, 1848, the 25-year old Phineas P. Gage was employed as a railroad construction supervisor near Cavendish, Vermont to blast and remove rock in preparation for the laying of the Rutland and Burlington Railroad. Having drilled a pilot hole into the rock and filling it partially with gunpowder, he instructed an assistant to pour sand into the hole atop the powder. Averting his attention for a moment to speak with his men, he apparently assumed the sand had been added. He then commenced dropping the end of a 110 cm long, 3.2 cm diameter iron rod into the hole in order to “tamp” down its contents. The 13 lb. iron struck the interior wall of the hole causing a spark to ignite the powder which, in turn, launched the pointed iron rod upwards, through the left cheek of Mr. Gage just under the zygomatic arch, passing behind his left eyeball, piercing his cranial vault under the left basal forebrain, passing through his brain, and then exiting the top and front of his skull near the sagittal suture. A large amount of brain tissue was expelled from the opening and the rod was found later “smeared with blood and brains”, washed in a stream, and, eventually, returned to him. After receiving treatment and care from Dr. John Martyn Harlow over subsequent weeks, Mr. Gage was able to recover sufficiently from his physical injuries and return to his family in nearby New Hampshire. However, reports of profound personality changes indicate that he was unable to return to his previous job and caused co-workers to comment that he was “no longer Gage.” Following several years of taking manual labor jobs and travelling throughout New England and eventually to Valparaiso, Chile, always in the company of “his iron”, he was reunited with his family in San Francisco whereupon Mr. Gage died on May 21, 1860, nearly 12 years after his injury – presumably due to the onset of seizures evidently originating from damage resulting from the tamping rod incident. Several years later, Dr. Harlow, upon learning of Gage's death, asked Gage's sister's family to exhume his body to retrieve his skull and rod for presentation to the Massachusetts Historical Society and deposition with Harvard Medical School where, to this day, it remains on display in the Warren Anatomical Museum in the Francis A. Countway Library of Medicine at Harvard Medical School ( Fig. 1a ).

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a) The skull of Phineas Gage on display at the Warren Anatomical Museum at Harvard Medical School. b) CT image volumes were reconstructed, spatially aligned, and manual segmentation of the individual pieces of bone dislodged by the tamping iron (rod), top of the cranium, and mandible was performed. Surface meshes for each individual element of the skull were created. Based upon observations from previous examinations of the skull as well as upon the dimensions of the iron itself, fiducial constraint landmarks were digitally imposed and a set of possible rod trajectories were cast through the skull. This figure shows the set of possible rod trajectory centroids which satisfied each of the anatomical constraints. The trajectory nearest the mean trajectory was considered the true path of the rod and was used in all subsequent calculations. Additionally, voxels comprising the interior boundary and volume of the cranial vault were manually extracted and saved as a digital endocast of Mr. Gage's brain cavity. c) A rendering of the Gage skull with the best fit rod trajectory and example fiber pathways in the left hemisphere intersected by the rod. Graph theoretical metrics for assessing brain global network integration, segregation, and efficiency [92] were computed across each subject and averaged to measure the changes to topological, geometrical, and wiring cost properties. d) A view of the interior of the Gage skull showing the extent of fiber pathways intersected by the tamping iron in a sample subject ( i.e. one having minimal spatial deformation to the Gage skull). The intersection and density of WM fibers between all possible pairs of GM parcellations was recorded, as was average fiber length and average fractional anisotropy (FA) integrated over each fiber.

The amount of damage to Mr. Gage's left frontal cortical grey matter (GM) with secondary damage to surrounding GM has been considered by several authors with reference to Gage's reported change in temperament, character, etc [4] , [5] , [6] ( Table 1 ). With the aid of medical imaging technology, two previous published articles have sought to illustrate the impact of the rod on Mr. Gage's skull and brain. Most famously, Damasio et al. [7] illustrated that the putative extent of damage to the left frontal cortex would be commensurate with the disinhibition, failures to plan, memory deficiencies, and other symptoms noted in patients having frontal lobe injury. Ratiu et al. [8] sought to illustrate the trajectory of the tamping iron, characterize the pattern of skull damage, and explain potential brain damage using a single, example subject. However, while many authors have focused on the gross damage done by the iron to Gage's frontal cortical GM, little consideration has been given to the degree of damage to and destruction of major connections between discretely affected regions and the rest of his brain.

Examiner	Destroyed	Damaged
Harlow, 1848	Left frontal	Not stated
Phelps, 1849	Not stated	Not stated
Bigelow, 1850	Central left frontal, front of left temporal	Left ventricle, medial right frontal
Harlow, 1868	Left frontal only	Left lateral ventricle, part of left temporal
Dupuy, 1873	“absolue” left frontal	Not stated
Dupuy, 1877	Broca's area, Sylvian artery, Island of Reil	Not stated
Ferrier, 1877	Left frontal only	Not stated
Ferrier, 1878	Left prefrontal	Tip of left temporal
Hammond, 1871	Left anterior only, 3 frontal convolution and Island of Reil escaped	Not stated
Cobb, 1940, 1943	Large part of left and some right prefrontal	Large parts of left and some right prefrontal
Tyler and Tyler, 1982	Left anterior frontal, tip of left temporal, anterior horn of left lateral ventricle, head of caudate nucleus and putamen, right hemisphere – including right superior and cingulated gyri
H. Damasio et al., 1994	Anterior half of left orbital frontal cortex, polar and anterior mesial frontal cortices, anterior-most part of anterior cingulated gyrus, right hemisphere similar but less marked in orbital frontal region	Medial and superior right frontal
Ratiu and Talos 2004	Limited to the left frontal lobe and spared the superior sagittal sinus

WM fasciculi link activity between cortical areas of the brain [9] , [10] , become systematically myelinated through brain maturation [11] , govern fundamental cognitive systems [12] , and may be disrupted in neurological [13] and psychiatric disease [14] . Penetrative TBI in cases of wartime [15] , industrial [16] , gunshot [17] , or domestic [18] injury often result in significant damage to brain connectivity, loss of function, and often death. Yet, in some instances, recovery from objects penetrating WM [19] have been reported with minimal sequelae [20] . Neuroimaging studies of WM tracts in TBI have revealed not only significant acute damage to fiber pathways but also that measures of fiber integrity can show partial fiber recovery over time [21] , presumably due to cortical plasticity [22] in non-penetrative cases.

Given recent interest in the atlasing of the human WM connectome (e.g. http://www.humanconnectomeproject.org ), a detailed consideration of the putative damage to Mr. Gage's connectomics and implications for changes in behavior is provocative and compelling. Nerve damage is superficially evident through reports of eventual loss of sight in Gage's left eye, left eyelid ptosis [23] , and recognition of potential WM damage by other investigators [7] . Further examination of the extent of Gage's WM damage and of its effects on network topology and regional connectedness can offer additional context into putative behavioral changes. Due to the absence of original brain tissue and to the lack of a recorded autopsy from this case, one can only estimate the extent of damage from bony structures and can never be confident concerning which precise brain tissues were impacted. However, brain tissue in situ from a representative population can be considered and it can be assumed that Mr. Gage's anatomy would have been similar. In this examination, we obtained the original high-resolution CT data of the Gage skull used by Ratiu et al. , and computationally estimated the best-fit rod trajectory through the skull. Via multimodal analysis of T1-weighted anatomical MRI and DWI in N = 110 normal, right-handed males, aged 25–36, we quantify the extent of acute regional cortical loss and examine in detail the expected degree of damage to Mr. Gage's WM pathways.

Computationally projecting a model of the tamping iron through the T1 MRI anatomical volumes warped to the Gage skull geometry ( Table 2 ; Fig. 1b–c ; see also Methods ) in light of previously reported anatomical constraints ( Table 3 ) and healthy brain morphometry and connectivity ( Fig. 2 ), the average percentage of total cortical GM volume intersected was 3.97±0.29% (mean±SD), where the cortical regions most affected by the rod (>25% of their regional volumes) included (mean±SD): the left orbital sulcus (OrS; 90.86±6.97%), the left middle frontal sulcus (MFS; 80.33±10.01), the horizontal ramus of the anterior segment of the lateral sulcus (ALSHorp; 71.03±22.08%), the anterior segment of the circular sulcus of the insula (ACirInS; 61.81±18.14%), the orbital gyrus (OrG; 39.45±6.17%), the lateral orbital sulcus (LOrS; 37.96±20.24%), the superior frontal sulcus (SupFS; 36.29±12.16%), and the orbital part of the inferior frontal gyrus (InfFGOrp; 28.22±19.60%). While extensive damage occurred to left frontal, left temporal polar, and insular cortex, the best fit rod trajectory did not result in the iron crossing the midline as has been suggested by some authors (see Methods ). As a result, no direct damage appeared to occur in right frontal cortices as evident from our representative sample cohort. A complete list of all cortical areas experiencing damage is listed in Table 4 .

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The outermost ring shows the various brain regions arranged by lobe (fr – frontal; ins – insula; lim – limbic; tem – temporal; par – parietal; occ- occipital; nc – non-cortical; bs – brain stem; CeB - cerebellum) and further ordered anterior-to-posterior based upon the centers-of-mass of these regions in the published Destrieux atlas [72] (see also Table 6 for complete region names, abbreviations, and FreeSurfer IDs, and Table 7 for the abbreviation construction scheme). The left half of the connectogram figure represents the left-hemisphere of the brain, whereas the right half represents the right hemisphere with the exception of the brain stem, which occurs at the bottom, 6 o'clock position of the graph. The lobar abbreviation scheme is given in the text. The color map of each region is lobe-specific and maps to the color of each regional parcellation as shown in Fig. S2 . The set of five rings (from the outside inward) reflect average i) regional volume, ii) cortical thickness, iii) surface area, and iv) cortical curvature of each parcellated cortical region. For non-cortical regions, only average regional volume is shown. Finally, the inner-most ring displays the relative degree of connectivity of that region with respect to WM fibers found to emanate from this region, providing a measure of how connected that region is with all other regions in the parcellation scheme. The links represent the computed degrees of connectivity between segmented brain regions. Links shaded in blue represent DTI tractography pathways in the lower third of the distribution of fractional anisotropy, green lines the middle third, and red lines the top third. Circular “color bars” at the bottom of the figure describe the numeric scale for each regional geometric measurement and its associated color on that anatomical metric ring of the connectogram.

	Exterior	Interior	Foramen Magnum	Zygomatic Arch
	189 mm	100 mm	30 mm	125.9 mm
Injury Measures	Bottom	Clockwise from	Outside
External Edges of Anterior Wound Bone	32.5 mm	42.7 mm	42.8 mm	36.2 mm
External Edges of Anterior Wound Hole	35 mm	63.3 mm	45.6 mm	39.2 mm
	Inferior Left	Clockwise from	Outside
From Anterior Wound Corners to Nasion	60 mm	102 mm	83 mm	58.4 mm
From Most Superior Portion of Anterior Crack to Anterior Wound Corners	31.5 mm	58 mm	42 mm	2 mm
From Most Anterior Portion of Superior Crack to Anterior Wound Corners	60 mm	0 mm	42 mm	58 mm
	(External) Left Inferior to Right Superior	(External) Right Inferior to Medial Superior
Diagonal Length of Anterior Wound	65.3 mm	47.2 mm

Harlow	Bigelow: Correspondence of Dr. Williams	Bigelow: During Gage's Life	Damasio	Ratiu and Talos
	Inverted Funnel 2 inches in every direction	Linear Cicatrix of an inch in length occupies the left ramus of the jaw near its angle	Mandible intact	the optic canal was spared and the eyeball and the left optic nerve stayed medially
	Size of the hole about that of the rod, although this may take the funnel (hinging) into account	thickening of tissue about the malar bone	Zygomatic arch was mostly intact but had a chipped area - medial and superior edge (grazed)	as the iron's tapered end penetrated the left cheek, it fractured the maxilla and the sphenoid wings. As it passed through the orbit, the left half of the bony face swung laterally
	Initially missed the facial wound, had to be pointed out by Gage	left eye considerably more prominent, incapable of outward/upward motion, but other motions unimpaired	Last superior molar socket intact, but tooth missing	Anterior to the cingulate gyrus and to the left ventricle.
	Slit from the angle of the jaw forward 1.5 inch, very stretched laterally, and appeared discolored by powder and rust	Irregular and deep sulcus several inches in length, beneath which the pulsations of the brain can be perceived	No closer than 1.5 cm from the mid thickness of the zygomatic arch	SSS not ruptured: “No rhinoliquorhea or other indication for post-traumatic CSF fistula was reported”
			1 cm from the last superior molar	Point out crack in zygomatic bone, however this looks to be in the same spot as the natural suture between the zygomatic and the maxilla
			0.5 cm from the coronoid process of the mandible	actual bone loss at the iron's point of entry into the skull as well as in the iron's path through the orbit and the sphenoid is approximately 50% smaller than the max- imum diameter of the iron. Since the edges of the region of bone loss show little evidence of healing—mostly a few small osteophytes with no considerable callus for- mation, it follows that portions of the skull lateral to the iron must have fractured an hinged open as the iron passed through, and were then drawn back into place elas- tically and spontaneously realigned by the soft tissue
			Could not have hit anterior horn of lateral ventricle	healed fracture line that runs downward from the inferior orbital rim through the inferior orbital foramen, to the alveolar crest above the second molar (fr)
				because the trajectory of the iron went from the left cheek to the midline of the frontal bone above the orbit, the iron must have passed solely through the fronto-orbital and prefrontal cortex in the left hemisphere


	90.8642	6.9738
MFS	80.3275	10.0096
ALSHorp	71.0288	22.0750
ACirIns	61.8052	18.1382
OrG	39.4491	6.1727
LOrs	37.9640	20.2393
SupFS	36.2909	12.1636
InfFGOrp	28.2180	19.6026
InfES	24.3090	10.3200
ACgG/S	23.2818	8.5984
MFG	21.0579	5.5363
SupFG	16.7034	4.2277
TPro	15.9092	13.7996
SupCirIns	13.1850	5.1297
FMarG/S	10.8534	8.1461
MedOrS	7.8242	8.09648
ShoInG	6.5450	6.2824
ALSVerp	5.7157	10.6281
PoPl	5.4607	8.6884
SbOrs	3.6767	6.1917
InfFGTrip	3.4548	4.3119
SupTGLp	2.5458	3.8131
TrFPoG/S	1.7822	6.0115
Left-Can	0.9526	1.2567
MACgG/S	0.8396	2.2467
RG	0.5484	2.0909
PerCaS	0.1570	0.8941
InfFGOpp	0.1303	0.5813
MTG	0.0932	0.5224
Left-Pu	0.0513	0.2833
InfCirInS	0.0316	0.2170
InfTG	0.0150	0.1492
SupFG(rh)	0.0043	0.0285
InfTS	0.0034	0.0365
SupTS	0.0007	0.0076
ACgG/S(rh)	0.0002	0.0023

The amount of total WM volume lost due to the tamping iron was 10.72±5.46% (mean±SD). Examination of lesioned connectivity matrices indicated that fiber bundles from nearly the entire extent of the left frontal cortex were impacted by the presence of the tamping iron (e.g. Fig. 1d ), which in turn affected most of that hemisphere as well as contralateral regions ( Fig. 3 ). The effect of this lesion on network properties was assessed 1) with respect to the healthy intact network, generally, as well as 2) in contrast to the average effects of similarly-sized lesions simulated elsewhere in the cortex, as related to local GM loss as well as distributed loss of connectivity ( Fig. 4a–c ). Metrics representative of three specific global network attributes were examined: characteristic path length (λ, measuring network integration), mean local efficiency (e, segregation), and small worldness (S) ( Table 5 ).

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The lines in this connectogram graphic represent the connections between brain regions that were lost or damaged by the passage of the tamping iron. Fiber pathway damage extended beyond the left frontal cortex to regions of the left temporal, partial, and occipital cortices as well as to basal ganglia, brain stem, and cerebellum. Inter-hemispheric connections of the frontal and limbic lobes as well as basal ganglia were also affected. Connections in grayscale indicate those pathways that were completely lost in the presence of the tamping iron, while those in shades of tan indicate those partially severed. Pathway transparency indicates the relative density of the affected pathway. In contrast to the morphometric measurements depicted in Fig. 2 , the inner four rings of the connectogram here indicate (from the outside inward) the regional network metrics of betweenness centrality, regional eccentricity, local efficiency, clustering coefficient, and the percent of GM loss, respectively, in the presence of the tamping iron, in each instance averaged over the N = 110 subjects.

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WM fiber pathways intersected by the rod were pooled across all N = 110 subjects and examined for a) the relative lengths (w ij ) of affected pathways and b) the relative percentages of lost fiber density (g ij ); c) the bivariate distribution of g ij versus w ij indicating that local fiber pathways were affected, e.g. relatively short pathways proximal to the injury site, as well as damaging dense, longer-range fiber pathways, e.g. innervating regions some distance from the tamping iron injury (see “ Calculation of Pathology Effects upon GM/WM Volumetrics ” for further details).

Network Type	Integration (Characteristic Path Length, )	Segregation (Mean Local Efficiency, )	Small Worldness ( )
	(I) = 7.7222±3.0227 (I) = 5.6377±2.1899 (I)/λ (I) = 1.3697±0.0534	(I) = 0.4824±0.1077 (I) = 0.0805±0.0443 (I)/e (I) = 6.8953±2.1672	= 3.7226±1.0778
	(T) = 7.8893±3.0817 (T)/λ (I) = 1.3987±0.0532	(T) = 0.4607±0.1104 (T)/e (I) = 5.7229±2.0538	= 3.7289±0.9853
	(L) = 8.3826±3.3196 (L)/λ (I) = 1.4869±0.0469	(L) = 0.4352±0.1054 (L)/e (I) = 5.4062±1.5321	= 3.6061±0.7094

Tables 6 and and7 7 provide details on the regional coding used for brain parcellation which were subjected to estimation of the effects of the tamping iron, lesion simulation modeling, and which encode the text on the outer-most rings of Figs. 2 and and3. 3 . Differences in measures of network connectivity due to the rod's passage were apparent in terms of network integration, segregation, but not small worldness as compared to the unlesioned, healthy network. Specifically, when removing those cortical areas and fiber pathways intersected by the iron, characteristic path length was found to be significantly decreased in Gage compared to the intact network ( p ≤0.0001), mean local efficiency was decreased ( p ≤0.0001), while small worldness showed no statistical difference ( p ≤0.9467, ns). Regionally-specific network theoretical metrics in the affected regions and those to which they connect were also affected (see Fig. 5A ). This suggests that, not surprisingly, with significant loss of WM connectivity between left frontal regions and the rest of the brain, the surviving network of brain was likely to have been heavily impaired and its functions considerably compromised.

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A) Cortical maps of regional graph theoretical properties. Regions affected by the passage of the tamping iron include those having relatively high betweenness centrality and clustering coefficients but relatively low mean local efficiency and eccentricity. B) A cortical surface schematic of the relative effects of systematic lesions of similar WM/GM attributes over the cortex for both network integration (i) and segregation (ii). For each mapping, colors represent the Z-score difference between systematic lesions of that area relative the average change in integration taken across all simulated lesions. C) Cortical maps of the differences/similarity between the effects on integration and segregation observed from the tamping iron lesion with that of each simulated lesion. Here black is most similar (e.g. the observed lesion is most similar to itself) whereas white is least similar to (e.g. most different from) the tamping iron's effects on these measures of network architecture.


NEOCORTICAL STRUCTURES
ACgG/S	anterior part of the cingulate gyrus and sulcus	G_and_S_cingul-Ant	255 255 180
ACirInS	anterior segment of the circular sulcus of the insula	S_circular_insula_ant	102 255 255
ALSHorp	horizontal ramus of the anterior segment of the lateral sulcus (or fissure)	Lat_Fis-ant-Horizont	0 255 204
ALSVerp	vertical ramus of the anterior segment of the lateral sulcus (or fissure)	Lat_Fis-ant-Vertical	0 255 255
AngG	angular gyrus	G_pariet_inf-Angular	0 255 0
AOcS	anterior occipital sulcus and preoccipital notch (temporo-occipital incisure)	S_occipital_ant	51 51 255
ATrCoS	anterior transverse collateral sulcus	S_collat_transv_ant	153 0 204
CcS	calcarine sulcus	S_calcarine	102 153 255
CgSMarp	marginal branch (or part) of the cingulate sulcus	S_cingul-Marginalis	255 192 201
CoS/LinS	medial occipito-temporal sulcus (collateral sulcus) and lingual sulcus	S_oc-temp_med_and_Lingual	153 204 255
CS	central sulcus (Rolando's fissure)	S_central	255 51 0
Cun	cuneus (O6)	G_cuneus	0 153 255
FMarG/S	fronto-marginal gyrus (of Wernicke) and sulcus	G_and_S_frontomargin	204 0 51
FuG	lateral occipito-temporal gyrus (fusiform gyrus, O4-T4)	G_oc-temp_lat-fusifor	102 102 255
HG	Heschl's gyrus (anterior transverse temporal gyrus)	G_temp_sup-G_T_transv	102 0 102
InfCirInS	inferior segment of the circular sulcus of the insula	S_circular_insula_inf	0 102 102
InfFGOpp	opercular part of the inferior frontal gyrus	G_front_inf_Opercular	255 204 0
InfFGOrp	orbital part of the inferior frontal gyrus	G_front_inf-Orbital	153 051 0
InfFGTrip	triangular part of the inferior frontal gyrus	G_front_inf-Triangul	255 0 0
InfFS	inferior frontal sulcus	S_front_inf	153 102 0
InfOcG/S	inferior occipital gyrus (O3) and sulcus	G_and_S_occipital_inf	51 153 255
InfPrCS	inferior part of the precentral sulcus	S_precentral-inf-part	255 153 0
IntPS/TrPS	intraparietal sulcus (interparietal sulcus) and transverse parietal sulci	S_intrapariet_and_P_trans	51 255 51
InfTG	inferior temporal gyrus (T3)	G_temporal_inf	255 0 255
InfTS	inferior temporal sulcus	S_temporal_inf	204 0 153
JS	sulcus intermedius primus (of Jensen)	S_interm_prim-Jensen	153 204 0
LinG	lingual gyrus, lingual part of the medial occipito-temporal gyrus (O5)	G_oc-temp_med-Lingual	102 204 255
LOcTS	lateral occipito-temporal sulcus	S_oc-temp_lat	153 153 255
LoInG/CInS	long insular gyrus and central insular sulcus	G_Ins_lg_and_S_cent_ins	0 204 204
LOrS	lateral orbital sulcus	S_orbital_lateral	102 0 0
MACgG/S	middle-anterior part of the cingulate gyrus and sulcus	G_and_S_cingul-Mid-Ant	255 240 191
MedOrS	medial orbital sulcus (olfactory sulcus)	S_orbital_med-olfact	255 102 0
MFG	middle frontal gyrus (F2)	G_front_middle	255 255 051
MFS	middle frontal sulcus	S_front_middle	255 153 51
MOcG	middle occipital gyrus (O2, lateral occipital gyrus)	G_occipital_middle	0 204 244
MOcS/LuS	middle occipital sulcus and lunatus sulcus	S_oc_middle_and_Lunatus	0 51 255
MPosCgG/S	middle-posterior part of the cingulate gyrus and sulcus	G_and_S_cingul-Mid-Post	255 224 203
MTG	middle temporal gyrus (T2)	G_temporal_middle	255 102 204
OcPo	occipital pole	Pole_occipital	0 0 153
OrG	orbital gyri	G_orbital	255 255 153
OrS	orbital sulci (H-shaped sulci)	S_orbital-H_Shaped	255 204 204
PaCL/S	paracentral lobule and sulcus	G_and_S_paracentral	204 255 153
PaHipG	parahippocampal gyrus, parahippocampal part of the medial occipito-temporal gyrus (T5)	G_oc-temp_med-Parahip	204 204 255
PerCaS	pericallosal sulcus (S of corpus callosum)	S_pericallosal	255 164 200
POcS	parieto-occipital sulcus (or fissure)	S_parieto_occipital	204 255 51
PoPl	polar plane of the superior temporal gyrus	G_temp_sup-Plan_polar	204 153 255
PosCG	postcentral gyrus	G_postcentral	204 255 204
PosCS	postcentral sulcus	S_postcentral	153 255 0
PosDCgG	posterior-dorsal part of the cingulate gyrus	G_cingul-Post-dorsal	255 175 201
PosLS	posterior ramus (or segment) of the lateral sulcus (or fissure)	Lat_Fis-post	204 255 255
PosTrCoS	posterior transverse collateral sulcus	S_collat_transv_post	51 102 255
PosVCgG	posterior-ventral part of the cingulate gyrus (isthmus of the cingulate gyrus)	G_cingul-Post-ventral	255 208 202
PrCG	precentral gyrus	G_precentral	204 102 0
PrCun	precuneus (medial part of P1)	G_precuneus	204 255 0
RG	straight gyrus (gyrus rectus)	G_rectus	255 204 153
SbCaG	subcallosal area, subcallosal gyrus	G_subcallosal	255 153 200
SbCG/S	subcentral gyrus (central operculum) and sulci	G_and_S_subcentral	255 102 153
SbOrS	suborbital sulcus (sulcus rostrales, supraorbital sulcus)	S_suborbital	255 51 102
SbPS	subparietal sulcus	S_subparietal	102 153 0
ShoInG	short insular gyri	G_insular_short	51 255 204
SuMarG	supramarginal gyrus	G_pariet_inf-Supramar	204 255 102
SupCirInS	superior segment of the circular sulcus of the insula	S_circular_insula_sup	0 153 153
SupFG	superior frontal gyrus (F1)	G_front_sup	255 102 102
SupFS	superior frontal sulcus	S_front_sup	204 153 0
SupOcG	superior occipital gyrus (O1)	G_occipital_sup	0 0 255
SupPrCS	superior part of the precentral sulcus	S_precentral-sup-part	255 0 102
SupOcS/TrOcS	superior occipital sulcus and transverse occipital sulcus	S_oc_sup_and_transversal	0 102 255
SupPL	superior parietal lobule (lateral part of P1)	G_parietal_sup	153 255 153
SupTGLp	lateral aspect of the superior temporal gyrus	G_temp_sup-Lateral	153 51 255
SupTS	superior temporal sulcus	S_temporal_sup	204 51 255
TPl	temporal plane of the superior temporal gyrus	G_temp_sup-Plan_tempo	153 0 153
TPo	temporal pole	Pole_temporal	255 204 255
TrFPoG/S	transverse frontopolar gyri and sulci	G_and_S_transv_frontopol	255 153 153
TrTS	transverse temporal sulcus	S_temporal_transverse	255 153 255
SUB-CORTICAL STRUCTURES
Amg	Amygdala	Amygdala	159 159 159
CaN	caudate nucleus	Caudate	96 96 96
Hip	hippocampus	Hippocampus	223 223 223
NAcc	nucleus accumbens	Accumbens-area	128 128 128
Pal	Pallidum	Pallidum	64 64 64
Pu	Putamen	Putamen	32 32 32
Tha	Thalamus	Thalamus-Proper	191 191 191
CEREBELLUM AND BRAIN STEM
CeB	cerebellum	Cerebellum-Cortex	255 64 0
BStem	brain stem	Brain-Stem	207 255 48

Abbreviation	Keyword	Abbreviation	Keyword
A	Anterior	Med	Medial
Acc	Accumbens	Mar	Marginal
Ang	Angular	N	Nucleus
B	Brain	Oc	Occipital/occipito-
C	Central	Op	Opercular
Ca	Callosal	Or	Orbital
Cau	Caudate	P	Parietal
Cc	Calcarine	Pa	Para-
Ceb	Cerebellum	Pal	Palladium
Cg	Cingulate	Per	Peri-
Cir	Circular	Pl	Plane
Cla	Claustrum	Po	Pole/polar
Co	Collateral	Pos	Posterior/post-
Cun	Cuneus	Pr	Pre-
D	Dorsal	Pu	Putamen
F	Frontal/fronto-	p	Part
Fu	Fusiform	pl	Plane
G	Gyrus/gyri	R	Rectus
H	Heschl	S	Sulcus/sulci
Hip	Hippocampus/hippocampal	Sb	Sub-
Hor	Horizontal	Sho	Short
In	Insula/insular	Su	Supra-
Inf	Inferior	Sup	Superior
Int	Intra-	T	Temporal
J	Jensen	Tha	Thalamus
L	Lateral/lobule	Tr	Transverse
Lin	Lingual	Tri	Triangular
Lu	Lunate/lunatus	V	Ventral
Lo	Long	ver	Vertical
M	Middle

To further provide a baseline for comparison of the tamping iron lesion against similarly-sized lesions located elsewhere in the cortex, we conducted a systematic random simulation of 500 similarly-sized lesions across our N = 110 healthy subject cohort. The network containing the lesion due to the tamping iron was systematically compared against the distributions of the above mentioned metrics from the simulated lesion set. When paired t -statistics were computed to determine whether tamping iron lesion differed significantly from the standpoint of network metric values, standardized with respect to the intact network, as compared to other brain lesions of the same size, the characteristic path length (integration), mean local efficiency (segregation), and small worldness, while significantly different from that of the intact networks, were not found to be more severe than the average network properties of average similarly sized GM/WM lesion. These results are summarized in Fig. 5B and 5C . These indicate that alterations to network integration resulting from the tamping iron lesion resulted in greater average path length than that of the intact network but which was less than the average effects of other equally sized lesions. Likewise, segregation, as measured using mean local efficiency, was reduced compared to the intact network, but greater than the average effects of the simulated lesions. These results suggest that Mr. Gage's lesion, while severe and certain to have affected WM connectivity in his left cerebral hemisphere and throughout his brain, could have been considerably more severe had the tamping iron pierced other areas of his brain.

The case of Phineas Gage is among the most famous and infamous in the history of brain science. The interpretations of his incredible injury and attempts to characterize it have been ongoing since soon after it occurred. Our consideration sought to provide a modern connectomic understanding of Mr. Gage's injury and put it into context as involving brain WM in addition to the GM damage discussed by other authors. While we, too, are constrained by the relics left from Mr. Gage's life and what evidence can be gleaned from them, work detailed in this article differs considerably from previous examinations of this case and topic in several key areas: we 1) precisely model the trajectory of the tamping iron through high resolution computed tomographic data of Mr. Gage's skull - a rare imaging data set that, until now, had been lost to science for over a decade; 2) geometrically fit N = 110 age, gender, and handedness matched modern subject MRI brain volumes into the Gage cranial vault to assess average cortical metrics and their degree of variability; 3) in so doing, illustrate that while ∼4% of the cortex was intersected by the rod's passage, ∼11% of total white matter was also damaged, and provide estimates of the degree of damage experienced under a well-established brain parcellation scheme; 4) map high angular resolution diffusion neuroimaging tractography into the same space to measure damage to the pair-wise connections between atlas-defined cortical regions; and 5) compare the graph theoretical properties of the observed lesion against those expected from theoretically similar lesions systematically located throughout the brain. In what follows, we comment on our approach and findings.

Trajectory of the Tamping Iron

Various descriptions of the trajectory of the tamping iron through the Mr. Gage's skull have been given, which has understandably led to differing opinions about which parts of his brain were subjected to damage. Harlow, the physician responsible for Gage's initial treatment, documented that only the left hemisphere had been affected while the right remained unaffected [24] . In contrast, Bigelow maintained that some right-sided damage must have occurred. Dupuy [25] agreed with the left sidedness of the trajectory but placed it more posterior, claiming that motor and language areas had been destroyed – supporting the anti-localizationist arguments popular of the era. Ferrier [26] , illustrating that the motor and language areas had been spared, concluded that damage was limited only to the left hemisphere – a conclusion later echoed by Cobb [27] . In their measurements, Damasio et al. estimated the damage to be more frontal and right sided, whereas Ratiu and colleagues concluded that damage was limited to the left frontal lobe and that it did not cross the midline. Central to these differences in interpretation is likely to be how mandible position has been considered. To satisfy the observed anatomical constraints with the mouth closed would result in a greater right-sided inclination of the rod. Yet, as Harlow originally noted, Gage was in the act of speaking to his men at the moment of the injury and, thus, his mouth was likely open. We observe that with the jaw opened, the best-fit rod trajectory satisfying all constraints does not intersect or cross the superior sagittal sulcus and the injury is specific to the left frontal lobe. Thus, our conclusions are congruent with those of Harlow, Ferrier, as well as with those of Ratiu and Talos and, given the detailed computational approach taken, seem to provide the most likely reconstruction of the acute damage caused by the tamping iron.

Alterations of Network Connectivity Due to the Tamping Iron

The loss of ∼11% total WM volume in the left frontal lobe suggests that the iron's effects on Mr. Gage's brain extended well beyond the loss of left frontal GM alone. Overall differences in metrics of network integration as well as segregation were observed relative to intact connectivity, suggesting widespread disruption of networks involving damage to the left frontal and temporal pathways. Alterations indicate major changes to global network topology which affected network-wide efficiency. In the healthy cohort examined here, the region-to-region WM connectedness when in the presence of the rod was found to be associated with several important fiber bundles. Specifically, connectivity was affected between the frontal lobes and the basal ganglia, the insula, limbic, and other major lobes of the left hemisphere, in addition to right frontal, insular, and limbic areas. This severed portions of the uncinate fasciculus (UF) - connecting parts of the limbic system such as the hippocampus and amygdala in the temporal lobe with frontal regions such as the orbito-frontal cortex. The cingulum bundle - the collection of WM fibers projecting from the cingulate gyrus to the entorhinal cortex, allowing for communication between components of the limbic system – was also damaged. Additionally, the superior longitudinal fasciculus (SLF) was impacted – the long bi-directional bundles of neurons connecting the rostral and caudal aspects of the cerebrum in which each association fiber bundle is lateral to the centrum ovale linking the frontal, occipital, parietal, and temporal lobes. Fibers here pass from the frontal lobe through the operculum to the posterior end of the lateral sulcus, where numerous processes radiate into the occipital lobe while others turn downward and forward around the putamen and project to anterior portions of the temporal lobe. The occipito-temporal projection [28] in humans connects the temporal lobe and occipital lobe, running along the lateral walls of the inferior and posterior cornua of the lateral ventricle. The connectivity of the orbital cortex with temporal lobe regions via the UF which is among the last to complete myelination in development [29] , has been shown to be particularly affected in patients with mental illness [30] , and to be related to cognitive deficits in TBI [31] , [32] . WM fascicular damage in these instances was likely an important factor in Gage's reported post-injury symptomatology as well as in his reported and putative behavioral issues.

The obtained results suggest that GM damage had wider reaching influence than previously described and compromised several aspects of Gage's network of WM connectivity. Regions whose connectivity within and between cerebral hemispheres were affected included: the left frontal lobe (the transverse fronto-polar gyrus, fronto-marginal gyrus, middle frontal gyrus, lateral orbital sulcus, orbital sulcus, oribital part of the inferior frontal gyrus, triangular part of the inferior frontal gyrus, inferior frontal sulcus, medial orbital sulcus, orbital gyri, superior frontal gyrus, and opercular part of the inferior frontal gyrus); left insular cortex (horizontal and vertical ramus of the anterior segment of the lateral sulcus/fissure, the anterior/inferior/superior segments of the circular sulcus of the insula, short insular gyri, and long insular gyrus and central insular sulcus); and the left temporal lobe (the temporal pole and polar plane of the superior temporal gyrus) ( Fig. 3 ). The marginal and bivariate probability distributions of average brain-normalized WM fiber bundle length (w ij ) and proportion of GM density lost (g ij ; Fig. 4a–c ) unsurprisingly indicated a considerable number of relatively short connections being affected locally by the presence of the rod while, additionally, a considerable number of longer fiber bundles connecting relatively large regions of cortex were also impacted.

Alterations to these connections contribute to the significant reductions in characteristic path length and mean local efficiency of the remaining network after removal of the affected fibers. That no significant difference was observed concerning the small worldness of the tamping iron network as compared to the intact network suggest that a lesion of this size and scope, while severe, may not had appreciable effects on the degree of clustering of unaffected nodes Mr. Gage's brain relative to randomly degree-equivalent versions of that network. On the other hand, the average simulated lesion did show a significant reduction in small worldness, indicating that regions other than those affected may have more influence over the degree of measured network clustering. Thus, Mr. Gage's unaffected network may have still maintained its small world architecture of nodal clustering and presumed functional integrity, despite loss of major frontal and temporal lobe participation in the system resulting in deficits to measures network integration and segregation.

Several previous articles have precisely investigated the direct effects of node deletions of various size on network connectivity and architecture [33] , [34] , [35] . In particular, the paper by Alstott et al. provides a detailed examination of simulated lesion effects on brain networks both in terms of lesion location and extent. In their study of structural and functional connectivity data from N = 5 healthy subjects, they found that lesions to midline areas resulted in more profound effects on various network metrics than do more lateral brain regions. As might be expected, the magnitude of change was dependent upon the number of nodes removed from the network and the manner in which they were removed. Their observations indicate that networks may be insensitive to lesions involving random node removal or where node removal was based only upon a node's degree of connectedness. However, network lesioning based upon the targeted removal of nodes having high betweenness centrality - a measurement of the number of shortest paths from all vertices to all others which pass through a given node - resulted in greater network vulnerability as evident from significant reductions in global efficiency in contrast to random lesioning. This result is particularly compelling in regards to assessing the robustness of cortical architecture in the face of brain damage to major network hubs localized proximal to the cortical midline.

There is little doubt that a tamping iron injury to central nodes of the frontal lobe would have severely impacted Gage's brain connectivity. Fig. 3 shows the extent of white matter damage and the effects on several measures of network connectivity, including regional betweenness centrality, local efficiency, clustering coefficient, and eccentricity. Note that this illustration differs from Fig. 2 in that the inner-most rings are now colored according to the respective average nodal connectivity metrics in the presence of cortical loss incurred from the tamping iron. Additionally, Fig. 5A illustrates the spatial distribution of these regional connectivity metrics over the cortex when pooled across the intact healthy networks from our sample (sub-cortex not shown). We note that, as observed by Alstott et al., areas of relatively high betweenness centrality tended to be located along the frontal midline. Other metrics show similar regional concentrations ( Fig. 5Aii–iv ). However, while intact frontal areas of both hemispheres show high betweenness centrality ( Fig. 5Ai ), the regions of tamping iron damage encompassed many other regions as well having relatively less betweenness centrality, e.g. TrFPoG/S, RG, SbCaG, TPo. Removal of these areas, as illustrated by the various metric rings in the left frontal segment of the connectogram in Fig. 3 , has wide ranging effects on the regionally-specific network metrics in unaffected brain regions.

It is evident that removal of these areas produce significant effects on global metrics of network segregation and integration. However, from systematic lesion simulation using a similar extent of GM/WM involvement, the effects on Mr. Gage's network integration and segregation were not found to be more severe that that observed from the “average” lesion. Clearly, a larger lesion would have affected a greater number of network nodes including various hubs resulting in further deleterious effects on network integration and segregation. Moreover, a different lesion altogether would have possibly resulted in more outwardly obvious sensorimotor deficits. Located in occipital cortex, for instance, the lesion might have resulted in sensory-specific changes in connectivity (e.g. blindness), or one involving more of the sub-cortex and brain stem could have been more clinically serious and resulted in death. Nevertheless, the observed damage illustrates that severe network insult affecting the majority of left hemisphere connectivity as well as right hemispheric inter-connections, was experienced. Such damage can be expected to have had its influence over the normal functioning of many regions non-local to the injury and their subsequent connectivity as well.

Therefore, in light of these observations, it would be safe to conclude that 1) Mr. Gage's injury very likely destroyed portions of the central hub structure in left frontal midline structures as well as temporal pole and limbic structures which have extensive connectivity throughout the left hemisphere as well as inter-hemispherically, 2) that the tamping iron's passage did not specifically remove only the most central network hubs but a host of regions having a range of network properties, and 3) that such damage to important network hubs connection to other brain regions having secondary levels of centrality, clustering, etc. are likely to have combined to give rise to the behavioral and cognitive symptomatology originally reported by Harlow. Knowledge of Gage's affected connectivity help provide clarity and context for symptomatologies subsequently only inferred by others.

Implications for Gage's Reported Behavioral Changes

Traumatic brain injury of the frontal cortices is often associated with profound behavioral alterations, changes mood [36] , working memory [37] and planning deficits [38] , [39] , social functioning [40] , among other cognitive symptoms [41] , [42] , [43] , [44] . Alterations to functional connectivity have also been reported [45] , [46] which, in addition to cortical damage, likely related to accompanying diffuse axonal injury [47] , [48] . It is also worth noting neurodegenerative diseases, such as the leukodystrophies [49] , Alzheimer's Disease (AD) [50] , [51] , and early-stage frontotemporal dementia (FTD) [52] , also have effects on brain networks involving connectivity of the frontal lobe. Altered structural connectivity in these disorders illustrates changes in large-scale brain network organization deviating from healthy network organization [53] , with possible effects on resting state connectivity [54] . Disruptions of WM connectivity are also known to underlie elements of psychiatric illness [55] , [56] , [57] which are associated with behavioral alterations not dissimilar to those reported in Mr. Gage.

In particular, network damage, predominantly of the left basal forebrain and of its connections throughout the left as well as into right frontal cortices, was particularly extensive. Processing of emotion stimuli have been associated with connectivity of the frontal cortex and amygdala, in particular involving the connectivity of the uncinate fasciculi [58] . Thus, in addition to disinhibition symptoms considered by Damasio et al., with evidence of potentially greater degree of WM rather than cortical injury, there is also similarity between Mr. Gage's behavioral changes and network alterations observed in FTD and related WM degenerative syndromes. This suggests that network topological changes may have been the source of Mr. Gage having not only executive function deficits but also problems resulting from damage to connections associated with the encoding of episodic memory as well as the processing of emotion – consistent with reports on changes in his personality.

Historical Implications of Gage's WM Damage

While observations of severe network damage and their resulting affects may not be surprising given that which has been documented of Mr. Gage's accident and behavioral changes, one can only speculate upon the possible contribution to Gage's survival, recovery, and the uniqueness of changes to his WM networks. Macmillan [3] has noted that many reports on Gage's behavioral changes are anecdotal, largely in error, and that what we formally know of Mr. Gage's post-accident life comes largely from the follow-up report of Harlow [23] according to which Gage, despite the description of him having some early difficulties, appeared to adjust moderately well for someone experiencing such a profound injury. Indeed, the recent discovery of daguerreotype portraits of Mr. Gage show a “handsome…well dressed and confident, even proud” man [59] in the context of 19 th century portraiture. That he was any form of vagrant following his injury is belied by these remarkable images. While certainly neuroanatomically profound, the changes to his cognitive capacities were much more subtle upon his full recovery than may have been otherwise described. In spite of recovering from severe brain trauma, his mental state appears to have eventually stabilized sufficiently for him to travel throughout New England, take on several (some might say menial) forms of employment, travel through South America for several years, and to return to his family in the Western US, before succumbing to epilepsy which was presumably related to the injuries directly affecting his WM connectivity. That his network damage, though extensive, was not apparently more severe than an “average” brain lesion would incur may help to explain his ability to have sufficiently recovered in spite of the residual behavioral changes reported by Harlow.

Limitations of our Study

We have worked to provide a detailed, accurate, and comprehensive picture of the extent of damage from this famous brain injury patient and its effect on network connectivity. While the approach used here to model the tamping iron's trajectory is precise and the computation of average volume lost across our population of subjects is reflective of the acute level of damage, we acknowledge that there was likely more damage than that caused by its presence alone. The iron likely propelled unrecovered bone fragments through the brain. The resulting hemorrhage from the wound was also considerable. Subsequent infection and a large abscess took further toll. Consequently, more GM and WM tissue may have been lost than estimated here. Like Damasio et al. and Ratiu et al. , we make the assumption that Gage's brain and its position within the skull can be estimated from the structure of the skull itself, and that its sub-regions, WM, and connective anatomy can be localized through population averaging. Such a supposition may have its limitations and could be open to debate. Nevertheless, ours represents the best current estimation as to the extent of brain damage likely to have occurred at the level of both cortex and WM fiber pathways. We also have no way of assessing the biochemical cascade of changes to biomarker proteins measureable post-injury in modern TBI patients which may also have influenced the trajectory of Mr. Gage's recovery.

Another potential criticism is that we compare the loss of GM, WM, and connectivity in Mr. Gage by computationally casting the tamping iron through the WM fibers of healthy age- and gender-matched subjects and measuring the resulting changes in network topology. We also systematically lesion the brains of our healthy cohort to derive “average” network metrics and compare the observed values with respect to them – an approach that has been recommended elsewhere [35] . This technique is helpful for creating a representative expectation of inter-regional connectivity against which to compare observed or hypothetical lesions. However, some might consider this approach to be misguided in this instance due to the fact that Mr. Gage's brain was damaged in such a way that he survived the injury whereas a host of other lesions resulting from penetrative missile wounds would likely have resulted in death. Indeed, as noted originally by Harlow, the trajectory of the 110 cm long, 3.2 cm thick, 13 lb. tamping iron was likely along the only path that it could have taken without killing Mr. Gage. Thus, any distribution of lesioned topological values might not provide a useful foundation for comparison because the majority of these penetrative lesions would, in reality, be fatal. We recognize these concerns and the practical implications for subject death which would also be a caveat of other network theoretical applications of targeted or random network lesioning. Indeed, such considerations are something to be taken into account generally in such investigations. Nevertheless, our simulations provide supporting evidence for the approximate neurological impact of the tamping iron on network architecture and form a useful basis for comparison beyond utilizing the intact connectivity of our normal sample in assessing WM connectivity damage. So, while this might be viewed as a limitation of our study, especially given the absence of the actual brain for direct inspection, the approach taken provides an appropriate and detailed assessment of the probable extent of network topological change. All the same, we look forward to further work by graph theoreticians to develop novel approaches for assessing the effects of lesioned brain networks.

Conclusions

In as much as earlier examinations have focused exclusively on GM damage, the study of Phineas Gage's accident is also a study of the recovery from severe WM insult. Extensive loss of WM connectivity occurred intra- as well as inter-hemispherically, involving direct damage limited to the left cerebral hemisphere. Such damage is consistent with modern frontal lobe TBI patients involving diffuse axonal injury while also being analogous to some forms of degenerative WM disease known to result in profound behavioral change. Not surprisingly, structural alterations to network connectivity suggest major effects on Mr. Gage's overall network efficiency. Connections lost between left-frontal, left-temporal, right-frontal cortices as well as left limbic structures likely had considerable impact on executive as well as emotional functions. Consideration of WM damage and connectivity loss is, therefore, an essential consideration when interpreting and discussing this famous case study and its role in the history of neuroscience. While, finally, the quantification of connectomic change might well provide insights regarding the extent of damage and potential for clinical outcome in modern day brain trauma patients.

Ethics Statement

No new neuroimaging data was obtained in carrying out this study. All MRI data were drawn from the LONI Integrated Data Archive (IDA; http://ida.loni.ucla.edu ) from large-scale projects in which subjects provided their informed written consent to project investigators in line with the Declaration of Helsinki, U.S. 45 CFR 46, and approval by local ethics committees at their respective universities and research centers. Research neuroimaging data sets deposited with the LONI IDA and made available to the public are fully anonymized with respect to all identifying labels and linked meta-data for the purposes of data sharing, re-use, and re-purposing. IDA curators do not maintain linked coding or keys to subject identity. Therefore, in accordance with the U.S. Health Insurance Portability and Accountability Act (HIPAA; http://www.hhs.gov/ocr/privacy ), our study does not involve human subjects' materials.

Medical Imaging of the Gage Skull

Medical imaging technology has been applied to the Gage skull on three known occasions to model the trajectory of the tamping iron, infer extent of GM damage, and theorize about the changes in personality which a patient with such an injury might have incurred. In an influential study, Damasio and coworkers [7] used 2D X-rays to obtain the dimensions of the skull itself and to compute the trajectory of the iron bar through the regions of frontal cortex based on independently obtained CT data from a normal subject. Prior to this, CT scanning of the skull had been obtained by Tyler and Tyler in 1982 for presentation and discussion at a neurological scientific meeting. The location of the raw CT data files from this imaging session is unknown but the data were last reproduced in An Odd Kind of Fame (Appendix E), though they were not part of any other scientific publication of which we are aware. The most recent occurrence of scanning on record was performed on June 12 th , 2001 through the Surgical Planning Laboratory (SPL) at Brigham and Women's Hospital, Harvard Medical School. A series of two high-resolution CT image series were obtained of the skull: one covering the portion of the jaw up to approximately the bridge of the nose, and another covering the cranial vault (see details below). These data were used by Ratiu et al. [8] , [60] to digitally reconstruct and animate the passage of the tamping iron through the skull. An additional CT image of the Gage life-mask, a plaster likeness presumed to have been commissioned by Dr. Bigelow during one of Gage's visits to Harvard Medical School, was also obtained and used to create a surface model of Mr. Gage's face, scalp, and neck. New CT or other medical imaging of the skull specimen is unlikely to be performed in the future due to the age and fragile state of the specimen.

Documented Extent of Neurological Damage

In the book An Odd Kind of Fame (2000, pg 85), Macmillan conveniently summarizes the reports from various anatomists on the damage to Gage's brain. We reproduce these summaries here and also add the findings of Ratiu et al. [8] which appeared after the publication of An Odd Kind of Fame .

Skull CT Data Processing

Due to a variety of circumstances, the raw and processed digital imaging data from the 2001 CT imaging session at Brigham and Women's Hospital were improperly archived and effectively lost to science. However, these image volumes were subsequently recovered by the authors and represent the highest quality data/resolution available (0.5 mm slice thickness) for modeling the skull of this noted patient and for use in the modeling of affected anatomy and connectivity. The scan data were originally obtained with the superior, cut portion of the calvarium and the mandible in the correct anatomical position on a Siemens Somatom CAT scanner (Siemens AG, Erlangen, Germany), in the Department of Radiology, Brigham and Women's Hospital (Boston, MA) [8] . These data were converted from ECAT format to the NIFTI file format ( http://nifti.nimh.nih.gov ) using the program “mri_convert” – part of the FreeSurfer neuroimaging data analysis software package (surfer.nmr.mgh.harvard.edu/fswiki/mri_convert). The CT images were systematically segmented and masked by hand using MRICron ( http://www.cabiatl.com/mricro/mricron/index.html ) and seg3D ( http://www.sci.utah.edu/cibc/software/42-seg3d.html ) to isolate the skull cap (the portion of the skull created by its being cut with a saw upon deposition at the Warren Museum by Dr. Harlow), each piece of remaining/healed bone fragments, the left frontal/temporal portion of the skull along the readily evident fracture lines, and the lower jaw, and separate 3-D surface mesh models were generated for each segment using 3D Slicer ( http://www.slicer.org ). An additional binary image volume was created by hand-filling the space of the cranium that contained Gage's brain. This volume represents a digital version of the standard endocast often used in the analysis of paleontological specimens [61] , [62] , [63] . Use of the Gage skull and life mask CT data is courtesy of the SPL and the Warren Anatomical Museum at Harvard Medical School.

The LONI Pipeline Workflow Environment

For all major image processing operations (e.g. bias field correction, skull stripping, image alignment, etc.) we employed the LONI Pipeline Workflow Environment ( http://pipeline.loni.ucla.edu ; Fig. S1 ). This program is a graphical environment for construction, validation, and execution of advanced neuroimaging data analysis protocols. It enables automated data format conversion, leverages Grid computer systems, facilitates data provenance, and provides a significant library of computational tools [64] , [65] , [66] .

For instance, employing LONI Pipeline, we used the Brainsfit software package ( http://www.nitrc.org/projects/multimodereg/ ) to register the T1 anatomical MRI volumes to the endocast template. Diffusion gradient image data were processed in native subject space using Diffusion Toolkit ( http://trackvis.org ) to reconstruct the fiber tracts. Data processing workflows to compute inter-regional connectivity matrices were constructed using purpose-built software. Fig. S2 illustrates an example connectivity matrix displayed using Matlab (Mathworks, Natick, MA, USA).

Measurements of the Skull

Consistent with Damasio et al. , the physical dimensions of the Gage skull were measured as follows in Table 2 using the Slicer software program. Additionally, the following landmarks were identified on the Gage skull: Entrance of the Left Auditory Canal: (49.56, 219.46, −807.75 mm); Entrance of the Right Auditory Canal: (175.04, 212.26, −802.85 mm); and the Middle of Crease Between Frontal Bone Plate and Nasal Bone: (117.04, 301.73, −800.72 mm). Given these landmarks, all the other points can be accurately positioned.

Measurements of the Tamping Iron

One of our team (MCC) visited the Warren Anatomical Museum and, working with lead curator Dominic Hall, obtained the following measurements of the iron using a SPI Digimax caliper (Model: 30440-2): 110 cm in length, 9.5 cm circumference, and 2.88 cm diameter at tail. The rear taper is approximately 19 cm long, the maximum diameter (between the rear and tip taper) is 10.5 cm circumference (3.2 cm diameter), the taper beginning at the tip is 27 cm long, and the diameter at the rod's tip is 72 mm.

The Trajectory of the Tamping Iron

The trajectory of the tamping iron through Mr. Gage's skull and brain has been the subject of much debate and several attempts have been made to infer the relationship between putative damage on the one hand and the lore surrounding Gage's personality and behavioral changes resulting from his accident on the other. Bigelow [67] first attempted to formally model the trajectory of the rod by drilling a hole through another “common” skull (pg. 21), and noted that “a considerable portion of the brain must have been carried away; that while a portion of its lateral substances may have remained intact, the whole central part of the anterior lobe, and the front of the sphenoidal or middle lobe must have been lacerated and destroyed”. Importantly, Damasio [7] and coworkers provided a detailed analysis of the rod trajectory through the skull attempting to identify which brain regions were impacted by the flight of the iron and what effect this impact had on the patient's post-injury behavior. While this study has been well cited, their methodology for determining the rod trajectory has been subsequently questioned [3] .

Ratiu et al. [60] constrained their modeling of the rod trajectory by noting bony injuries to the skull, and by more closely aligning the rod with the clinical information provided by both Harlow and Bigelow. Ratiu et al. inserted the brain of a single normal subject into Mr. Gage's cranial cavity to examine which structures might have been affected. Their reconstruction shows that the path of the iron passed left of the superior sagittal sinus (their Fig. 4b,d ). This is corroborated by the fact that damage to the superior sagittal sinus would have almost certainly caused air embolism and/or significant blood loss, resulting in Mr. Gage's death. In addition, their reconstruction shows, in their normal subject's brain, that the iron's trajectory was also anterior to the cingulate gyrus and to the left lateral ventricle (their Fig. 4 e,f ). No rhinoliquorhea or other indication of post-traumatic CSF fistula was reported, nor that Gage developed ventriculitis, a condition which very likely would have been lethal - especially in the 1840's before the use of antibiotics in common medical practice. However, there is little way of being empirically precise with respect to location of major structures when employing only a single, example subject to represent Mr. Gage's unknown neuroanatomy.

To address this issue, we fit the T1 anatomical and diffusion images from the N = 110 normal, right handed subjects, aged 25–36 into the space of Phineas Gage's cranial vault to map the probability to regional injury and the effects of the tamping rod on WM fiber connectivity. The process of morphing data into the Gage skull is described in the following sections.

Determining the Trajectory of the Tamping Iron

Using the measurements of the original tamping iron [3] , [8] , [24] , [67] , on display at the Warren Museum, a 3-D model of the tamping iron was generated using Matlab and stored as an VTK surface ( http://www.vtk.org ) for visualization using 3D Slicer and for processing using the segmented brain regions and fiber tracts morphed into the space of the Gage 3D cranial endocast volume model.

To constrain the trajectory of the rod through the Gage skull, we examined the work of previous authors to identify noteworthy statements on the condition of the skull, particular patterns of breakage, chips in the bone, and other prominent features that could be used as landmarks to restrict the possible paths which the rod might have taken ( Fig. S3 ). For instance, the left maxillary molar is missing and osteological analysis by the Warren Museum states that it was lost ante-mortem (Object File WAM 00949, Warren Anatomical Museum, Francis A. Countway Library of Medicine). While Harlow and/or Bigelow do not specifically mention the loss of this tooth, it is likely that the rod made contact with it after passing through Gage's cheek, and was either dislodged completely or knocked loose and lost sometime during his recovery. Additionally, for the zygomatic arch the Warren Museum records (also WAM 00949) indicate “Maxilla: ante-mortem sharp force trauma remodeling” but are not more specific about the potential for complete breakage of the zygomatic process which was suspected by Ratiu et al. Still, it can be assumed that some contact was made between the iron and the interior portions of the arch. A collection of previously reported observations contributing to the set of applied constraints are noted in Table 3 .

In particular, we concur with Ratiu et al. that Mr. Gage had his jaw open at the moment of the accident. Harlow reports Gage looking over his right shoulder and saying something to his crew at critical moment of the blast. In the casting of possible rod trajectories, the most likely position of the jaw was determined to be −15° in pitch (downward) and 5° in yaw (to the right) relative to the closed position of the jaw. This position allowed the unhindered passage of 1.303×10 3 out of 1×10 9 viable rod trajectories inclusive through the skull. With this jaw position, in contrast to the suspicion of Bigelow, we noted no contact between the rod and that of Mr. Gage's coronoid process. Jaw rotations at greater pitch angles were inconsequential to our results. Therefore, these values represent the minimal angular jaw deflections needed to allow the maximal number of rod passage scenarios without jaw intersection. Additionally, these values are typical for the acts of speaking and mastication in which the maximum typical jaw pitch extension in males is ∼30° [68] . Assuming the jaw to be in a completely closed position forces rod trajectories to incline more toward the right hemisphere in order to avoid contact with the jaw and breaking it - as may result from the trajectories identified by Damasio et al. Having the jaw open provides a greater number of possible paths which are closer to the vertical axis, which thus does not enforce an intersection of the rod with the right hemisphere ( Fig. S4A , B, D; Fig. S5 A–D). The rod's intersection with white matter fiber tractography was thereby determined ( Fig. S6 ). Movie S1 illustrates the path of the tamping iron through Mr. Gage's skull and the white matter fiber pathways of his left hemisphere.

Normal Subjects

T1 anatomical MRI and 64-direction diffusion tensor images (DTI) from N = 110 right-handed male subjects between the ages of 25 and 36 were selected from the LONI Integrated Data Archive (IDA; http://ida.loni.ucla.edu ). The age range was specifically selected to match the age at which Mr. Gage received his injury (25 years old) as well as the age at which he succumbed as a presumed result of the brain damage he experienced (36 years old). Subjects were all healthy “normals” with no neurological or history of psychiatric illnesses.

Segmentation and Parcellation

Segmentation and regional parcellation were performed using FreeSurfer [69] , [70] , [71] following the nomenclature described in [72] . For each hemisphere, a total of 74 cortical structures were identified in addition to 7 subcortical structures and to the cerebellum. The 82 cortical and sub-cortical label names were assigned per hemisphere to each brain based upon the nomenclature described in Destrieux et al. [72] . Regional parcellation was performed using FreeSurfer [73] , [74] , [75] , [76] (see also above). The numbers of hemispheric partitions in the segmentation was as follows – frontal (21), insula (8), limbic (8), temporal (12), parietal (11), occipital (14), basal ganglia (8), and brain stem (1). The complete coding scheme is as presented describing the parcellation scheme naming convention ( Table 6 ) and their abbreviations ( Table 7 ), which can be used to identify the regional labels in Figs. 2a and and3 3 .

Connectogram Design

Neuroanatomical structure and connectivity information were graphically depicted in a circular diagram format using freely available Circos software ( [77] , www.cpan.org/ports ). Briefly, Circos is a cross-platform Perl-based application which employs a circular layout to facilitate the representation of relationships between pairs of positions by the use of various graphical elements, including links and heat maps. While traditionally used to render genomic information, Circos can be effectively adapted to the exploration of data sets involving complex relationships between large numbers of factors. In our case, cortical parcellations were represented as a circular array of 165 radially aligned elements representing the left and right cerebral hemispheres, each positioned symmetrically with respect to the vertical axis. We term this representation a “connectogram”. The brain stem was positioned at the most inferior extremity of the Circos ring as a consequence of its inclusion as the only midline structure. In this manner, Circos' ability to illustrate chromosomes was modified for lobar depiction, while its functionality for illustrating cytogenetic bands was modified to represent cortical parcellations. As previously described, each parcellation was assigned an arbitrary but unique RGB color (see below). Parcellations were arranged within each lobe in the order of their location along the antero-posterior axis of the cortical surface associated with the published FreeSurfer normal population atlas [72] . To determine this ordering, the center of mass was computed for the GM surface portion associated with each parcellation, and the order of all parcellations was determined based on the locations of these centers of mass as their distance from the frontal pole increased along the antero-posterior coordinate axis. A LONI Pipeline workflow for the creation of the connectogram images using parcellation and connectivity matrix information is available upon request from the authors. A complete description of the methods for connectogram construction can be found in [78] with applied examples in [79] .

Color Coding Schemes

Each cortical lobe was assigned a unique color scheme: black to red to yellow (Fro), charlotte to turquoise to forest green (Ins), primrose to lavender rose (Lim), pink to lavender to rosebud cherry (Tem), lime to forest green (Par), and lilac to indigo (Occ). Each structure was assigned its unique RGB color based on esthetic considerations; e.g. subcortical structures were colored light gray to black. Color scheme choice and assignment to each lobe were made by taking into account the arrangement and adjacency of lobes on the cortical surface, with the goal of avoiding any two adjacent lobes from having overlapping or similar color schemes which were too similar. The individual colors of the scheme associated with any particular lobe were assigned to every parcellation within that lobe in such a way as to create a distinct contrast when displayed on cortical surfaces ( Fig. S2 ) or on the connectogram graphics ( Figs. 2 and and3). 3 ). The particular regional color mappings employed in this article can be considered arbitrary and are not intended to convey any universal or standard regional color scheme, per se .

Representation of Cortical Metrics

Within the circular framework representing the cortical parcellations, five circular heat maps were generated, each encoding one of five structural measures associated with the corresponding parcellation. Proceeding inward towards the center of the circle in Fig. 2 , these measures were: total GM volume, total area of the surface associated with the GM-WM interface (forming the base of the cortical ribbon), mean cortical thickness, mean curvature and connectivity per unit volume. For subject-level analysis, these measures were computed over the entire volumetric (or areal, as appropriate) extent of each parcellation; for the population-level analysis, they were averaged over all subjects.

Values for each measure were mapped to colors, using a scheme that ranged from the minimum to the maximum of the data set. For example, the cortical thickness t with values ranging from t min to t max was normalized as t 1 = ( t − t min )/( t max − t min ). The latter value was mapped onto a unique color from the color map of choice. Thus, for example, hues at color map extremities correspond to t min and t max , as required. For subcortical structures, brain stem and cerebellum, three measures (area, thickness and curvature) were unavailable on a parcellation-by-parcellation basis; their corresponding heat map entries were consequently left blank.

The connectogram in Fig. 3 , illustrating the effects of the tamping iron lesion, represents the individual regionally-specific network metrics (i.e. betweenness centrality, eccentricity, mean local efficiency, and clustering coefficient) and are colored distinctly to be consistent with the cortical maps of the same but unaffected network metrics presented in Fig. 5A . The inner-most ring of the connectogram in Fig. 3 represents the average proportion of regional GM loss taken across subjects.

Connectivity Calculation

To compute connectivity between regions for each subject, the location of each fiber tract extremity within the brain was identified, while the GM volume associated with each parcellation was also delineated. For those fibers which both originated as well as terminated within any two distinct parcellations of the 165 available, each fiber extremity was associated with the appropriate parcellation. For each such fiber, the corresponding entry in the connectivity matrix (e.g. Fig. S2 ) of the subject's brain was appropriately updated to reflect an increment in fiber count [80] , [81] . Each subject's connectivity matrix was normalized over the total number of fibers within that subject; for population-level analysis, all connectivity matrices were pooled across subjects and averaged to compute probabilistic connection probabilities.

Connectivity Representation

For subject-level connectograms, links were generated between any two parcellations whenever a WM tract existed between them. In population-level analyses, the former was done whenever there was a non-vanishing probability for a WM tract to exist between the two regions ( Fig. 2 ). Links were color-coded by the average fractional anisotropy (FA) value associated with the fibers between the two regions connected by the link, as follows. The lowest and highest FA values over all links ( FA min and FA max , respectively) were first computed. For any given connection i where i = 1, …, N ( N being the total number of connections), the FA value FA i associated with that connection was normalized as FA′ i = ( FA i − FA min )/( FA max − FA min ), where the prime indicates the FA i value after normalization. After this normalization, FA′ i values were distributed in the interval 0 to 1, where 0 corresponds to FA min and 1 corresponds to FA max . The interval 0 to 1 was then divided into three subintervals (bins) of equal size, namely 0 to 1/3, 1/3 to 2/3, and 2/3 to 1. For every i = 1, …, N , link i was color-coded in either blue, green or red, depending on whether its associated FA′ i value belonged to the first, second, or third bin above, respectively. Thus, these bins represent low, medium, and high FA. In addition to encoding FA in the link's color as described, relative fiber density (the proportion of fibers for each connection out of the total number of fibers) was also encoded as link transparency. Thus, within each of the three FA bins described, the link associated with the highest fiber density within that bin was rendered as completely opaque, whereas the link with the lowest fiber density was colored as transparent as possible without rendering it invisible. For example, the link with FA′ i = 1/3 was colored as opaque blue, whereas the link with the lowest FA′ i value was colored as most transparent blue. Similarly, the link with FA′ i = 2/3 was colored as opaque green, and the link with the lowest value of FA′ i greater than 1/3 was colored as faintest green. The links associated with the lowest fiber densities were drawn first, and links with progressively larger relative fiber densities were drawn on top of the former. The process was successively repeated by drawing links with higher fiber densities on top of links with lower fiber densities. Thus, links associated with the largest fiber densities were drawn “on top” of all other links.

Representation of Connectivity Affected by Pathology

Links associated with fibers affected by pathology were designed to encode fiber density using the same transparency coding scheme as described in the previous subsection. In contrast with the case of healthy fibers, however, two different color schemes were used to encode pathology. Whenever fibers existed between one cortical region that was affected by pathology and another that was not, the color used to draw the corresponding link was brown. By contrast, links between parcellations that were both affected by pathology were drawn using the color gray. This allows one to visually distinguish between connections that involve only one affected region (brown links) and connections that involve two regions that were both affected (grayscale links) ( Fig. 3 ).

Calculation of Pathology Effects upon GM/WM Volumetrics

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The calculation described above estimated the amount of GM that was directly affected by the passage of the rod. To compute the total amount of GM that was affected by pathology, however, it is not sufficient to compute the sum of directly lesioned GM parcellation volumes because pathology-affected GM includes cells with intact somas whose axons were nevertheless injured in at least one location along their paths. In other words, a population of neurons whose GM axons were destroyed or affected in spite of their somas being outside the volume of direct injury should also be taken into account when computing the amount of affected GM. Furthermore, the destruction of fibers originating in some parcellated region r 1 that had been directly affected by pathology could also have affected the GM in parcellations to which r 1 is connected by WM fibers originating in r 1 . Consequently, an appropriate calculation of the total GM volume affected by pathology must take into account available quantitative information concerning the extent to which WM fibers affected by pathology could indirectly affect GM as well. To obtain and interpret such information meaningfully, one can use the measures of GM and WM atrophy described below:

Let c ij ( h ) be the probabilistic count of fibers between parcellated regions r i and r j , as computed over all healthy subjects using the methods described in the section on Connectivity Calculation . Note that c ij ( h ) is the connectivity matrix entry which specifies, in a probabilistic sense, the proportion of fibers between parcellated regions r i and r j . The dependence of the count c ij upon the parameter h (denoting health) reflects the fact that the fiber density can be different depending on whether the parcellated region has or has not been affected by pathology. For the former scenario, the count is denoted by c ij ( p ), where p stands for pathology. If two parcellations r i and r j , are unaffected, then

If, however, either one or both of r i and r j are affected, then

where c ij ( d ) stands for the count of fibers that were destroyed (hence d as the argument) as a result of the injury. The change in fiber count from health to pathology between two regions untouched by the rod reflects the extent to which the somas of the neurons connecting the regions have been affected by direct injuries to the WM fibers between them. Consequently, it is reasonable to posit that an appropriate measure of GM injury in this case can be formulated by relating the proportion of destroyed WM fibers between two regions to the proportion of affected GM volume within the regions. For this purpose, we computed the metric

Histological research [82] (and references therein) indicates that the constant of proportionality can be assumed to be approximately equal to 1, i.e.

This relationship is useful because, whereas calculation of the ratio on the LHS is straightforward from DTI tractography as previously described, that of the ratio on the RHS is not because regions r i and r j do not necessarily intersect the passing rod.

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A second metric of interest is the ratio

Average Percentages of Brain Regions Intersected by the Rod

The average percentage regional volumes (and their standard deviations) intersected by the rod pooled over N = 110 subjects are listed in Table 7 and illustrated graphically in the connectogram of Fig. 3 .

Network Analysis

Because network theory can provide essential insight into the structural properties of cortical connectivity networks in both health and disease [83] , several network metrics of particular significance were computed for each subject, starting with the degree of each node. In our case, nodes were denoted by parcellated regions and edges were represented by fiber tracts. Nodal degree is the number of edges connected to a node and its calculation has fundamental impact upon many network measures; moreover, node degree distributions are highly informative of network architecture. The entry indexed by i and j in the distance matrix of the graph contains the minimum weighted physical length of the path connecting vertices i and j and was computed using the algebraic shortest paths algorithm [84] . Degree of connectivity is represented as the inner-most ring in Fig. 2 , though was not analyzed further beyond its being utilized in the computations of some of the overall network metrics detailed below.

The measurement of network attributes can be generally broken down into the examination of overall network integration – the measurement of path lengths between nodes in a network and the extent of network-wide interaction and ease of communication between distinct regions; segregation – the extent to which nodes of the network group themselves into separate communities; and small worldness – the quantification of the generally shorter path lengths and higher clustering observed in many biological and technological networks with respect to randomly connected systems [85] . To specifically measure these overall network properties, we chose to focus on three particular metrics. To assess network integration from each subject's connectivity matrix we measured the characteristic path length, a measurement of the global average of a graph's distance matrix [86] . Appropriate to our application, the weighted characteristic path length of a network may be altered as a result of brain trauma [87] . To measure the degree of segregation, we computed the mean local efficiency of each network. Investigating network segregation can be important because it can reveal how much information brain regions are able to exchange as well as the extent to which such regions remain structurally segregated from each other. In this instance, reduced efficiency might be expected as a result of a severe penetrating head wound. Finally, we measured network small worldness , i.e. the ratio comprised of the observed characteristic path length relative to that observed in a random network having the same degree distribution and the observed clustering coefficient relative to that observed in a random network.

Additionally, to characterize the regionally-specific effects of the tamping iron lesion, we also computed several additional graph theoretical measurements for each parcellated brain region. These included 1) betweenness centrality, measuring the number of shortest paths from all vertices to all others that pass through that node, 2) local efficiency, the mean shortest absolute path length of at that node, 3) clustering coefficient, measuring the degree to which a node is nodes in a graph is a member of a cluster or clique, and 4) eccentricity, representing the greatest geodesic distance between that node and any other vertex in the graph. Metrics were computed for each subject and averaged with respect to weighting by subject-wise regional parcellation volume. To be consistent with other studies reporting these regionally-specific values, we chose not to normalize them with respect to those obtained in equivalent random networks. Averages of these metrics are illustrated in Fig. 5a(i–iv) along with linear colorbars indicating the ranges of observed mean values. Effects on these metrics in the presence of the tamping iron can be seen as the first four of the inner-most rings of the connectogram presented in Fig. 3 .

Several additional global as well as local graph metrics were computed but not reported here due to potentially excessive colinearlity, imprecision, or due to recognized difficulty with interpretation. For instance, network modularity [88] was not considered due to the heuristic nature of its computation and tendency to provide unreliable values upon repeated estimation. While many of these other network metrics are well known and have their unique advantages [83] , the ones chosen parsimoniously capture the overall changes in network architecture for this patient and the extent to which his injury would compare to similarly-sized lesions in other areas of the cortex. The Brain Connectivity Toolbox (BCT; https://sites.google.com/a/brain-connectivity-toolbox.net/bct/Home ) was used for all weighted and unweighted connection density- and path-length related graph theoretical computations [84] .

For each of the global graph theory measures described above, the mean and standard deviation was computed for each subject in both intact (healthy) and pathology-affected scenarios (the tamping iron lesion as well as simulated lesions over the brain). As an additional basis, we also performed a degree-preserving randomization process using the BCT for each subject's intact network, computed the aforementioned network measurements, and report these averaged across subjects. Such normalization has been recently advised by Rubinov and Sporns [84] . In our case, this involved 10,000 “rewiring” iterations of the BCT null_model_und_sign (compiled C-code version of the Matlab code from the “the bct-cpp project”; http://code.google.com/p/bct-cpp ) algorithm per region by subject. To accommodate the computational cost of performing such a randomization process, we utilized fully the 1200 node Linux cluster based at the Laboratory of Neuro Imaging (LONI) at UCLA to randomize subjects and regions in parallel. Incidentally, normalization of each network type by its own randomized version has the effect of scaling out differences between networks – lesioned or otherwise – and thus makes the metrics largely insensitive to the effects of network damage. So, to provide a common frame of reference across each network type, the observed metrics for the intact, tamping iron, and simulated lesions were normalized with respect to the degree-preserving randomization of the intact network. Finally, to specifically test the differences between the intact and the tamping iron-lesioned networks between subjects, paired Student's t-tests were applied for each normalized measure to identify significant differences between means at p≤0.01. Results are summarized in Table 5 . Further details on the lesion simulation are provided in the section below.

Equivalent Lesion Simulation and Comparison

To examine the tamping iron lesion's specificity to changes in network structure, we investigated whether changes Gage's brain network properties were significantly different from those that would be expected by chance for the same amount of GM loss located in other regions of the brain. To address this, network properties were computed for a set of simulated lesions systematically positioned over the cortex (excluding the tamping iron lesion itself) and Mr. Gage's network measurements were compared to the distribution of the average metric values taken over subjects and lesions. Specifically, we adopted an approach similar to that of Alstott et al. [89] , who simulated the effects on functional connectivity of targeted lesions distributed in various regions of the cerebral cortex. In our extension of this method, localized area removal was performed by deleting all nodes and their connections within regions consisting of contiguous anatomic parcellations as defined using the methods of Destrieux et al. [72] . In contrast to Alstott et al., however, our structural connectivity simulations also sought to account for additional lesion effects upon WM by modeling the removal of so-called “fibers of passage”. To do so, connectivity network edges between anatomic parcellations neighboring the GM lesion were removed without deleting the corresponding nodes connected by these edges, unless these nodes also belonged to the GM portion of the lesion itself.

The details of our simulation are as follows: 500 distinct lesions were simulated by first populating the cortical surface with 500 distinct sets of contiguous parcellations. Each of these sets was subsequently used as a synthetic “lesion”, subject to the constraints that the percentages of WM and GM lost due to the lesion were the same as had been estimated for Gage's tamping iron injury. This process was repeated until 500 distinct lesions were created uniformly across the brain, and the procedure was repeated for all 110 subjects included in the study. To ensure that each of the lesions had approximately the same position in each subject, lesion configurations were defined using the cortical atlas of Fischl, Dale et al. [71] , and the corresponding location of every lesion in each subjects was identified by mapping the lesion configuration from the atlas to each subject's cortical surface using existing/published FreeSurfer methodology [70] , [90] , [91] . Thus, by the process described above, 500 distinct lesions that were identical in size to Gage's from the standpoint of percentage WM and GM loss were created uniformly over the brain in each of the 110 subjects. Subsequently, each lesion's effect on overall network properties was computed. Global network metrics were then pooled over all subjects and simulations so as to obtain the average (i.e. most probable) value of every metric for each of the 500 simulated lesioned networks.

In this context, for each network metric, the null hypothesis was formulated as the statement that the metric value associated with Gage's lesion of left frontal cortex was drawn from the same distribution as that of the “average” cortical lesion. This comparison of changes in network properties as a function of lesion location is one viable and interesting way to assess whether Mr. Gage's brain network properties were significantly different from those that would be expected by chance for the same amount of GM and WM loss. Specifically, for each metric m , the whole brain mean μ ( m ) and standard deviation σ ( m ) of the metric was first computed over lesions. Subsequently, for the metric value m T associated with each lesion, the standard score

was computed. Results for the average properties in the intact networks, the tamping iron injury, and the lesion simulations – in addition to their degree-preserved randomized comparison versions - are illustrated in Fig. 5b (i and ii) . Similar calculations and comparisons on the basis of small worldness provided patterns highly similar to that for network integration, thus were deemed redundant, and therefore are not illustrated here.

Finally, we compared the observed effects of the tamping iron lesion on the random network normalized graph theory measures of integration and segregation against that observed for all remaining lesions. Computed as Z-statistics, the results of these comparisons are illustrated graphically for network integration and segregation in Fig. 5c (i and ii) , respectively, and are colored to show those effects most similar to the tamping iron lesion (black), moderately similar (orange), and most dissimilar (white). Generally, as one moves posteriorly away from the Gage lesion site, similarity on network effects tends to be reduced. However, exceptions exist in bilateral post-central gyrus and the left superior and posterior portion of the parahippocampal gyrus.

Supporting Information

The LONI Pipeline Workflow Environment. We applied the LONI Pipeline [93] , [94] for segmentation and registration of the input MRI image volume data, the processing of all DTI tractography, and computation of tract statistics. This grid-based solution provides validation and distribution of new computational tools, and an intuitive graphical interface for developing and executing parallel volumetric processing software. See http://pipeline.loni.ucla.edu for additional details.

Views of the cortical parcellation of a sample subject. Top rows show the lateral, anterior, and dorsal surfaces; second row shows medial, posterior, and ventral pial surfaces, while the bottom two rows show the same orientations but as inflated pial surfaces to more adequately present the extent of regional parcellations and their color coding. The arbitrarily chosen regional colors are the same as those of the outer-most ring in Figure 2 and whose RGB values are referenced Table 5 are shared by the outer most ring of brain regions on the connectogram images permitting rapid cross-reference.

Connectivity Matrix. Each row and each column represent distinct parcellated regions where in each cell i,j was computed the number of fibers that were found to begin or end in each region pair, the average FA, and the average fiber length over subjects.

Modeling of the Skull Fragmentation and the Rod. a) Models of the eyeballs were placed in to the ocular cavities in order to use them as constraints for the trajectory of the tamping iron. According to Harlow's account, the left orbit was extended outward “by half its diameter”. b) The bones of the skull representing the major breakages were systematically labeled and can be independently manipulated using Slicer. The mandible was also rotated downward and laterally in order to allow the tamping iron not to impinge on it and also to comply with Harlow's account that Gage was in the act of speaking to his men at the moment of the blast. c) The surface model of the Gage skull, with closed mandible, along with the surface of the life mask commissioned by Bigelow. d) A view looking superiorly along the tamping iron's computed trajectory noting how the iron displaced the left anterior frontal bone as it passed.

Illustrating the Intersection of the Rod and the Brain. a) A figure showing the passage of the rod through the skull with the bones above the cranial “cap” cut at Harlow's direction, and its intersection with the left anterior white matter fiber pathways of an example subject. The complementary hemisphere is displayed to illustrate that the rod did not intersect that hemisphere. b) A view of the rod displacing the bones of the skull. c) A close up, coxial view of the inferior portion of the iron along its trajectory. d) The intersection of the tamping iron with the left frontal cortex with each major bone fragment removed.

The Effects of the Tamping Iron on White Matter Fiber Tractography. a) A view of the Gage skull with the white matter fiber tracts of an example subject warped to the space. In this view, fibers which intersect the rod's pathway have been removed. b) A transaxial view of the DTI fiber pathways remaining after those which were intersected by the rod had been removed. c) The fibers intersected by the rod connect areas of cortex throughout the left cerebral hemisphere as well as between hemispheres. d) A sagittal view of the fibers experiencing damage by the tamping iron. All bone fragments and the cranial “cap” have been removed.

Movie of The Effects of the Tamping Iron on White Matter Fiber Tractography. This movie rendering illustrates the passage of the tamping iron through the Gage skull and its intersection with left hemispheric white matter fiber pathways. The right hemispheric cortical surface model is displayed to illustrate that the rod did not cross the midline to damage right frontal cortex. The rendering was created using 3D Slicer ( http://slicer.org ).

Acknowledgments

The authors wish to acknowledge the assistance of Dominic Hall, Curator, Warren Anatomical Museum, Center for the History of Medicine, Francis A. Countway Library of Medicine 10 Shattuck Street, Boston, MA 02115 for access to Mr. Gage's skull, life mask, and tamping iron. We also express our gratitude to Marianna Jakab of the Surgical Planning Laboratory at Harvard Medical School for assistance with the CT image volumes, and to Drs. Danielle Bassett (Department of Physics, University of California Santa Barbara), Randal McIntosh (Rotman Institute, Toronto, Canada), and Paul M. Thompson (Department of Neurology, University of California Los Angeles) for their input and guidance on our network theoretical analyses. We are also extremely grateful for the rigorous and thorough comments of two anonymous reviewers on earlier versions of this article. Finally, we are indebted to the dedicated staff of the Laboratory of Neuro Imaging (LONI) at UCLA.

Competing Interests: The authors have declared that no competing interests exist.

Funding: This work was supported by 2U54EB005149-06 “NAMIC: Traumatic Brain Injury - Driving Biological Project” to JVH, 1RC1MH088194 “Informatics Meta-Spaces for the Exploration of Human Neuroanatomy” to JVH, and P41RR013642 “Computational Anatomy and Multidimensional Modeling” to AWT. This work was performed as part of the Human Connectome Project (HCP; www.humanconnectomeproject.org ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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1.3: The Case of Phineas Gage- Connecting Brain to Behavior

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Learning Objectives

Discuss the Case of Phineas Gage and its contribution to biological psychology.

While experiments are necessary to establish cause and effect relationships, in-depth studies of unique individuals or groups of people who share an experience can be used to inform our understanding of things that we can not study experimentally. Surgical errors, extreme mistreatment, and tragic accidents are impactful events that can alter individuals significantly, providing unique opportunities to study the effects of experiences which can not be ethically studied experimentally. There have been a number of these case studies which have revealed the role of different parts of the brain on our thinking and behavior. One such case is Phineas Gage. Gage lived 12 years after a rod pierced his skull, damaging his left frontal lobe. Researchers were able to gather information about his functioning before and observe his cognitive ability and personality after the accident. His case enabled the field to understand the role of frontal lobe in personality and mental processes.

The Tale of Phineas Gage

Phinease Cage after his accident, holding the rod that damaged his brain

The case of Phineas Gage is worthy of expanded coverage as his tragic accident establishes a clear connection between the brain and who we are. Gage, a 25-year-old man, was employed in railroad construction at the time of the accident. As the company's most capable employee, with a well-balanced mind and a sense of leadership, he was directing a rock-splitting workgroup while preparing the bed of the Rutland and Burlington Railroad south of Cavendish, Vermont, USA. At 4:30 PM on September 13, 1848, he and his group were blasting a rock, and Gage was assigned to put gunpowder in a deep hole inside it.

The moment he pressed the gunpowder into the hole with a bar, the friction caused sparks, and the powder exploded. The resulting blast projected the meter-long bar, which was 1.25 inches in diameter and weighed about 13.2 pounds, through his skull at high speed. The bar entered his left cheek, destroyed his eye, passed through the left front of his brain, and left his head at the top of the skull on the right side. Gage was thrown on his back and had some brief convulsions, but he woke up and spoke in a few minutes, walked with a little help, and sat in an ox cart for the 0.7-mile trip to where he was living.

About 30 minutes after the accident, a doctor arrived to provide medical care. Gage had lost a lot of blood, and the next days that followed were quite difficult. The wound became infected, and Phineas was anemic and remained semi-comatose for more than two weeks. He also developed a fungal infection in the exposed brain that needed to be surgically removed. His condition slowly improved after doses of calomel and beaver oil. By mid-November he was already walking around the city.

The Consequences

For three weeks after the accident, the wound was treated by doctors. During this time, he was assisted by Dr. John Harlow, who covered the head wound and then reported the case in the Boston Medical Surgery Journal. In November 1849, invited by the professor of surgery at Harvard Medical School, Henry Jacob Bigelow, Harlow took Gage to Boston and introduced him to a meeting of the Boston Society for Medical Improvement .

In his reports, Harlow described that the physical injury profoundly altered Gage's personality. Although his memory, cognition, and strength had not been altered, his once gentle personality slowly degraded. He became a man of bad and rude ways, disrespectful to colleagues, and unable to accept advice. His plans for the future were abandoned, and he acted without thinking about the consequences. And here was the main point of this curious story: Gage became irritable, irreverent, rude and profane, aspects that were not part of his way of being. His mind had changed radically. His transformation was so great that everyone said that “Gage is no longer himself.”

As a result of this personality change, he was fired and could no longer hold a steady job. He became a circus attraction and even tried life in Chile, later returning to the United States. However, there is something still little known about Gage: his personality changes lasted for about four years, slowly reverting later. As a proof of this, he worked as a long-haul driver in Chile, a job that required considerable planning and focus skills. He died on May 21, 1861, 12 years after the accident, from an epileptic seizure that was almost certainly related to his brain injury.

After his body was removed from its grave, Gage's mother donated his skull to Dr. Harlow who in turn donated it to Harvard University.

Gage's case is considered to be one of the first examples of scientific evidence indicating that damage to the frontal lobes may alter personality, emotions, and social interaction. Prior to this case, the frontal lobes were considered silent structures, without function and unrelated to human behavior. Scottish neurologist, David Ferrier, was motivated by this fact to investigate the role of frontal lobes in brain function. Ferrier removed the frontal lobes in monkeys and noted that there were no major physiological changes, but the character and behavior of the animals were altered. In other words, he confirmed the role of the frontal lobes that was suggested by Gage's accident in an experiment with a non-human animal.

Knowledge that the frontal lobe was involved with emotions continued to be studied. The surgeon Burkhardt in 1894 performed a series of surgeries in which he selectively destroyed the frontal lobes of several patients in whom he sought to control psychotic symptoms, being the modern prototype of what was later known through Antonio Egas Moniz as psychosurgery. Today, it is well understood that the prefrontal cortex of the brain controls the organization of behavior, including emotions and inhibitions.

Folkloric as it may be, but nonetheless remarkable, the contribution of Phineas Gage's case should not be overlooked, as it provided scientists the baseline for the promotion of studies in neuropsychiatry, and a source of inspiration for world medicine. In 2012, a team of neuroscientists used computer tomography of Gage's skull with typical brain MRI scans to simulate how extensive Gage's brain damage was. They confirmed that most of the damaged area was the left frontal lobe. However, surrounding areas and their neural network were also extensively severed. And it is not just the researchers who keep coming back to Gage. Medical and psychology students still learn about Gage from their history lessons. Neurosurgeons and neurologists still sometimes use Gage as a reference when evaluating certain cases. The final chapter of his life also offers us a thought-provoking discovery about cases of massive brain damage, indicating that rehabilitation may be possible.

Phineas Gage made a huge contribution to our understanding of the frontal lobe damage and its subsequent change in personality. Furthermore, his case expanded knowledge in neurology in several areas, including the study of brain topography in behavioral disorders, the development of psychosurgery, and finally the study of brain rehabilitation. Also, Gage's case had a tremendous influence on early neuropsychiatry. The specific changes observed in his behavior pointed to theories about the localization of brain function and correlated with cognitive and behavioral sequelae, thereby acquainting us with the role of the frontal cortex in higher-order actions such as reasoning, behavior and social cognition. In those years, while neuropsychiatry was in its infancy, Gage's extraordinary story served as one of the first pillars of evidence that the frontal lobe is involved in personality, which helped solidify his remarkable legacy in world medical history.

Attributions

Adapted from Phineas Gage’s Great Legacy by Vieira Teles Filho, Ricardo. Licensed CC BY 4.0 .

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An injury with an improbable outcome that occurred to a to a railway foreman on 13 September 1848 had an influence on the science of localisation of brain function. Phineas Gage was the foreman of a railway construction crew working just outside Cavendish, Vermont. He was the company's most capable foreman with a well balanced mind and shrewd business sense.

Gage was tamping an explosion charge. A tamping iron is a crowbar-like tool used to compact an explosive charge into the bottom of a borehole. The tamping iron used by Gage was 43 inches in length, 1.25 inches in diameter at one end, tapering over a distance of 12 inches to a diameter of 0.25 inches at the other end, and weighing about 13 pounds.Tamping involves packing of a charge into as small a space as possible at the point chosen for the explosion. An accidental explosion of the charge Phineas Gage …

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Research Article

Mapping Connectivity Damage in the Case of Phineas Gage

* E-mail: [email protected]

Affiliation Laboratory of Neuro Imaging (LONI), Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America

Affiliation Surgical Planning Laboratory, Department of Radiology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America

John Darrell Van Horn,
Andrei Irimia,
Carinna M. Torgerson,
Micah C. Chambers,
Ron Kikinis,
Arthur W. Toga

Published: May 16, 2012
https://doi.org/10.1371/journal.pone.0037454
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Citation: Van Horn JD, Irimia A, Torgerson CM, Chambers MC, Kikinis R, Toga AW (2012) Mapping Connectivity Damage in the Case of Phineas Gage. PLoS ONE 7(5): e37454. https://doi.org/10.1371/journal.pone.0037454

Editor: Olaf Sporns, Indiana University, United States of America

Received: August 3, 2011; Accepted: April 23, 2012; Published: May 16, 2012

Copyright: © 2012 Van Horn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing interests: The authors have declared that no competing interests exist.

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https://doi.org/10.1371/journal.pone.0037454.g003

https://doi.org/10.1371/journal.pone.0037454.g004

https://doi.org/10.1371/journal.pone.0037454.t005

Tables 6 and 7 provide details on the regional coding used for brain parcellation which were subjected to estimation of the effects of the tamping iron, lesion simulation modeling, and which encode the text on the outer-most rings of Figs. 2 and 3 . Differences in measures of network connectivity due to the rod's passage were apparent in terms of network integration, segregation, but not small worldness as compared to the unlesioned, healthy network. Specifically, when removing those cortical areas and fiber pathways intersected by the iron, characteristic path length was found to be significantly decreased in Gage compared to the intact network ( p ≤0.0001), mean local efficiency was decreased ( p ≤0.0001), while small worldness showed no statistical difference ( p ≤0.9467, ns). Regionally-specific network theoretical metrics in the affected regions and those to which they connect were also affected (see Fig. 5A ). This suggests that, not surprisingly, with significant loss of WM connectivity between left frontal regions and the rest of the brain, the surviving network of brain was likely to have been heavily impaired and its functions considerably compromised.

https://doi.org/10.1371/journal.pone.0037454.g005

https://doi.org/10.1371/journal.pone.0037454.t006

https://doi.org/10.1371/journal.pone.0037454.t007

Trajectory of the Tamping Iron

Alterations of Network Connectivity Due to the Tamping Iron

Implications for Gage's Reported Behavioral Changes

Historical Implications of Gage's WM Damage

Limitations of our Study

Conclusions

Ethics Statement

Medical Imaging of the Gage Skull

Documented Extent of Neurological Damage

Skull CT Data Processing

The LONI Pipeline Workflow Environment

Measurements of the Skull

Measurements of the Tamping Iron

The Trajectory of the Tamping Iron

Determining the Trajectory of the Tamping Iron

Normal Subjects

Segmentation and Parcellation

Connectogram Design

Color Coding Schemes

Each cortical lobe was assigned a unique color scheme: black to red to yellow (Fro), charlotte to turquoise to forest green (Ins), primrose to lavender rose (Lim), pink to lavender to rosebud cherry (Tem), lime to forest green (Par), and lilac to indigo (Occ). Each structure was assigned its unique RGB color based on esthetic considerations; e.g. subcortical structures were colored light gray to black. Color scheme choice and assignment to each lobe were made by taking into account the arrangement and adjacency of lobes on the cortical surface, with the goal of avoiding any two adjacent lobes from having overlapping or similar color schemes which were too similar. The individual colors of the scheme associated with any particular lobe were assigned to every parcellation within that lobe in such a way as to create a distinct contrast when displayed on cortical surfaces ( Fig. S2 ) or on the connectogram graphics ( Figs. 2 and 3 ). The particular regional color mappings employed in this article can be considered arbitrary and are not intended to convey any universal or standard regional color scheme, per se .

Representation of Cortical Metrics

Connectivity Calculation

Connectivity Representation

Representation of Connectivity Affected by Pathology

Calculation of Pathology Effects upon GM/WM Volumetrics

Average Percentages of Brain Regions Intersected by the Rod

Network Analysis

Equivalent Lesion Simulation and Comparison

Supporting Information

https://doi.org/10.1371/journal.pone.0037454.s001

https://doi.org/10.1371/journal.pone.0037454.s002

https://doi.org/10.1371/journal.pone.0037454.s003

https://doi.org/10.1371/journal.pone.0037454.s004

https://doi.org/10.1371/journal.pone.0037454.s005

https://doi.org/10.1371/journal.pone.0037454.s006

https://doi.org/10.1371/journal.pone.0037454.s007

Acknowledgments

Author Contributions

1. Rosen B, Wedeen V, Van Horn JD, Fischl B, Buckner R, et al. (2010) The Human Connectome Project. Organization for Human Brain Mapping Annual Meeting. Barcelona, Spain.
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3. Macmillan M (2000) An Odd Kind of Fame: Stories of Phineas Gage. Boston: MIT Press. 576 p.
4. Damasio AR (1995) 336 p. Descartes' Error: Harper Perennial.
83. Sporns O (2011) Networks of the Brain. Cambridge, MA: MIT Press.

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Phineas Gage & the Social Brain Field Trip

Students in a course on the brain and social interaction visit the museum housing phineas gage’s skull and discuss it as a case study of the effects of brain injury on social behavior..

To introduce students to the relationship between brain damage and social behavior.
To engage students in the material through first-hand exposure to a famous case in neuroscience history.

Class: PSY1559: The Social Brain

Introduction/Background:

This activity uses a specific case study of focal brain injury that is particularly relevant to the course to launch a broader discussion of what neuroscientists and psychologists can learn from patients with brain damage and what limitations should be kept in mind. Traveling to the museum to see the damage to Gage's skull in person provides the students with a hands-on experience that is more impactful than simply viewing photographs in textbooks and Powerpoints.

Before Class:

Students were assigned two readings to complete prior to class, listed under materials.
Students were given instructions and details via email and also verbally in class several weeks before the field trip was to occur about where and when to meet to take the bus to the museum.

During Class

Students visited the Warren Anatomical museum at Harvard Medical School.
After viewing the exhibit containing Phineas Gage's skull, tamping iron, and other associated items, they engaged in a discussion about Gage's case - what it teaches about social behavior, why it remains of interest to psychologists and neuroscientists, and more broadly how brain damage can help inform brain function.
Students were asked to specifically relate course readings to Gage's case and speak to generalizations and limitations of lesion studies (studies of patients with brain damage).

“Phineas Gage, neuroscience’s most famous patient,” Slate - link

Beer, Jennifer S., et al. "Orbitofrontal cortex and social behavior: integrating self-monitoring and emotion-cognition interactions." Cognitive Neuroscience, Journal of 18.6 (2006): 871-879.

Questions for discussion (attached)

Instructor Comments:

As Powers writes, “This activity is particularly well-suited to smaller classes, to ensure feasibility as well as sufficient in-depth discussion. It is not that a discussion of these issues can't take place in a classroom on campus, but I think that adding a tangible, hands-on dimension to this topic will ground the students' understanding of the issues, increase enthusiasm about the material and enhance the quality of discussion and lessons learned.”

Submitted by Katherine Powers, Harvard College Fellow, Department of Psychology

17 KB

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COMMENTS

What Happened to Phineas Gage?
The case of Phineas Gage has been of huge interest in the field of psychology and is a largely speculated phenomenon. Gage suffered a severe brain injury from an iron rod penetrating his skull, which he miraculously survived. After the accident, Gage's personality was said to have changed as a result of the damage to the frontal lobe of his brain.
Phineas Gage
Strengths of the study. Weaknesses of the study. You may have already heard of Phineas Gage, such is his infamous history with psychology. He was working on a railway line in the USA when there was an explosion, which resulted in an iron rod being fired through his head. He survived the accident even though there were serious injuries to his ...
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At his hotel, Gage waited in a chair on the porch and chatted with passersby—who were, uh, startled to see a volcano of bone jutting out of his scalp. Thus began perhaps the most famous case in medical history. Every neuroscience textbook in existence has a section on Phineas Gage. Incredibly, though, nearly every textbook gets the story wrong.
Phineas Gage: Biography, Brain Injury, and Influence
Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book." Phineas Gage suffered a terrible accident that made him one of the most famous cases of traumatic brain injury. Learn Gage's story and its impact on psychology.
Phineas Gage's great legacy
The case of Phineas Gage is an integral part of medical folklore. His accident still causes astonishment and curiosity and can be considered as the case that most influenced and contributed to the nineteenth century's neuropsychiatric discussion on the mind-brain relationship and brain topography. It was perhaps the first case to suggest the ...
Phineas Gage: A Neuropsychological Perspective of a Historical Case Study
Abstract. The case of Phineas Gage is one of the most frequently cited cases from 19th century medical literature and represents the first of a series of famous cases involving the brain and behavior.
Phineas Gage: A Neuropsychological Perspective of a Historical Case Study
Horrible Accident—As Phineas P. Gage, a foreman on the railroad in Cavendish, was yesterday engaged in tamkin [sic] for a blast, the powder exploded, carrying an iron instrument through his head an inch and a fourth in circumference, and three feet and eight inches in length, which he was using at the time.
Lessons of the brain: The Phineas Gage story
Imagine the modern-day reaction to a news story about a man surviving a three-foot, 7-inch, 13½-pound iron bar being blown through his skull — taking a chunk of his brain with it. Then imagine that this happened in 1848, long before modern medicine and neuroscience. That was the case of Phineas Gage. Whether the Vermont construction foreman ...
PDF The case of Phineas Gage
The case of Phineas Gage The role of the brain in social cognition was first documented by John Harlow, a physician who attended Phineas Gage, a railroad construction ... Like the study of language, the study of these functions depends on modern methods for investigating brain function in humans: fMRI, ERP, as ...
PDF The Curious Case of Phineas Gage
In 1848, Phineas Gage, a young railroad foreman in Vermont was involved in a freak and terrible accident that caused a railroad tamping rod to shoot up, at very high speed, under his left eye and exit through the top of his head. Gage survived the accident, and apparently never even lost consciousness, but what happened in the weeks and months ...
Mapping Connectivity Damage in the Case of Phineas Gage
The case of Phineas Gage is among the most famous and infamous in the history of brain science. The interpretations of his incredible injury and attempts to characterize it have been ongoing since soon after it occurred. ... Limitations of our Study. We have worked to provide a detailed, accurate, and comprehensive picture of the extent of ...
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The study of individual patients is an essential component of the neuropsychiatric literature, a springboard for paradigm shifts in research, and a cornerstone of physician training in neurology and psychiatry. This article revisits six landmark case reports that challenged the field of medicine to expand its understanding of pathophysiology ...
1.3: The Case of Phineas Gage- Connecting Brain to Behavior
The case of Phineas Gage is worthy of expanded coverage as his tragic accident establishes a clear connection between the brain and who we are. Gage, a 25-year-old man, was employed in railroad construction at the time of the accident. As the company's most capable employee, with a well-balanced mind and a sense of leadership, he was directing ...
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6 March 2011. A metre-long iron rod travelled through Phineas Gage's head, emerging out of the top of his skull. By Claudia Hammond & Dave Lee. BBC World Service. "Phineas Gage had a hole in his ...
Phineas Gage: The brain and the behavior
Abstract No. 4. Phineas Gage has long occupied a privileged position in the history of science. Few isolated cases have been as influential, in the neurological and neuroscientific thinking, and yet the documentation on which conclusions and interpretations rest are remarkably incomplete [1], [2]. We do have a number of sure facts:
Phineas Gage and the science of brain localisation
An injury with an improbable outcome that occurred to a to a railway foreman on 13 September 1848 had an influence on the science of localisation of brain function. Phineas Gage was the foreman of a railway construction crew working just outside Cavendish, Vermont. He was the company's most capable foreman with a well balanced mind and shrewd business sense. Gage was tamping an explosion ...
Phineas Gage: A case for all reasons.
[re-examine the case of 25-yr-old Phineas P. Gage,] a medical curiosity and a famous victim of brain injury, possibly the most famous / present as full an account of his case as possible and outline the main uses to which it has been put before concluding that it supports very few neuropsychological generalizations Gage's [work] accident / Gage pre-accident / Gage in the immediate post ...
PDF The curious case of Phineas Gage
Additional notes. There is potential for comparison with the case of Gabby Giffords considered on the next textbook spread. Answers. 1. The details of Phineas Gage's accident and subsequent behaviour could be considered to be. a case study. Find a suitable definition of a case study. From the textbook page 64: An in depth investigation ...
PDF The story of Phineas Gage
Phineas Gage, the foreman of a group of railway construction workers, had packed explosives with a tamping iron to blast apart a rock lying in the path of the rail-road. He dropped the iron, which then struck the rock. There was an explosion and the 3-foot-7-inches-long iron was driven completely through Gage's left frontal lobe and landed ...
E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury
Evidence before this study. The historical case of Phineas Gage (1848) is an integral part of medical folklore, illustrating the resilience of the human brain and the involvement of the frontal lobes in problem solving, spontaneity, memory, initiation, judgement, impulse control, and social and sexual behavior.
PDF Chapter 2: Biopsychology The curious case of Phineas Gage Localisation
Answer the questions that follow in preparation for a class discussion. 1. The details of Phineas Gage's accident and subsequent behaviour could be considered to be a case study. Find a suitable definition of a case study. 2. The 'reconstruction' reminds us of one of the weaknesses of case studies - that we can only assume that the ...
Mapping Connectivity Damage in the Case of Phineas Gage
The case of Phineas Gage is among the most famous and infamous in the history of brain science. The interpretations of his incredible injury and attempts to characterize it have been ongoing since soon after it occurred. ... Limitations of our Study. We have worked to provide a detailed, accurate, and comprehensive picture of the extent of ...
Phineas Gage & the Social Brain Field Trip
Students in a course on the brain and social interaction visit the museum housing Phineas Gage's skull and discuss it as a case study of the effects of brain injury on social behavior. Goals: To introduce students to the relationship between brain damage and social behavior. To engage students in the material through first-hand exposure to a ...

Phineas Gage: His Accident and Impact on Psychology

Key Takeaways

What happened to Phineas Gage?

How Did Phineas Gage’s Personality Change?

Accuracy of Sources

Severity of Gage’s Brain Damage

What Happened to Phineas Gage After the Brain Damage?

How did Phineas Gage die?

Why Is Phineas Gage Important to Psychology?

Further Reading

If a person suffers from a traumatic brain injury in the prefrontal cortex, similar to that of Phineas Gage, what changes might occur?

Phineas Gage

Strengths of the study

Weaknesses of the study

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Phineas Gage: His Accident and Impact on Psychology

What Happened to Phineas Gage After the Brain Damage?

At a Glance

Phineas Gage's Accident

The Recovery Process

Theories About Gage's Survival and Recovery

How Did Phineas Gage's Personality Change?

Severity of Gage's Brain Damage

Why Is Phineas Gage Important to Psychology?

Bottom Line

41 Phineas Gage: A Neuropsychological Perspective of a Historical Case Study

Introduction

The Accident Site

The Accident

Eyewitness Accounts

First Responder

The Treating Physician

Harlow’s Physical Medicine and Rehabilitation

Status Post Discharge

Harlow’s Reexamination

Dr. Henry Bigelow: A Second Opinion

Gage’s Change in Mental Status: Frontal Cortical Injury

Long-Term Recovery

Gage’s Final Resting Place

Why Study Gage?

Historical Importance

Clinical Relevance

Most Reiterations Contain Errors

Uniqueness and Interest

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