ys

The dopamine pathways in schizophrenia

In schizophrenia there is an increase in dopamine transmission between the substantia nigra to the
caudate nucleus-putamen (neostriatum) compared with normal. While in the other major
dopaminergic pathways to the mesolimbic forebrain and the tubero-infundibular system
dopamine transmission is reduced. The dopamine hypothesis of schizophrenia proposes that
increased levels of dopamine or dopamine receptors in the dorsal and or ventral striatum underlie
the disorder.

The glutamate pathways in a brain affected by schizophrenia

In the normal brain the prominent glutamatergic pathways are: the cortico-cocortical pathways; the
pathways between the thalamus and the cortex; and the extrapyramidal pathway (the projections
between the cortex and striatum). Other glutamate projections exist between the cortex, substantia
nigra, subthalmic nucleus and pallidum. The glutamatergic pathways are hypoactive in the brains
people diagnosed with schizophrenia and this is thought to cause the confusion and psychosis
associated with the disorder.

The serotonergic pathway showing the effects of schizophrenia

The two key serotonergic pathways in schizophrenia are the projections from the dorsal raphe nuclei
into the substantia nigra and the projections from the rostral raphe nuclei ascending into the cerebral
cortex, limbic regions and basal ganglia. The up-regulation of these pathways leads to hypofunction
of the dopaminergic system, and this effect may be responsible for the negative symptoms of
schizophrenia. The serotonergic nuclei in the brainstem that give rise to descending serotonergic
axons remain unaffected in schizophrenia.

Phineas Gage

Sources: http://en.wikipedia.org/wiki/Phineas_Gage
http://neurophilosophy.wordpress.com/2006/12/04/the-incredible-case-of-phineas-gage/
Phineas Gage (1823-1860) is one of the earliest documented cases of severe brain injury. Gage is the
index case of an individual who suffered major personality changes after brain trauma, at a period in
history where very little was known about how the brain worked and how the brain repaired itself
after a traumatic event.
Gage was foreman of a crew of railroad construction workers who were excavating rocks to make
way for the railroad track. This involved drilling holes deep into the boulders and filling them with
dynamite. A fuse was then inserted, and the entrance to the hole plugged with sand, so that the force
of the explosion would be directed into the boulder. This was done with a crow bar-like tool called a
tamping iron.
On 13th September, 1848, 25-year-old Gage and his crew were working on the Rutland and
Burlington Railroad near Cavendish in Vermont. Gage was preparing for an explosion by compacting
a bore with explosive powder using a tamping iron. While he was doing this, a spark from the
tamping iron ignited the powder, causing the iron to be propelled at high speed straight through
Gage's skull. It entered under the left cheek bone and exited through the top of the head, and was
later recovered some 30 yards from the site of the accident.

Whether or not Gage lost consciousness is not known, but, remarkably, he was conscious and able to
walk within minutes of the accident. He was then seated in an oxcart, on which he was transported
three-quarters of a mile to the boarding house where he was staying. Here, he was attended to by
Harlow, the local physician. At the boarding house, Harlow cleaned Gage's wounds by removing
small fragments of bone, and replaced some of the larger skull fragments that remained attached but
had been displaced by the tamping iron. He then closed the larger wound at the top of Gage's head
with adhesive straps, and covered the opening with a wet compress. Gage's wounds were not treated
surgically, but were instead left open to drain into the dressings.
Within a few days of his accident, one of Gage's exposed brain became infected with a "fungus", and
he lapsed into a semi-comatose state. His family prepared a coffin for him, but Gage recovered. Two
weeks after the accident, Harlow released 8 fluid ounces of pus from an abscess under Gage's scalp,
which would otherwise have leaked into the brain, with fatal consequences. By 1st January 1849,
Gage was leading an apparently normal life.
Gage did, according to Harlow, retain "full possession of his reason" after the accident, but his wife
and other people close to him soon began to notice dramatic changes in his personality. It wasn't until
1868 that Harlow documented the "mental manifestations" of Gage's brain injuries, in a report
published in the Bulletin of the Massachusetts Medical Society:

One of three figures from Harlow's 1868 paper. The legend reads:
Front and lateral view of the cranium, representing the direction in which the iron traversed its cavity; the present
appearance of the line of fracture, and also the large anterior fragment of the frontal bone, which was entirely detached,
replaced and partially re-united.

[ 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 his
place again. 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 of
advice when it conflicts with his desires, at times pertinaciously obstinent, 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. In this regard, his mind was radically
changed, so decidedly that his friends and acquaintances said he was "no longer Gage."]
Thus, the damage to Gage's frontal cortex had resulted in a complete loss of social inhibitions, which
often led to inappropriate behaviour. In effect, the tamping iron had performed a frontal lobotomy on
Gage, but the exact nature of the damage incurred to his brain has been a subject of debate ever since
the accident occurred. This is because the damage can only be inferred from the path of the tamping
iron through Gage's skull, which in turn can only be inferred from the damage to the skull.
Gage's skull was damaged in three places: there is a small wound under the left zygomatic arch
(cheek bone) where the tamping iron entered; another is located in the orbital bone in the base of the
skull behind the orbit of the eye; and the third, and largest, wound is in the top of the skull, where the
tamping iron exited. The exit wound was enormous, and never healed. It can be seen today in Gage's
as an irregularly-shaped triangular hole, about 2 inches wide and 4 inches in circumference, and
another, nearly 3 inches in circumference. These are separated by one of the flaps of skull that was
replaced by Harlow upon arriving at Gage's boarding house. Because the circumference of the wound
in the frontal bone is much larger than the maximum diameter of the tamping iron, it is difficult to
determine precisely the trajectory of the iron and where it exited Gage's skull.

Gage's case confirmed findings that damage to the prefrontal cortex could result in personality
changes while leaving other neurological functions intact. Gage's case is one of the very first which
provides evidence that the frontal cortex is involved in personality. Today, the role of frontal cortex in
social cognition and executive function is relatively well established; however, this area of research
is yet to blossom, and neuroscientists know little more about the relationship between the mind and
the brain than did the early neurologists of the 19th century.
So, what of Phineas Gage himself? Unable to return to his previous job as a foreman after his
accident, Gage is said to have travelled around New England, and even to Europe, with his tamping
iron trying to earn money. It is also said that he even displayed himself as a curiosity at Barnum's
Circus in New York. However, the story of Phineas Gage is as much folklore as it is fact. Not only
the exact nature of the neurological damage Gage sustained, but also the details of his life after the
accident, are disputed to this day.
In 1867, Gage's body was exhumed from its burial place in San Francisco's Lone Mountain
Cemetery. Gage's brother-in-law took the skull and the tamping iron to Dr. Harlow, who was then
living in Woburn, Massachusetts. They are now housed in the Warren Anatomical Museum at
Harvard University School of Medicine.

Gage was no longer Gage

he first story that appeared about Gage contained a mistake. The day after his

accident, a local newspaper misstated the diameter of the rod. A small error, but an omen of
much worse to come.
Psychologist and historian Malcolm Macmillan, currently at the University of Melbourne, has
been chronicling mistakes about Gage for 40 years. He has had a peripatetic career: Among
other topics, he has studied disabled children, Scientology, hypnosis, and fascism. In the
1970s, he got interested in Gage and decided to track down original material about the
case. He turned up alarmingly little, and realized just how rickety the evidence was for most
of the science about Gage.
Because Gage could still walk, talk, see, and hear, Bigelow concluded that his brain must be
fine.
Macmillan has been sifting fact from fiction ever since, and he eventually published a
scholarly book about Gages story and its afterlife, An Odd Kind of Fame. Although slowed
by a faulty hip replacementhe has trouble reaching books on the bottom shelves at
libraries nowMacmillan continues to fight for Gages reputation, and he has gotten so
involved with his subject that he now refers to him, familiarly, as Phineas. Above all,
Macmillan stresses the mismatch between what we actually know about Gage and the
popular understanding of him: Despite there being no more than a couple hundred words
attesting to how he changed, he came to dominate thinking about the function of the frontal
lobes.
The most important firsthand information comes from John Harlow, a self-described
obscure country physician who was the second doctor to reach Gage the day of the
accident, arriving around 6 p.m. Harlow watched Gage lumber upstairs to his hotel room
and lie down on the bedwhich pretty much ruined the linens, since Gages body was one
big bloody mess. As for what happened next, readers with queasy stomachs should
probably skip to the next paragraph. Harlow shaved Gages scalp and peeled off the dried
blood and brains. He then extracted skull fragments from the wound by sticking his fingers
in from both ends, Chinese-finger-trap-style. Throughout this all, Gage was retching every
20 minutes, because blood and greasy bits of brain reportedly kept slipping down the back

of his throat and gagging him. Incredibly, Gage never got ruffled, remaining conscious and
rational throughout. He even claimed hed be back blasting rocks in two days.

American physician John M. Harlow.

Photo courtesy Creative Commons

The bleeding stopped around 11 p.m., and Gage rested that night. The next morning his
head was heavily bandaged and his left eyeball was still protruding a good half-inch, but
Harlow allowed him visitors, and Gage recognized his mother and uncle, a good sign.
Within a few days, however, his health deteriorated. His face puffed up, his brain swelled,
and he started raving, at one point demanding that someone find his pants so he could go
outside. His brain developed a fungal infection and he lapsed into a coma. A local cabinetmaker measured him for a coffin.
Fourteen days into the crisis, Harlow performed emergency surgery, puncturing the tissue
inside Gages nose to drain the wound. Things were touch-and-go for weeks, and Gage did
lose sight in his left eye, which remained sewn shut the rest of his life. But he eventually
stabilized, and in late November he returned home to Lebanon, New Hampshirealong
with his tamping iron, which he started carrying around with him everywhere. In his case
report, Harlow modestly downplayed his role in the recovery: I dressed him, he wrote,
God healed him.
During his convalescence, stories about Gage started circulating in newspapers, with
varying degrees of accuracy. Most gave Gage the tabloid treatment, emphasizing the sheer
improbability of his survival. Doctors gabbed about the case, tooalbeit with a dose of

skepticism. One physician dismissed Gage as a Yankee invention, and Harlow said that
others, like St. Thomas with Jesus, refused to believe that the man had risen until they had
thrust their fingers into the hole of his head.
Dr. Henry Bigelow brought Gage to Harvard Medical School for a formal evaluation in 1849.
Although Bigelow treated Gage like a curiosityhe once presented Gage at a meeting
along with a stalagmite remarkable for its singular resemblance to a petrified penisthe
visit resulted in the only other detailed, firsthand account of Gage and his accident besides
Harlows. Surprisingly, Bigelows report pronounced Gage quite recovered in his faculties of
body and mind. However, as was common in neurological exams then, Bigelow probably
only tested Gage for sensory and motor deficits. And because Gage could still walk, talk,
see, and hear, Bigelow concluded that his brain must be fine.

Daguerreotype of Henry Jacob

Bigelow.
Photo courtesy Harvard Art Museum/Fogg Museum

Bigelows assessment meshed well with the medical consensus at the time, which held that
the frontal lobes didnt do muchin part because people could suffer grave injuries to them
and walk away. Scientists now know that parts of the frontal lobes contribute to nearly every

activity inside the brain. The forefront of the lobes, called the prefrontal area, plays an
especially important role in impulse control and planning.
But even today scientists have only a vague idea of how the prefrontal lobes exercise that
control. And victims of prefrontal injuries can still pass most neurological exams with flying
colors. Pretty much anything you can measure in the labmemory, language, motor skills,
reasoning, intelligenceseems intact in these people. Its only outside the lab that problems
emerge. In particular, personalities might change, and people with prefrontal damage often
betray a lack of ambition, foresight, empathy, and other ineffable traits. These arent the kind
of deficits a stranger would notice in a short conversation. But family and friends are acutely
aware that something is off.
Frustratingly, Harlow limited his discussion of Gages mental status to a few hundred words,
but he does make it clear that Gage changedsomehow. Although resolute before the
accident, Harlow says Gage was now capricious, and no sooner made a plan than dropped
it for another scheme. Although deferential to peoples wishes before, Gage now chafed at
any restraint on his desires. Although a smart, shrewd businessman before, Gage now
lacked money sense. And although courteous and reverent before, Gage was now fitful
[and] irreverent, indulging at times in the grossest profanity. Harlow summed up Gages
personality changes by saying, the equilibrium ... between his intellectual faculties and his
animal propensities seems to have been destroyed. More pithily, friends said that Gage
was no longer Gage.
As a result of this change, the railroad refused to reinstate Gage as foreman. He began
traveling around New England instead, displaying himself and his tamping iron for money.
This included a stint in P.T. Barnums museum in New Yorknot Barnums traveling circus,
as some sources claim. For an extra dime, skeptical viewers could part Gages hair and
see his brain ... pulsating beneath his scalp. Gage finally found steady work driving a horse
coach in New Hampshire.
Beyond that sketch of his activities, theres no record of what Gage did in the months after
the accidentand we know even less about what his conduct was like. Harlows case report
fails to include any sort of timeline explaining when Gages psychological symptoms
emerged and whether any of them got better or worse over time. Even the specific details of
Gages behavior seem, on a closer reading, ambiguous, even cryptic. For instance, Harlow
mentions Gages sudden animal propensities and, later, animal passions. Sounds
impressive, but what does that mean? An excessive appetite, strong sexual urges, howling
at the moon? Harlow says that Gage cursed at times, but how often is that? And was this a
saucy hell or damn here and there, or something more dastardly? Harlow notes that
Gage started telling his nieces and nephews wild stories about his supposed adventures.

Was he confabulating here, a symptom of frontal lobe damage, or simply indulging a love of
tall tales? Even the conclusion that Gage was no longer Gage could mean almost
anything.

PHINEAS GAGE (1823-1860) is one of the earliest documented cases of severe brain injury. Gage is
the index case of an individual who suffered major personality changes after brain trauma. As such,
he is a legend in the annals of neurology, which is largely based on the study of brain-damaged
patients.
Gage was foreman of a crew of railroad construction workers who were excavating rocks to make way
for the railroad track. This involved drilling holes deep into the rock and filling them with dynamite.
A fuse was then inserted, and the entrance to the hole plugged with sand, so that the force of the
explosion would be directed into the boulder. This was done with a crow bar-like tool called a
tamping iron.
On 13th September, 1848, 25-year-old Gage and his crew were working on the Rutland and
Burlington Railroad near Cavendish in Vermont. Gage was preparing for an explosion by compacting
a bore with explosive powder using a tamping iron. While he was doing this, a spark from the
tamping iron ignited the powder, causing the iron to be propelled at high speed straight through his
skull. It entered under the left cheek bone and exited through the top of the head, and was later
recovered some 30 yards from the site of the accident.

John Martin Harlow, the doctor who attended to him, later noted that the tamping iron was found
several rods [1 rod= 5.02m] behind him, where it was afterward picked up by his men smeared with
blood and brain. The tamping iron was 3 ft. 8 inches in length and 1.25 inches in diameter at one
end, not 1.25 inches in circumference, as reported in the newspaper report on the left. It tapered at
one end, over a distance of about 1 ft., to a blunt end 0.25 inches in diameter, and weighed more than
6 kg.
Whether or not Gage lost consciousness is not known, but, remarkably, he was conscious and able to
walk within minutes of the accident. He was then seated in an oxcart, on which he was transported
three-quarters of a mile to the boarding house where he was staying. Here, he was attended to by
Harlow, the local physician. At the boarding house, Harlow cleaned Gages wounds by removing
small fragments of bone, and replaced some of the larger skull fragments that remained attached but
had been displaced by the tamping iron. He then closed the larger wound at the top of Gauges head
with adhesive straps, and covered the opening with a wet compress. Gages wounds were not treated
surgically, but were instead left open to drain into the dressings.
Within a few days of his accident, Gages exposed brain became infected with a fungus, and he
lapsed into a semi-comatose state. His family prepared a coffin for him, but Gage recovered. Two
weeks after the accident, Harlow released 8 fluid ounces of pus from an abscess under Gages scalp,
which would otherwise have leaked into the brain, with fatal consequences. By 1st January 1849,
Gage was leading an apparently normal life.
Harlows case report of Gages injuries appeared as a letter to the editor of the Boston Medical and
Surgical Journal. The report of the hitherto unparalleled case contains few neurological details,
and was at first met with skepticism, because it was thought that no-one could survive such an
extreme injury. Harlow describes Gages injury as follows:
[The tamping iron] entered the cranium, passing through the anterior left lobe of the cerebrum, and
made its exit in the medial line, at the junction of the coronal and sagittal sutures, lacerating the
longitudinal sinus, fracturing the parietal and frontal bones extensively, breaking up considerable
portions of the brain, and protruding the globe of the left eye from its socket, by nearly half its diameter.

Harlow goes on to describe how, while examining Gage, he determined that no bone fragments
remained inside the skull:
in searching to ascertain if there were other foreign bodies there, I passed in the index finger its whole
length, without the least resistance, in the direction of the sound [of the hemorrhaging?] in the cheek,
which received the other finger in like manner.

A second report was published in 1850 by Henry J. Bigelow, a professor of surgery at Harvard
University. Bigelow emphasised Gages lack of symptoms, and reported that Gage was quite
recovered in faculties of body and mind. Because of the disbelief with which Harlows 1848 report
was met, it was, for the next 20 years, Bigelows account that came to be generally accepted by the
medical community.
Gage did, according to Harlow, retain full possession of his reason after the accident, but his wife
and other people close to him soon began to notice dramatic changes in his personality. It wasnt
until 1868 that Harlow documented the mental manifestations of Gages brain injuries, in a report
published in the Bulletin of the Massachusetts Medical Society:
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 his place again.
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 of advice when it conflicts
with his desires, at times pertinaciously obstinent, 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. In this regard, his mind was radically changed, so decidedly that his friends
and acquaintances said he was no longer Gage.

On the right is one of three figures from Harlows 1868 paper. The legend reads:
Front and lateral view of the cranium, representing the direction in which the iron traversed its cavity;
the present appearance of the line of fracture, and also the large anterior fragment of the frontal bone,
which was entirely detached, replaced and partially re-united.

Thus, the damage to Gages frontal cortex had resulted in a complete loss of social inhibitions, which
often led to inappropriate behaviour. In effect, the tamping iron had performed a frontal lobotomy

on Gage, but the exact nature of the damage incurred to his brain has been a subject of debate ever
since the accident occurred. This is because the damage can only be inferred from the path of the
tamping iron through Gages skull, which in turn can only be inferred from the damage to the skull.
Gages skull was damaged in three places: there is a small wound under the left zygomatic arch
(cheek bone) where the tamping iron entered; another is located in the orbital bone in the base of the
skull behind the orbit of the eye; and the third, and largest, wound is in the top of the skull, where
the tamping iron exited. The exit wound was enormous, and never healed. It can be seen today in
Gages as an irregularly-shaped triangular hole, about 2 inches wide and 4 inches in circumference,
and another, nearly 3 inches in circumference. These are separated by one of the flaps of skull that
was replaced by Harlow upon arriving at Gages boarding house. Because the circumference of the
wound in the frontal bone is much larger than the maximum diameter of the tamping iron, it is
difficult to determine precisely the trajectory of the iron and where it exited Gages skull.
In 1994, Hannah Damasio and her colleagues at the University of Iowa used neuroimaging
techniques to reconstruct Gages skull. The conclusion of this study was that Gage incurred damage
to both the left and right prefrontal cortices. But according to computer-generated three-dimensional
reconstructions of a thin slice computed tomography scan of Gages skull performed by Ratiu et
al (see image and film clip above), the damage to Gages brain was limited to the left hemisphere.
Nevertheless, the case of Phineas Gage made important contributions to early modern neurology.
The opposition to Harlows 1848 report was due in no small part to the popularity of phrenology at
that time. The publication of Harlows 1868 report of Gages personality changes was significant, as it
coincided with reports from other neurologists of the effects of specific lesions on behaviour.
This was a time when modern neuropsychology had begun to replace phrenology. In 1865, Paul
Broca (1824-1880) described the speech centre in the left hemisphere of right-handed people; that
brain region, in the inferior frontal gyrus, is now known as Brocas area. Also in the 1860s, John
Hughlings-Jackson (1835-1911) and David Ferrier carried out (1843-1928) physiological studies
which pointed to the localization of cerebral function.
Jackson had been the first to hypothesize that psychopathological conditions could be correlated to
brain damage. He also localized the auditory cortex and in 1864, confirmed Brocas findings that, in
right-handed people, speech was localized to a specific area of the left temporal lobe. Ferrier, an early
proponent of the localization of cerebral function, used Gages case as the highlight of his famous
Goulstonian lecture in 1878. In the same lecture, he also described experiments on monkeys, which
led him to the conclusion that:
There are certain regions in the cortex to which definite functions can be assigned; and that the
phenomena of cortical lesions will vary according to their seat and also to their characterremoval or

destructionof the antero-frontal lobes is not followed by any definite physiological resultsAnd yet,
notwithstanding this apparent absence of physiological symptoms, I could perceive a very decided
alteration in the animals character and behaviour, while it is difficult to state in precise terms the
nature of the changewhile not actually deprived of intelligence, they had lost, to all appearance, the
faculty of the attentive and intelligent observation [Regarding the trajectory of the tamping iron
through Gages brain]the absence of paralysis in this case is quite in harmony with the results of
experimental physiology.

Gages case, therefore, had confirmed Ferriers findings that damage to the prefrontal cortex could
result in personality changes while leaving other neurological functions intact. Gages case is one of
the very first which provides evidence that the frontal cortex is involved in personality. Today, the
role of frontal cortex in social cognition and executive function is relatively well established;
however, this area of research is yet to blossom, and neuroscientists know little more about the
relationship between the mind and the brain than did the early neurologists of the 19th century.
So, what of Phineas Gage himself? Unable to return to his previous job as a foreman after his
accident, Gage is said to have travelled around New England, and even to Europe, with his tamping
iron trying to earn money. It is also said that he even displayed himself as a curiosity at Barnums
Museum in New York. However, the story of Phineas Gage is as much folklore as it is fact. Not only
the exact nature of the neurological damage Gage sustained, but also the details of his life after the
accident, are disputed to this day.
It is known that, from 1851 until just before his death, Gage worked as a coach driver, first in a livery
stable at the Dartmouth Inn, in Hanover, New Hampshire, for about 18 months, and then in Chile for
some 7 years. At some point in 1859, with his health deteriorating, Gage went to live with his mother.
He died in San Francisco on 20th May, 1860, some 12 years after his accident, of complications
arising as a result of epileptic convulsions. An autopsy on Gages brain was not conducted.

In 1867, Gages body was exhumed from its burial place in San Franciscos Lone Mountain Cemetery.
Gages brother-in-law took the skull and the tamping iron to Dr. Harlow, who was then living in
Woburn, Massachusetts. They are now housed in the Warren Anatomical Museum at Harvard
University School of Medicine.

Boston Post newspaper report and Webster Wyman photo of skull and tamping iron reproduced with
permission from An Odd Kind of Fame: Stories of Phineas Gage, by Malcolm Macmillan. MIT Press,
2000.

Phineas Gage (18231860) was the victim of a terrible accident in 1848

His injuries helped scientists understand more about the brain and
human behaviour. Holly Story gets to grips with the grisly tale and its
place in the history of neuroscience.
Phineas Gage, whose story is also known as the American Crowbar Case,
was an unwitting and involuntary contributor to the history of neuroscience. In
1848, when he was just 25 years old, Gage sustained a terrible injury to his
brain. His miraculous survival, and the effects of the injury upon his character,
made Gage a curiosity to the public and an important case study for scientists
hoping to understand more about the brain.
In 1848 Gage was working as a foreman on the construction of the Rutland
and Burlington Railroad in Vermont, USA. Workers often used dynamite to
blast away rock and clear a path for the railway. On 13 September, Gage was
using a tamping iron (a long hollow cylinder of iron weighing more than 6 kilos)
to compact explosive powder into the rock ready for a blast. The iron rod hit
the rock, creating a spark that ignited the explosives. The rod was propelled
through Gages skull, entering through his left cheekbone and exiting through
the top of his head. It was later found some 30 yards away from
Gage, smeared with blood and brain.
Despite his horrific injury, within minutes Gage was sitting up in a cart,
conscious and recounting what had happened. He was taken back to his
lodgings, where he was attended by Dr John Harlow. The doctor cleaned and
dressed his wound, replacing fragments of the skull around the exit wound
and making sure there were no fragments lodged in the brain by feeling inside
Gages head with his finger. Despite Harlows efforts, the wound became
infected and Gage fell into a semi-comatose state. His family did not expect

him to survive: they even prepared his coffin. But Gage revived and later that
year was well enough to return to his parents home in New Hampshire.
In 1850 Henry J Bigelow, Professor of Surgery at Harvard University, reported
Gage to be quite recovered in faculties of body and mind.
It seems that physically, Gage made a good recovery, but his injury may have
had a permanent impact on his mental condition. Although accounts from the
time are sometimes conflicting and often unreliable, numerous sources report
that Gages character altered dramatically after his accident. In 1868 Harlow
wrote a report on the mental manifestations of Gages injuries. He described
Gage as fitful, irreverent, indulging at times in the grossest profanity
capricious and vacillating and being radically changed, so decidedly that his
friends and acquaintances said he was no longer Gage.
The damage to Gages frontal cortex caused by the iron rod seems to have
resulted in a loss of social inhibitions. The role of the frontal cortex in social
cognition and decision making is now well-recognised; in the 19th century,
however, neurologists were only just beginning to realise these connections.
Gages injuries provided some of the first evidence that the frontal cortex was
involved in personality and behaviour.
One of the pioneering researchers in this field at the time was David Ferrier, a
Scottish neurologist who performed extensive experimental research into
cerebral function. In a lecture to the Royal College of Physicians in 1878,
Ferrier observed that in his experiments on primates, damage to the frontal
cortices seemed to have no effect on the physical abilities of the animal but
brought about a very decided alteration in the animals character and
behavior. He used the experience of Phineas Gage as a case study to
support his claims.

The details of Gages life after his accident are unclear. It is known that he
worked as a coach driver for several years in New Hampshire and then in
Chile and that in 1859 his health deteriorated and he returned to New
Hampshire to live with his mother. He died in San Francisco in 1860 after
suffering seizures that resulted from his injury. His brain was not examined
after his death, but in 1867 his body was exhumed and his skull was sent to
Dr Harlow to be studied. It now resides, along with the tamping iron, at Warren
Anatomical Museum at the Harvard University School of Medicine.
Since then, scientists have made various attempts to use the skull to
reconstruct Gages injury and establish which areas of his brain were
damaged. Most recently, a team led by Jack Van Horn of UCLAs Laboratory
of Neuroimaging (part of the Human Connectome Project) created a new
digital model of the rods path. It suggested that the damage to Gages brain
was more extensive and severe than had previously been estimated: up to 4
per cent of the cerebral cortex and about 11 per cent of the total white matter
in the frontal lobe were destroyed.
The model also indicates that the accident damaged the connections between
the frontal cortex to the limbic system, which are involved in the regulation of
emotions. This would seem to support some of the contemporary reports of
Gages behaviour.
In the 19th century, Gages survival seemed miraculous. Fascination with his
plight encouraged scientific research into the brain, and the continuing
research into Gages condition is proof that this same curiosity is still alive
today.

RECOVERY AFTER SEVERE INJURY TO

THE HEAD.

MR. PRESIDENT AND FELLOWS OF THE MASSACHUSETTS MEDICAL SOCIETY:

I HAVE the pleasure of being able to present to you, to-day, the history and sequel of a case of severe
injury of the head, followed by recovery, which, so far as I know, remains without parallel in the
annals of surgery. The case occurred nearly twenty years ago, in an obscure country town
(Cavendish, Vt.), was attended and reported by an obscure country physician, and was received by
the Metropolitan Doctors with several grains of caution, insomuch that many utterly refused to
believe that the man had risen, until they had thrust their fingers into the hole of his head, and even
then they required of the Country Doctor attested statements, from clergymen and lawyers, before
they could or would believemany eminent surgeons regarding such an occurrence as a
physiological impossibility; the appearances presented by the subject being variously explained
away.
It is due to science, that a case so grave, and succeeded by such remarkable results, should not be
lost sight of; that its subsequent history, termination, and pathological evidences in detail, should
have a permanent record. My desire to lay before the profession the sequel of this case, has not
permitted me to remain altogether oblivious as to the whereabouts of my patient, and after tracing
him in his wanderings over the greater part of this continent, I am able to present to you indubitable
evidence that my report of the case, in the Boston Medical and Surgical Journal, was no fiction. You
will find the report in Vol. 39, No. 20, page 389, of the Journal; also a subsequent report, with
comments, by Prof. Henry J. Bigelow, in the American Journal of the Medical Sciences for July,
1850.[1]
The accident occurred in Cavendish, Vt., on the line of the Rutland & Burlington Railroad, at that
time being built, on the 13th of September, 1848, and was occasioned by the premature explosion of
a blast, when this iron, known to blasters as a tamping iron, and which I now show you, was shot
through the face and head.
The subject of it was Phin. P. Gage, a perfectly healthy, strong and active young man, twenty-five
years of age, nervobilious temperament, five feet six inches in height, average weight one hundred
and fifty pounds, possessing an iron will as well as an iron frame; muscular system unusually well
developedhaving had scarcely a days illness from his childhood to the date of this injury. Gage was

foreman of a gang of men employed in excavating rock, for the road way. The circumstances were
briefly 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 is called, previous to pouring in 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
its 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. The wound thus occasioned will be demonstrated and fully
described to you hereafter. The iron which thus traversed the head, is known with blasters as a
"tamping iron," is round and rendered comparatively smooth by use, and is three feet seven inches
in length, one and one-fourth inches in its largest diameter, and weighs thirteen and one-fourth
pounds. The end which entered first is pointed, the taper being about twelve inches long, and the
diameter of the point one-fourth of an inch.
The patient was thrown upon his back by the explosion, and gave a few convulsive motions of the
extremities, but spoke in a few minutes. His men (with whom he was a great favorite) took him in
their arms and carried him to the road, only a few rods distant, and put him into an ox cart, in which
he rode, supported in a sitting posture, fully three-quarters of a mile to his hotel. He got out of the
cart himself, with a little assistance from his men, and an hour afterwards (with what I could aid him
by taking hold of his left arm) walked up a long flight of stairs, and got upon the bed in the room
where he was dressed. He seemed perfectly conscious, but was becoming exhausted from the
hmorrhage, which, by this time, was quite profuse, the blood pouring from the lacerated sinus in
the top of his head, and also finding its way into the stomach, which ejected it as often as every
fifteen or twenty minutes. He bore his sufferings with firmness, and directed my attention to the hole
in his cheek, saying, "the iron entered there and passed through my head." Pulse at this time 60, soft
and regular. He recognized me at once, and said "he hoped he was not much hurt." His person, and
the bed on which he lay, was one gore of blood. Assisted by my friend Dr. Williams who was first
called to the patient in my absence, we proceeded to examine and dress his wound. From the
appearance of the wound in the top of his head, 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, upward, having very much the shape of

an inverted funnel, the edges of the scalp everted and the frontal bone extensively fractured, leaving
an irregular oblong opening in the skull of two by three and one-half inches. The globe of the left eye
was protruded from its orbit by one-half its diameter, and the left side of the face was more
prominent than the right side. The pulsations of the brain were distinctly seen and felt.
The scalp was shaven, the coagula removed, with three small triangular pieces of the frontal bone,
and in searching to ascertain if there were foreign bodies in the brain, I passed the index finger of
the right hand into the opening its entire length, in the direction of the wound in the cheek, which
received the left index finger in like manner, the introduction of the finger into the brain being
scarcely felt. Aside from the triangular pieces already alluded to as removed, there were two other
pieces detached from the frontal bone, the anterior being two and one-half by two inches, and the
posterior one and one-half by two inches in size, leaving the antero-posterior diameter of the
opening in the skull fully three and one-half inches.
This examination, and the appearance of the iron which was found some rods distant smeared with
blood and brain, together with the testimony of the workmen and of the patient himself, who was
sufficiently conscious to say that the iron "struck his head and passed through," was considered at
the time as sufficiently conclusive, not only of the nature of the accident, but the manner in which it
occurred. The small pieces of bone having been taken away, a portion of the brain, an ounce or
more, which protruded, was removed, the larger pieces of bone replaced, the edges of the soft parts
approximated as nearly as possible, and over all a wet compress, night cap and roller. The face,
hands and arms were deeply burned. The wound in the cheek was left open, the hands and arms
were dressed, and the patient was left with the head elevated, and the attendants directed to keep
him in that position. This was at 7 oclock, P.M. At 10, P.M., same evening, the dressings are
saturated with blood, but the hmorrhage is abating. Has vomited twice only, since being dressed.
Mind clear. Says he "does not care to see his friends, as he shall be at work in a few days." Gives
the names and residence of his friends in Lebanon, N.H. Pulse 65. Constant agitation of his legs,
being alternately retracted and extended like the shafts of a fulling mill.
At 7, A.M., the 14th, has slept some during the night; appears to be in pain; speaks with difficulty;
tumefaction of face considerable, and increasing. Recognizes his mother and uncle. Bleeding into
mouth continues. Asks who is foreman in his pit. Has not vomited since midnight.
On the following day, the 15th, the hmorrhage entirely ceased. Slept well half of the night, and
could see objects indistinctly with the left eye.
For a detailed and daily record of the progress of the case, I will refer you to the Boston Medical and
Surgical Journal of Dec. 13, 1848. It is sufficient for my present purpose to call your attention to a
brief abstract of some of the most important features of the case which followed.

On the 15th Sept., two days after the accident, the patient lost control of his mind, and became
decidedly delirious, with occasional lucid intervals. On that day a metallic probe was passed into the
opening in the top of the head, and down until it reached the base of the skull, without resistance or
pain, the brain not being sensitive.
16th, there began an abundant ftid, sanious discharge from the head with particles of brain
intermingled, finding its way out from the opening in the top of the head, and also from the one in the
base of the skull into the mouth. On the 18th, he slept well nearly all night, but was as incoherent as
ever in the morning. 22d, at 8, A.M., I learn that he has had a very restless night. Throws his hands
and feet about, tries to get out of bed. Head very hot. Says "he shall not live long so." 23d, I find he
has rested and been quiet the most of the night. Appears stronger and more rational. Pulse, which
has varied from 60 to 84 since the injury, I find at 80. The scalp was reshaven and the edges of the
wound brought into apposition as nearly as possible, the edges having sloughed away. The
discharge less in quantity, and less ftid.
At this date, ten days after the injury, vision of the left eye, though quite indistinct before, was totally
lost. Up to this time it had not occurred to me that is waspossible for Gage to recover. The head had
been dressed by myself three times every day; ice water kept on the head and face; the discharges
carefully cleaned off, externally, while the attendants washed the mouth and fauces as often as
necessary, with water and disinfecting solutions. The opening in the top of the head was always
carefully covered with oiled silk underneath the wet compresses. To-day he appears stronger and
more rational than before; calls for food.
Sept. 24th, 9, A.M. I find in my notes, taken at the time, that he has a pulse at 84; vision with right
eye, and hearing with both ears, normal; bowels confined; can tell the day of the week, and time of
day; remembers persons who have visited him and incidents which have transpired since his injury.
This improvement, however, was of short duration, though the discharge from the wounds had
abated. I learned that in the night following he became stupid, did not speak unless aroused, and
then only with difficulty; the integuments between the lower edge of the fracture in frontal bone and
left nasal protuberance, swollen, hot and red, something like an erysipelatous blush. Pulse 96, soft.
Failing strength. Is supported with food and stimulants. During the three succeeding days the coma
deepened; the globe of the left eye became more protuberant, with fungus pushing out rapidly from
the internal canthus. This fungus first made its appearance on the 19th, six days after the injury; also
large fungi pushing up rapidly from the wounded brain, and coming out at the opening in the top of
the head. On the 27th, the swelling upon the forehead fluctuated. The exhalations from the mouth
and head horribly ftid. Pulse 84. Comatose, but will answer in monosyllables when aroused. Will
not take nourishment unless strongly urged. Calls for nothing. Surface and extremities incline to be
cool. Discharge from the wound scanty, its exit being interfered with by the fungi. The friends and
attendants are in hourly expectancy of his death, and have his coffin and clothes in readiness to

remove his remains immediately to his native place in New Hampshire. One of the attendants
implored me not to do anything more for him, as it would only prolong his sufferingsthat if I would
only keep away and let him alone, he would die. She said he appeared like "water on the brain." I
said it is not water, but matter that is killing the manso with a pair of curved scissors I cut off the
fungi which were sprouting out from the top of the brain and filling the opening, and made free
application of caustic to them. With a scalpel I laid open the integuments, between the opening and
the roots of the nose, and immediately there were discharged eight ounces of ill-conditioned pus,
with blood, and excessively ftid. Tumefaction of left side of face increased. Globe of left eye very
prominent.
From this date, Sept. 28th, to Oct. 6th, the discharge from the openings was very profuse and ftid.
Erysipelatous blush on skin of left side of face and head. Pulse ranging from 80 to 96. Speaks only
when spoken to. Swallows well, and takes considerable nourishment, with brandy and milk; says he
has no pain.
Oct. 6thtwenty three days after the injuryI find entered in my note book as follows:General
appearance somewhat improved; pulse 90, and regular; more wakeful; swelling of left side of face
abating; erysipelas gone; opening discharging laudable pus profusely; calls for his pants, and
desires to be helped out of bed, though when lying upon his back cannot raise his head from the
pillow. By turning to one side he succeeded in rising, and sat upon the edge of the bed about four
minutes. Says he feels comfortable. Appears demented, or in a state of mental hebetude.
Oct. 11thtwenty-eight day.Very clear in his mind; states how long he has been upon his bed, how
he was injured, the particulars of the explosion, and the time in the day when it occurred.
Oct. 15ththirty-second day.Progressing favorably. Fungi disappearing; discharging laudable pus
from openings. Takes more food, sleeps well, and says he shall soon go home. Remembers passing
and past events correctly, as well before as since the injury. Intellectual manifestations feeble, being
exceedingly capricious and childish, but with a will as indomitable as ever; is particularly obstinate;
will not yield to restraint when it conflicts with his desires.
Oct. 20ththirty-seventh day.Improving; gets out of and into bed with but little assistance; eats and
sleeps well. Sensorial powers improving, and mind somewhat clearer, but very childish. The fungi
have disappeared. The opening in the top of the head is closing up rapidly, with a firm membranous
tissue.
Nov. 8thfifty-sixty day.Improving in every respect. Sits up most of the time during the day. Appetite
good, though he is not allowed a full diet. Pulse 65. Sleeps well, and says he has not any pain in his

head. He walks down stairs, about the house and into the piazza, and I am informed that he has
been in the street to-day. I leave him to-day, with strict injunctions to avoid excitement and exposure.
Nov. 15thsixty-fourth day.Returned last evening, and learn that Gage has been in the street every
day during my absence, excepting Sunday. Is impatient of restraint, and could not be controlled by
his friends. Making arrangements to go home. Yesterday he walked half a mile, purchased some
articles at the store, inquired the price, and paid the money with his habitual accuracy; did not
appear to be particular as to price, provided he had money to meet it. The atmosphere was cold and
damp, the ground wet, and he went without an overcoat and with thin boots; got wet feet and a chill.
I find him in bed, depressed and very irritable; hot and dry skin; thirst; tongue coated; pulse 110;
lancinating pain in left side of head and face; rigors, and bowels constipated. Ordered cold to the
head and face, and a cathartic, to be taken and repeated if it does not operate in six hours.
Nov. 16th, A.M.No better. Cathartic has operated freely. Pulse 120; has passed a sleepless night;
skin hot and dry; pain and thirst unabated. Was bled from the arm xvi., and got:. Hydrag.
chloridi, gr. x.; ipeacac, gr. ij. M.
8, P.M., same day.Pulse falling; heat and pain moderated. Took a solution of ant. pot. tart. during
night, and slept well.
17th, A.M.Much improved. Has been purged freely during night, and says he feels better every
way. Has no pain in head.
18th.Is walking about house again, free from pain in head, and appears to be in a way of
recovering, if he can be controlled. Has recently had several pieces of bone pass into the fauces,
which he expelled from the mouth. The discharge from the head very slight, and the opening steadily
closing up.
On the 25th he was taken, in a close carriage, a distance of thirty miles, to Lebanon, N. H., his
home, where I saw him the succeeding week, and found him going on well. He continued to improve
steadily, until on Jan. 1, 1849, 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. Gage passed the
succeeding winter months in his own house and vicinity, improving in flesh and strength, and in the
following April returned to Cavendish, bringing his "iron" with him.
He visited me at that time, and presented something like the following appearances. 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 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
elevationa 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 left side of face. His physical health is good, and I am inclined
to say that he has recovered. Has no pain in 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 his 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 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."
His mother, a most excellent lady, now seventy years of age, informs me that Phineas was
accustomed to entertain his little nephews and nieces with the most fabulous recitals of his
wonderful feats and hair-breadth escapes, without any foundation except in his fancy. He conceived
a great fondness for pets and souvenirs, especially for children, horses and dogsonly exceeded by
his attachment for his tamping iron, which was his constant companion during the remainder of his
life. He took to travelling, and visited Boston, most of the larger New England towns, and New York,
remaining awhile in the latter place at Barnum's, with his iron. In 1851 he engaged with Mr. Jonathan
Currier, of Hanover, New Hampshire, to work in his livery stable. He remained there, without any
interruption from ill health, for nearly or quite a year and a half.
In August, 1852, nearly four years after his injury, he turned his back upon New England, never to
return. He engaged with a man who was going to Chili, in South America, to establish a line of
coaches at Valparaiso. He remained in Chili until July, 1860, nearly eight years, in the vicinity of

Valparaiso and Santiago, occupied in caring for horses, and often driving a coach heavily laden and
drawn by six horses. In 1859 and '60 his health began to fail, and in the beginning of the latter year
he had a long illness, the precise nature of which, I have never been able to learn. Not recovering
fully, he decided to try a change of climate, and in June, 1860, left Valparaiso for San Francisco,
where his mother and sister resided. The former writes that "he arrived in San Francisco on or about
July 1st, in a feeble condition, having failed very much since he left New Hampshire. He suffered
much from seasickness on his passage out from Boston to Chili. Had many ill turns while in
Valparaiso, especially during the last year, and suffered much from hardship and exposure."
After leaving South America I lost all trace of him, and had well nigh abandoned all expectation of
ever hearing from him again. As good fortune would have it, however, in July, 1866, I was able to
learn the address of his mother and very soon commenced a correspondence with her and her
excellent son-in-law, D. D. Shattuck, Esq., a leading merchant in San Francisco. From then I learned
that Gage was deadthat after he arrived in San Francisco his health improved, and being anxious
to work, he engaged with a farmer at Santa Clara, but did not remain there long. In February, 1861,
while sitting at dinner, he fell in a fit, and soon after had two or three fits in succession. He had no
premonition of these attacks, or any subsequent ill feeling. "Had been ploughing the day before he
had his first attack; got better in a few days, and continued to work in various places," could not do
much, changing often, "and always finding something which did not suit him in every place he tried."
On the 18th of May, 1861, three days before his death, he left Santa Clara and went home to his
mother. At 5 oclock, A.M., on the 20th, he had a severe convulsion. The family physician was called
in, and bled him. The convulsions were repeated frequently during the succeeding day and night,
and he expired at 10, P.M., May 21, 1861twelve years, six months and eight days after the date of
his injury. These convulsions were unquestionably epileptic. It is regretted that an autopsy could not
have been had, so that the precise condition of the encephalon at the time of his death might have
been known. In consideration of this important omission, the mother and friends, waiving the claims
of personal and private affection, with a magnanimity more than praiseworthy, at my request have
cheerfully placed this skull (which I now show you) in my hands, for the benefit of science. [2]
I desire, here, to express gratefully my obligations, and those of the Profession, to D. D. Shattuck,
Esq., brother-in-law of the deceased; to Dr. Coon, Mayor of San Francisco, and to Dr. J. D. B.
Stillman, for their kind cooperation in executing my plans for obtaining the head and tamping iron,
and for their fidelity in personally superintending the opening of the grave and forwarding what we so
much desired to see.
The missile entered, as previously stated, immediately anterior and external to the angle of the
interior maxillary bone, proceeding obliquely upwards in the line of its axis, passed under the
junction of the superior maxillary and malar bones, comminuting the posterior wall of the antrum,
entered the base of the skull at a point, the centre of which is one and one-fourth inches to the left of

the median line, in the junction of the lesser wing of the sphenoid with the orbitar process of the
frontal bonecomminuting and removing the entire lesser wing, with one-half of the greater wing of
the sphenoid bonealso fracturing and carrying away a large portion of the orbitar process of the
frontal bone, leaving an opening in the base of the cranium, after the natural efforts at repair by the
deposit of new bone, of one inch in its lateral, by two inches in its antero-posterior diameters, with a
line of fracture or fissure leading anteriorly through the orbitar plate of the frontal bone, the anterior
fossa, and deflecting laterally, towards the median line, divides the left frontal sinus, at the supraorbitar notch, and ascends the forehead along the left margin of the ridge, for the attachment of the
falx major. Inferiorly the line of separation begins at the infra-orbitar foramen and the malar process
of the supra-maxillary from the body of the bone, terminating at a point upon the superior maxillary
opposite the last molar tooth.The bones implicated in its passage were the superior maxillary,
malar, sphenoid, and frontal. The iron, as you will perceive, entered the left cerebrum at the fissure
of Sylvius, possibly puncturing the cornu of the left lateral ventricle, and in its passage and exit must
have produced serious lesion of the cerebrumdisintegrating and pulpifying it, drawing out a
considerable quantity of it at the opening in the top of the head, and lacerating unquestionably the
upper aspect of the falx major and the superior longitudinal sinus. As the iron emerged from the
head, it comminuted the central portion of the frontal bone, leaving an irregular oblong opening in the
bone of three and one-half inches in its antero-posterior, by two inches in its lateral diameter. Two of
these fragments, as you will see from the specimens before you, were re-united. [3]
Remarks.
I. No attempt will be made by me to cite analogous cases, as after ransacking the literature of
surgery in quest of such, I learn that all, or nearly all, soon came to a fatal result. Hence I conclude
to leave that task to those who have more taste for it. This case is chiefly interesting to me, as
serving to show the wonderful resources of the system in enduring the shock and in overcoming the
effects of so frightful a lesion, and as a beautiful display of the recuperative powers of nature. It has
been said, and perhaps justly, that "the leading feature of this case is its improbability." (BIGELOW .)
This may be so, but I trust, after what has been shown you to-day, that the most skeptical among
you have been convinced of its actual occurrencethat it was no "Yankee invention," as a
distinguished Professor of Surgery in a distant city was pleased to call it. Moreover, it would seem,
when we take into account all the favoring circumstances, that we may not only regard partial
recovery as possible, but exceedingly probable. These I will name briefly.
1st. The subject was the man for the case. His physique, will, and capacity of endurance, could
scarcely be excelled.
2d. The shape of the missilebeing pointed, round and comparatively smooth, not leaving behind it
prolonged concussion or compression.

3d. The point of entrance outside of the superior maxillary bonethe bolt did little injury until it
reached the floor of the cranium, when, at the same time that it did irreparable mischief, it opened up
its way of escape, as without this opening in the base of the skull, for drainage, recovery would have
been impossible.
4th. The portion of the brain traversed, was, for several reasons, the best fitted of any part of the
cerebral substance to sustain the injury. II. This case has been cited as one of complete recovery, it
being often said that a very considerable portion of the left cerebrum was lost, without any
impairment to the intellect. I think you have been shown that the subsequent history and progress of
the case only warrant us in saying that, physically, the recovery was quite complete during the four
years immediately succeeding the injury, but we learn from the sequel that ultimately the patient
probably succumbed to progressive disease of the brain. Mentally the recovery certainly was only
partial, his intellectual faculties being decidedly impaired, but not totally lost; nothing like dementia,
but they were enfeebled in their manifestations, his mental operations being perfect in kind, but not
in degree or quantity. This may perhaps be satisfactorily accounted for in the fact that while the
anterior and a part of the middle lobes of the left cerebrum must have been destroyed as to function,
its functions suspended, its fellow was left intact, and conducted its operations singly and feebly.
III. Little has been said in the foregoing account as to the treatment or conduct of this case, this
being regarded as quite unnecessary. The initiatory treatment, received from the iron, though it might
not be well received in this presence, you will permit me to say, was decidedly antiphlogistic, a very
large amount of blood having been lost. May we not infer that this prepared the system for the trying
ordeal through which it was about to pass? The recovery is attributed chiefly to the vis vita, vis
conservatrix, or, if you like it better, to the vis medicatrix natur, of which this case is a striking
exemplification.
I desire to call your attention, in passing, to two critical periods in the progress of the case, when
what was done undoubtedly changed the tendency to a fatal result. The first was on the fourteenth
day, when the large abscess, which probably communicated with the left lateral ventricle, was
opened, followed by a marked improvement in all the symptoms. The second was on the sixty-fourth
day, at which time he was bled sixteen ounces.
I indulge the hope, that surely but little if anything was done to retard the progress of the ease, or to
interfere with the natural recuperative powers. Nature is certainly greater than art. Some one has
wisely said, that vain is learning without wit. So may we say, vain is art without nature. For what
surgeon, the most skilful, with all the blandishments of his art, has the world ever known, who could
presume to take one of his fellows who has had so formidable a missile hurled through his brain,
with a crash, and bring him, without the aid of this vis conservatrix, so that, on the fifty-sixth day

thereafter, he would have been walking in the streets again? I can only say, in conclusion, with good
old Ambrose Par, I dressed him, God healed him.
Fig. 1.

View of the tamping iron, and front view of the cranium, showing their comparative size.

Fig. 2.

Front and lateral view of the cranium, representing the direction in which the iron traversed its cavity;
the present appearance of the line of fracture, and also the large anterior fragment of the frontal
bone, which was entirely detached, replaced, and partially re-united.

Fig. 3.

View of the base of the skull from within; the orifice caused by the passage of the iron having been
partially closed by the deposit of new bone.

1. Jump up Soon after the publication of this case in the Boston Medical and Surgical Journal,
in November, 1848, I received a letter from Henry J. Bigelow, Professor of Surgery in the

Medical Department of Harvard University, requesting me to send Gage to Boston,

generously proposing to defray his expenses and compensate him for loss of time. Gage
being quite well, and the hole in the top of his head entirely closed, accepted this
proposition, and remained in Boston, under the observation of Prof. Bigelow, eight or nine
weeks, where he was examined by many medical men, Prof. Bigelow being thoroughly
convinced, at a time when the accident had very few believers either in the medical
profession or out of it, that the lesion was as representedthat the iron had traversed the
cranium and brain as stated. With my concurrence he reported the case, with illustrations, in
the American Journal of the Medical Sciences for July, 1850.
2. Jump up The skull and iron have been deposited, by the writer, in the Museum of the
Medical Department of Harvard University, in Boston.
3. Jump up See plates at the end of this article, showing the direction of the passage of the
bar, lines of fracture in the skull and the comparative size of the iron and head.