Surgery of The Mind

Peer-Review Reports
FRONTIERS
Surgery of the Mind, Mood, and Conscious State: An Idea in Evolution
R. Aaron Robison, Alexander Taghva, Charles Y. Liu, Michael L. J. Apuzzo
Since the beginning of recorded history, humans have sought

a physical means of altering disordered behavior and consciousness. This quest has spawned numerous innovations in
neurosurgery and the neurosciences, from the earliest prehistoric attempts at trepanation to the electrocortical and anatomic localization of cerebral function that emerged in the 19th
century. At the start of the 20th century, the overwhelming
social impact of psychiatric illness intersected with the novel
but imperfect understanding of frontal lobe function, establishing a decades-long venture into the modern origin of psychosurgery, the prefrontal lobotomy. The subsequent social and
ethical ramifications of the widespread overuse of transorbital
lobotomies drove psychosurgery to near extinction. However,
as the pharmacologic treatment of psychiatric illness was
established, numerous concomitant technical and neuroscientific innovations permitted the incremental development of a
new paradigm of treating the disordered mind. In this article,
we retrospectively examine these early origins of psychosurgery and then look to the recent past, present, and future for
emerging trends in surgery of the psyche. Recent decades
have seen a revolution in minimalism, noninvasive imaging,
and functional manipulation of the human cerebrum that have
created new opportunities and treatment modalities for disorders of the human mind and mood. Early contemporary efforts
were directed at focal lesioning of abnormal pathways, but
Key words
Deep brain stimulation
Functional neurosurgery
Neuromodulation
Prefrontal lobotomy
Psychosurgery
Trepanation
Vagal nerve stimulation
Abbreviations and Acronyms
BRW: Brown-Roberts-Wells
CRW: Cosman-Roberts-Wells
CT: Computed tomography
DBS: Deep-brain stimulation
DTI: Diffusion tensor imaging
MDD: Major depressive disorder
MRI: Magnetic resonance imaging
OCD: Obsessive-compulsive disorder
PET: Positron-emission tomography
PTSD: Posttraumatic stress disorder
S2
www.SCIENCEDIRECT.com
deep-brain stimulation now aims to reversibly alter and

modulate those neurologic activities responsible for not only
psychiatric disorders, but also to modulate and even to
augment consciousness, memory, and other elements of cerebral function. As new tools become available, the social and
medical impact of psychosurgery promises to revolutionize not
only neurosurgery, but also humans capability for positively
impacting life and society.
INTRODUCTION
Since the beginning of human existence, the desire to modify human
behavior and consciousness through indirect or direct physical intervention has been a holy grail. Throughout history, these efforts
have taken many different directions, with the rst millennia characterized by largely shamanistic or ritualistic interventions or trepanations with little understanding of the underlying physiology or
therapeutic effect. In the past century, an exponential increase in our
awareness of the diversity and the prevalence of diseased states of
the human mind combined with the increasing technical and technological sophistication of our interactions with the human cerebrum have created an unprecedented opportunity (7). The epidemiology of psychiatric illness and other diseases of the mind and
conscious state is staggering5 of the top 10 causes of disability
worldwide are psychiatric and neurobehavioral disorders (96). It is
Department of Neurological Surgery, Keck School of Medicine, University of

Southern California, Los Angeles, California, USA
To whom correspondence should be addressed: R. Aaron Robison, M.D.
[E-mail: rrobison@usc.edu]
Archival Article Citation: World Neurosurg. (2012) 77, 5-6:662-686.
http://dx.doi.org/10.1016/j.wneu.2013.08.002
Journal homepage: www.WORLDNEUROSURGERY.org
Available online: www.sciencedirect.com
1878-8750/$ - see front matter 2012 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2013.08.002
PEER-REVIEW REPORTS: FRONTIERS

R. AARON ROBISON ET AL.
Figure 1. Neolithic trepanation circa 5100 BC (A), with evidence of postoperative healing (B) (2).
estimated that the incidence of major depression alone in a single individuals lifetime is between 12%18%, and with greater than 120 million patients, it represents the greatest cause of disability worldwide (5).
The remainder of the top 10 includes alcoholism (fourth), bipolar disorder (sixth), schizophrenia (ninth), and obsessive-compulsive disorder (tenth) (96). In the case of major depression, as many as one third of
patients become resistant to treatment (30).
As the enormous prevalence and social cost of psychiatric disease
continues to gain recognition, with concomitant improvements in
the efcacy and safety of surgical intervention, surgery of the mind
and mood promises to become one of the most epidemiologically
important elds of neurosurgery. Although psychosurgery has
many varying connotations and denitions, particularly the narrow
category of ablative lobotomies, which drew popular attention and
criticism in the middle of the 20th century, in this article it is dened
as the full spectrum of neurosurgical treatments for psychiatric illness, including all the various modalities of open, stereotactic, functional, and radiosurgical procedures.
SURGERY OF THE MIND, MOOD, AND CONSCIOUS STATE
for trauma or depressed skull fractures associated with the bludgeoning-type weapons of the day, there is also evidence to suggest that the
operation was conducted for other ailments as well, including the shamanistic exorcism of malicious spirits, a possible cultural proxy for
mental illness, epilepsy, depressed consciousness, or even the restoration of life itself.
There is also mention of trepanation in the classical writings of Hippocrates and Galen, and evidence suggests it was practiced throughout
the early Medieval period. After an apparent lull, trepanation returned to
prominence in the Renaissance era, with many references and depictions of the procedure in contemporary medical texts and artwork of the
time. One notable example is The Cure of Folly or The Extraction of the Stone
of Madness, a painting by the 15th-century Dutch painter Hieronymus
Bosch (Figure 3). Although many portions of the painting are pointedly
allegorical, it nonetheless depicts the extraction of a brain stone as a
cure for either stupidity or madness, depending on the interpretation of
the term folly (111). The idea that madness could be caused by a
physical stone in the brain was a common superstition at the time,
although it is unclear to what extent trepanation was performed to that
purpose. Although there is some more contemporary evidence of the
use of trepanation in certain African tribes, with the advent of the later
Renaissance understanding of physiology and naturalism, the use of
trepanation as a form of metaphysical treatment of psychiatric illness
passed from Western medical practice until its reincarnation in the 20th
century (130).
THE ABLATIVE ERA OF PSYCHOSURGERY
The Origins of Functional Neuroanatomy
Although classical philosophers such as Aristotle and Descartes
were some of the rst to postulate that the brain was the center of
Trepanation
The history of psychosurgery predates the start of recorded history
itself. Numerous reports exist of prehistoric examples of trepanation.
Although the therapeutic purpose of trepanation is open to speculation,
it likely included the treatment of psychiatric illness. The most welldocumented example is a skull found in the Neolithic burial site of
Ensisheim in Alsace, France, which dates to roughly 5100 BC (Figure 1)
(2). The skull had two separate areas of trepanation and evidence of
subsequent healing, indicating that the lesions were performed intentionally while the individual was still alive, as opposed to an epiphenomenon such as infection or postmortem trauma, and that the individual
survived for an extended period of time after the procedure. This example represents not only the earliest form of neurosurgery or psychosurgery but of a surgical procedure of any kind. There is also extensive
archeological evidence of trepanation in pre-Columbian Mesoamerica,
with the most numerous examples originating in Peru and Bolivia,
where the procedure was practiced with considerable skill, as evidenced
by the number of skulls with evidence of postoperative healing, as well
as the associated archeological trove of tools developed for the purpose
(Figure 2) (122). Although the majority of these were likely performed
WORLD NEUROSURGERY 80 [3/4]: S2-S26, SEPTEMBER/OCTOBER 2013
Figure 2. Surgical knives (known as tumi) used for

trepanation among pre-Columbian civilizations of South
American, circa 100-1100 AD (courtesy Paleo Direct,
Altamonte Springs, FL).
www.WORLDNEUROSURGERY.org
S3

Figure 4. Franz Joseph Gall, founder of phrenology, and his original

manuscript from 1819. Gall proposed that different portions of the brain
had discrete functions.
Figure 3. The Cure of Folly or The Extraction of the Stone of

Madness, a painting by the 15th-century Dutch painter Hieronymus
Bosch depicting the cure for psychiatric illness or madness.
conscious thought, the modern grandfather of neuroanatomy was

arguably the German physician Franz Joseph Gall, the progenitor of
phrenology (Table 1) (118). In 1819 he published his landmark work
The Anatomy and Physiology of the Nervous System in General, and of the
Brain in Particular, with Observations upon the Possibility of Ascertaining the
Several Intellectual and Moral Dispositions of Man and Animal, by the Conguration of their Heads (Figure 4). Together with Johann Spurzheim, he
successfully propagated phrenology throughout Victorian society.
Although phrenology was never accepted as a viable theory by the
prevailing medical and scientic communities of the time, Galls con-
Table 1. Important Landmarks in the Early Development of Psychosurgery

Date
Event
circa 5100 BC
First confirmed finding of prehistoric trepanation
1819
Franz Joseph Gall publishes landmark work on phrenology, suggesting the brain has discrete functional anatomic regions
1848
John Harlow describes the frontal-lobe syndrome in Phineas Gage, a railroad worker impaled with a steel rod
1865
Pierre Broca localizes speech faculties to the frontal lobe
1870
Gustav Fritsch and Eduard Hitzig perform stimulation of cerebral cortex in dogs for localization of functional cortex
1876
David Ferrier expands cortical stimulation and localization to primate models
1888
Gottlieb Burckhardt performs the first topectomy for the treatment of psychiatric disease
1910
Lodovicus Puusepp sections cortex between frontal and parietal lobes in manic depressive patients
1930s
Walter Dandy, Wilder Penfield, and Joseph Evans publish accounts describing modifications of mood disturbances with frontal lesion resections
1935
John Fulton and Carlyle Jacobsen present work on primate postlobectomy behavior
1935
Egas Moniz and Almeida Lima perform their first frontal leucotomy in humans
1936
Walter Freeman and James Watts introduce the lobotomy to the United States
1946
Walter Freeman popularizes the transorbital lobotomy based on a technique developed by Amarro Fiamberti
1953
Introduction of chlorpromazine, the first successful antipsychotic agent, in Europe under the name Largactil, subsequently introduced in the
United States as Thorazine
1974
Passage of the National Research Act in the United States with the subsequent release of the Belmont Report
S4

cept of the brain as containing

discrete anatomic areas responsible for various neurological functions and anomalies was nonetheless the
precursor for the modern understanding of brain function, particularly the modularity of the mind theory that
underpins much of modern
psychosurgery. Much of
Galls seminal work was later
lost amidst the controversy
that erupted around the pseuFigure 5. Gottlieb Burckhardt, a Swiss
psychiatrist and the first to attempt
doscience of phrenology, but
the surgical treatment of psychiatric
he remained the rst to postuillness in the modern era in 1888.
late and attempt to describe
the discrete functional organization of the brain.
Shortly after Galls thesis, a more scientic approach to functional neuroanatomy based on the same localizationist concept
was derived from the study of survivors of traumatic brain injuries
and the derivation of functional localization based on associated
patterns of lesioning and behavior. The most recognized of these
was Phineas Gage, a young railway worker who was constructing a
railroad line when an accidental explosion drove a meter-long steel
rod into his head. The rod penetrated his left maxilla and traversed
his frontal lobe before exiting the superior portion of the skull and
resulted in a classic frontal syndrome with poor impulse control and
executive functioning. Gage was seen by a local physician, John M.
Harlow, who ultimately described his ndings in the precursor of
the New England Journal of Medicine in 1848 (51). The work of Harlow
and his contemporaries ultimately gave rise to the neuroscientic
work of the latter part of the 19th century, when a combination of
animal experiments and human cadaveric studies helped to elucidate the associations between function and anatomy.
One of the earliest proponents of the functional anatomic localization theories of Gall was Jean Baptiste Bouillaud, a French physician
who went on to become Dean of the prestigious Charit Hospital in
Paris and President of the French Academy of Medicine (22). He dissociated the better ideas of Gall from that of phrenology and attempted to
elucidate the localization of speech faculties on the basis of a number of
frontal lobe lesions. His work was followed by that of Pierre Paul Broca,
and his series of patients with what he initially termed aphemia but
was subsequently titled aphasia by Armand Trousseau, who was followed by Carl Wernicke and his work (133). In 1870 Gustav Fritsch and
Eduard Hitzig contemporaneously extended the understanding of localization by performing stimulations of the cortex of dogs, in which
they elucidated the location of the motor cortex, which was subsequently expanded into primate models by David Ferrier (32, 37).
The Birth of Modern Psychosurgery
A natural conclusion of this evolving understanding of brainbehavior associations was that pathologic mental or psychiatric states
were potentially associated with a specic area of cortex, the removal
of which could potentially alleviate the patients condition. This idea
was rst acted upon by the Swiss psychiatrist Gottlieb Burckhardt
(Figure 5). After assuming directorship of the Prfargier Asylum in

his native Switzerland, on December 29, 1888, he performed the rst
psychosurgery of the modern era, with an experimental topectomy
on a patient with intractable psychiatric illness (23). He went on to
perform topectomies on a total of six patients, in some cases doing
up to four procedures on the same patient. The locations of the
topectomies were based largely on the supposed localization of
aggressive behavior derived from the work of his contemporaries,
predominantly in the temporal and parietal lobes.
Burckhardt published a report of his experience in 1891, in which
he described three of the procedures as successes, two as partial
successes, and one which resulted in the death of the patient (64).
Despite the functionally eloquent location of his topectomies, he
made little mention of any associated postoperative decits. After
his initial report was met with signicant disapproval by his peers,
Burckhardt did not pursue his experiments any further.
Before the advent of the frontal lobotomy, only one other physician,
the Estonian neurosurgeon Lodovicus Puusepp, attempted to treat psychiatric disease via surgery (102). In 1910, without therapeutic success,
he sectioned the cortex between the frontal and parietal lobes in three
patients with manic depression. With the increased safety and survivability of operative neurosurgery in the early 20th century, a number of
neurosurgeons and neurologists noted the resolution or creation of
psychiatric symptoms with the resection of various tumors or other
pathologies. Walter Dandy, Wilder Peneld, and Joseph Evans all published such accounts in the 1930s, but the psychiatric outcomes were
generally incidental to the purpose of the resection (21, 100).
The nal precursor to the era of the frontal lobotomy was the work
of the American neuroscientist John Farquhar Fulton (Figure 6).
Fulton initially obtained his bachelors degree from Harvard and
then proceeded to study neuromuscular physiology under Sir
Charles Sherrington at Oxford University. He subsequently returned
to the United States and worked with Harvey Cushing at the Peter
Bent Brigham Hospital before obtaining a medical degree and ultimately establishing his own primate neurophysiology laboratory as
chairman of Physiology at Yale Medical School. Along with Carlyle
Figure 6. John Fulton, an American physiologist who studied the

behavioral effects of frontal-lobe resections in the 1930s, which formed
the basis of subsequent clinical lobotomies.
S5

Jacobsen, Fulton attempted

to map the primate brain by
removing specic portions
of the cortex and observing
the animals for decits or
abnormal behavior.
In 1935, at the Second International
Neurologic
Congress in London, they
presented the results of an
experiment on two chimpanzees in which they resected rst the unilateral
and then the contralateral
frontal association cortex,
and after bilateral resection
Figure 7. Antnio Egas Moniz, a
were noted to be devoid of
Portuguese neurologist who initiated
emotional expression and
frontal lobotomies in humans with
had loss of the frustrapsychiatric disorders in humans in
1935, eventually sharing the Nobel
tional behavior previously
prize for his efforts.
noted when they failed to receive an anticipated reward
(39). Among the attendees
at the Congress that year
was Antonio Egas Moniz, a Portuguese neurologist who at the time
was gaining recognition for his ground-breaking collaboration with
the neurosurgeon Almeida Lima on the development of cerebral
angiography, as well as an American neuropsychiatrist, Walter Freeman, who was presenting his work on ventriculography. Both
Moniz and Freeman took a keen interest in the Fultons presentation, and were the rst to nally successfully carry it out to a therapeutic conclusion.
The Socioeconomic Context of Psychosurgery
To understand the rapid explosion of psychosurgery that occurred during the following decades, characterized at that juncture by the frontal
lobotomy, it is rst necessary to understand the social context in which
these medical advances were being made. A 1937 report on the state of
mental illness in the United States estimated that there were more than
450,000 patients institutionalized in 477 asylums, with nearly one half
of them hospitalized for ve years or longer (28). Of the institutional
beds available, one third were characterized as substandard. In addition, at an estimated cost per day of $2.36 at the time, the total cost of
caring for all patients estimated to have debilitating mental illness
would have exceeded $24 billion in todays dollars (129).
The endemic prevalence of tertiary syphilis in the pre-penicillin era as
well as the ood of veterans and victims of World War I left with psychiatric trauma signicantly contributed to the epidemiologic burden of
mental illness. In addition, in the absence of any psychotropic medications at time, the only recourse for treatment of incapacitating mental
illness was essentially institutionalization and physical restraint. The
resulting scenes of degradation and occasionally horric conditions
were carried by the media to an appalled public, creating an atmosphere
in which any treatment that offered the hope of a cure, no matter the
means, could nd acceptance.
The practice of psychiatry itself was also in ux, with divisions
within the eld of psychiatry as well as neurology over how to diag-
S6
nose and treat mental illness. The eld of psychiatry was divided into
two distinct philosophies, with the functional approach of Sigmund
Freud favoring psychotherapy and the somatic approach of Emil
Kraeplin advocating aggressive intervention, including options
such as electroconvulsive therapy or an insulin or metrazol-induced
coma (106). In addition, as psychiatry became increasingly practiced
within the cloistered environment of asylums, psychiatrists became
further and further removed from the mainstream of medical
thought, and in many cases neurologists entered the forefront of the
diagnosis and treatment of mental illness.
The Frontal Leucotomy

One such neurologist was Egas Moniz, initially born Antonio Caetano
de Abreu Freire in 1874 (Figure 7). A man of many pursuits, Moniz was
politically active, intermittently punctuating his medical career by serving the Portuguese parliament as well as assuming a number of prominent roles in Portugals international relations, including as the Minister of Foreign Affairs in 1918. Initially educated at the University of
Coimbra, after training in Paris under Babinski and Dejerine, Moniz
eventually assumed the role of chairman of Neurology at the newly
founded department at the University of Lisbon in 1911. Moniz was
most well-known for his pioneering work in the development of cerebral angiography, for which he was twice nominated and eventually
received the Nobel Prize in Physiology and Medicine in 1949. Upon
returning from the Congress in 1935, he approached his colleague and
long-time collaborator Almeida Lima, and on November 12, 1935, they
performed arguably the rst successful psychosurgery by injecting alcohol into the white matter of the frontal lobe of a 63-year-old woman
with paranoid delusions, anxiety, and melancholia (Figure 8) (31).
Moniz, who had severe gout and was unable to perform the surgeries
himself, along with Lima, initially practiced the procedure on a cadaver,
injecting the alcohol through a lateral trepanation in the skull into the
centrum semiovale of the frontal lobe, a location selected for its relative
avascularity and abundance of white matter connections between the
anterior frontal lobe and the remainder of the cortex and thalamus.
Although their rst patient
suffered from signicant apathy and a blunted affect after
the procedure, they declared
it an overall success in ridding the patient of her psychosis.
They termed the procedure a frontal leucotomy and
performed injections on
seven additional patients.
The need for multiple injections and unpredictable
tracking of the alcohol
prompted Moniz to rene
the method, and he subsequently introduced the leuFigure 8. Almeida Lima, a Portuguese
cotome, an instrument capaneurosurgeon who collaborated with
Moniz in performing the first frontal
ble of cutting precise
lobotomies for psychiatric disease in
centimeter-sized
lesion
humans in 1935.
within the white matter

Figure 9. An illustration from one of Egas Moniz manuscripts in 1936

showing his leucotome instrument and the manner in which the
lobotomy was performed (A) and a later version of his leucotome that
used a retractable cutting wire (B).
(Figure 9). After completing these procedures in 20 patients, Moniz

and Lima published their results in Le Bulletin de lAcademie de Medecine
in March 1936, barely four months after completing their rst experiment (95). Although there was little follow-up or objective data
included in the report, Moniz reputation, established by his political prominence and previous angiography research, lent legitimacy
to his ndings and to the procedure.
After Moniz report, the procedure was adopted by a number of
practitioners throughout Europe and the Americas. One early advocate of the procedure was the American neurologist Walter Freeman,
who was impressed by the
ideas of Fulton and the reported success of Moniz
(Figure 10). Freeman came
from a family of physicians,
and his grandfather, W. W.
Keen, was a well-regarded
surgeon in the American
Civil War. He performed his
undergraduate studies at
Yale University and completed medical school and
was trained as a neurologist
at the University of Pennsylvania in Philadelphia, where
he was raised. When rebuffed in his effort to obtain
Figure 10. Walter Freeman, the
a position in Philadelphia,
American neurologist who introduced
he obtained a position at St.
the lobotomy for psychiatric
disorders to the United States in
Elizabeths Hospital in
1936 and later popularized the
Washington, DC, and after
transorbital lobotomy.
obtaining a doctorate in
neuropathology, he subsequently became the rst

neurologist to join the faculty of George Washington
University (77).
At George Washington
he worked with James
Watts, who comprised the
Department of Neurosurgery at George Washington
(Figure 11). On September
14, 1936, they performed the
rst frontal lobotomy in the
United States on Alice Hood
Hammatt, a 63-year-old
housewife from Topeka,
Kansas, who reportedly sufFigure 11. James Watts, the
fered from depression, anxAmerican neurosurgeon who
iety, and insomnia after she
collaborated with Walter Freeman in
developing the transorbital lobotomy
became lost at night in New
for treatment of psychiatric disease
York City (36).The patient
(circa 1940).
developed evidence of some
language and psychomotor
changes postoperatively but
apparently remained calm
and devoid of her previous anxiety.
Freeman and Watts were so encouraged by this relative success
that they rapidly accumulated a series of 20 patients (Figure 12).
However, they noted that Monizs technique was awed because
many patients developed recurrent symptoms after the procedure
(36). Consequently they began to experiment with modications to
the procedure by using iodinated oil and cranial x-rays to assess the
location of the leucotomy. They noted signicant variations in the
actual location of the leucotomies with only minimal variations in
the entry point or angle of the leukotome. They consequently developed strict anatomic landmarks for the placement of burr holes and
angulation of the leukotome. Freeman also made a modied, calibrated leukotome based on Monizs instrument, which he referred
to as the precision leukotome.
With additional experimentation, Freeman developed an increasing appreciation of the pathologic complexity of psychiatric illness,
and, using his experience in neuropathology, undertook postmortem examinations of the patients, in which he noted retrograde
degeneration in specic areas of the thalamus. This led Freeman to
assume that the thalamus was the center of affective experience, and
based on the growing understanding of contemporary neuroanatomists and physiologists regarding the white matter tracts distributed
between the frontal lobes and projecting to the thalamus and other
areas of cortex, he surmised that if one could specically target the
appropriate white matter tracts of the frontal lobe, it would be feasible
to treat specic degrees or types of affective or psychotic disorders.
This discovery led to the development of three different types of
lobotomies, the minimal, standard, and radical. Minimal lobotomies were placed more anteriorly and were used for patients with
predominantly affective symptoms, whereas radical lobotomies
were extended more posteriorly and medially and were reserved for
patients with schizophrenia or treatment failures. However, despite
S7

Figure 12. Walter Freeman (center, standing) performing a transorbital

lobotomy, circa 1940.
the use of the precision method and x-rays, Freeman and Watts
reported frequent uncontrolled bleeding, particularly with more
posterior or medial leucotomies, often resulting in death, as well as
a constellation of associated neuropsychiatric changes, including
seizures and what was described as the frontal lobe syndrome,
consisting of apathy, inattention and socially inappropriate behavior. In 1942 Freeman and Watts wrote a monograph describing their
rst 200 cases, of which 63% improved postoperatively, 23% had no
change, and 14% had a negative outcome, including the aforementioned fatalities.
At this time Freeman became interested in a technique described
by an obscure Italian psychiatrist named Amarro Fiamberti, in
which an alcohol leucotomy was performed via the use of a transorbital technique (Figure 13). A rm believer in the success of the
frontal lobotomy in treating and decreasing the burden of psychiatric illness, Freeman saw this as an opportunity to expand the reach of
the procedure by removing the need for a neurosurgeon to obtain
cranial access, thus allowing a broader range of practitioners to
provide the procedure. He modied Fiambertis technique and developed a system whereby the patient was rendered unconscious
with an electroshock treatment, and a modied ice-pick orbitoclast
was used to penetrate the roof of the orbit with a mallet, after which
the orbitoclast was inserted to a depth of 7 cm and swept laterally by
15 (Figure 14) (101). This enabled Freeman to perform the procedure without the need for either a neurosurgeon or anesthetist and to
do so in nearly any setting. Freeman then set off on an evangelistic
cross-county tour to popularize his technique.
Horried by the crude manner in which the procedure was performed, and the substandard perioperative care provided, including
the conspicuous absence of sterile technique, James Watts and the
remainder of the neurosurgical establishment became disenchanted
with the transorbital lobotomy, and Watts and Freeman parted ways
shortly thereafter. Despite the complications that resulted from lack
of sterile technique, crude instruments, lack of anesthesia care or
perioperative monitoring, as well as fatalities resulting from intra-
S8
cranial hemorrhage, Freeman went on to perform nearly 4000 of the

procedures (Figure 15) (54).
Freeman was an adept publicist, and via the selective and sensational reports of the procedure that were released through the mainstream press, the practice of frontal lobotomies gained traction
amongst the public. Despite resistance and reservations in the
broader medical community, many psychiatrists and nonsurgical
practitioners seized on the procedure as a new last resort for patients
who lacked any effective alternative treatments. The transorbital
lobotomy soon became ubiquitous across the landscape of psychiatric care in the United States and many parts of Europe. An estimated 60,000 procedures were performed throughout the two decades spanning from 1936 to 1956; they were performed in a variety
of contexts, including asylums, veterans affairs hospitals, academic
medical centers, and even in ofces and ad-hoc operating rooms
set up in motel rooms.
Demonstrative of the widespread social acceptance of the procedure was the inclusion of a number of public gures amongst patients receiving the procedure, including the actress Frances Farmer,
Rose Williams, the sister of Tennessee Williams, and Rosemary
Kennedy, the younger sister of John F. Kennedy. Notably, the latter
patient, only 23 at the time, was profoundly disabled by the procedure and required institutionalization for the remainder of her life.
Even John Fulton, on whose original work the procedure was based,
acknowledged the potential benets, arguing that appropriate use
Figure 13. Original report by Freeman and Watts on their

experience with prefrontal lobotomies (Freeman W,
Watts JW. Bull N Y Acad Med 18:794-812, 1942).

of psychosurgery could save

American taxpayers $1 million per day, although he
was somewhat dismayed at
the manner in which Freeman performed the procedure, asking him at one
point, Why not use a shot
gun?(38). He also became
one of the most vocal proponents of more localized and
safer procedures speciFigure 14. The transorbital lobotomy
cally tailored to patients patechnique introduced by Amarro
thology. The widespread
Fiamberti and popularized by James
Watts and Walter Freeman (circa
and unregulated practice of
1940).
lobotomy makes it difcult
to assess the nature of patient outcomes, as negative
results were likely poorly
documented or unreported in many cases. One contemporary review
of outcomes in Great Britain reviewed 10,000 standard frontal lobotomy procedures performed between 1943 and 1954 (126). The authors found a 6% mortality rate, 1% incidence of seizures, and 1.5%
incidence of frontal lobe syndrome. A total of 70% of patients
reported some improvement, and 18% were able to return to a noninstitutional setting.
Pharmacology and the Demise of Psychosurgery
Although Freeman continued to champion and perform lobotomies
until the time of his death in 1972, the tide of public opinion had
already began to turn against him in the 1950s. An initially small but
growing body of criticism began appearing in the professional medical publications, including articles in the respected New England
Journal of Medicine and the American Journal of Psychiatry which expressed concern over the potentially underestimated risks of the
procedure (Figure 16) (57, 84). Within the realm of public opinion,
the increasing prevalence of the procedure meant a signicant portion of the American public came in contact with postlobotomized
individuals, increasing the awareness of the potential negative effects and consequences of the procedure.
As the antiestablishment cultural milieu of the 1960s and 1970s took
hold, the idea of the procedure being performed on institutionalized or
incapacitated patients with little attempt at informed consent sparked a
paranoia that was fueled by a number of popular written works and their
lm adaptations, including Tennessee Williams (whose sister underwent the procedure) play Suddenly Last Summer, in which an elderly
woman attempts to convince a neurosurgeon to perform a lobotomy on
her niece to prevent her from revealing an secret.
This was followed by the publication of Ken Keseys novel One Flew
Over the Cuckoos Nest in 1962, which depicted a boisterous patient at a
mental institution who was rendered nearly catatonic after the staff
tired of his instigations and gave him repeated electroconvulsive
shock treatments followed by a frontal lobotomy (Figure 17). The
book was followed by a lm adaptation that featured a remarkable
performance by Jack Nicholson as the protagonist and that swept
the Academy Awards when it was released in 1975 to much critical
and popular acclaim. Even more subversive views were presented in
controversial works such as the book Violence and the Brain, written in
1970 by the neurosurgeons Vernon Mark and Frank Ervin, which
postulated that psychosurgery would eventually be used by governments for widespread mind control. Public interest in the historical
practice of lobotomies persists, exemplied by more contemporary
popular works such as The Lobotomist by Jack El-Hai published in
2005, which chronicles the life and career of Walter Freeman, and
which subsequently formed the basis of a PBS documentary of the
same title.
The downfall of the initial era of psychosurgery came not from
public opinion, however, but from the compound 3-(2-chloro-10Hphenothiazin-10-yl)-N,N-dimethyl-propan-1-amine, the scientic
name for chlorpromazine, a phenothiazine derivative rst synthesized by the French pharmaceutical company Laboratoires RhnePoulenc and that initially was used as an adjunct to perioperative
sedation. The drug was released to the European market in 1953
under the trade name Largactil, a name derived from the broad
spectrum of activity and uses it was presumed to have (Figure 18).
The French surgeon Henri Laborit was the rst to perceive the potential use of the drug in psychiatric patients, and in 1952 it was
trialed in 38 psychotic patients at Hospital Sainte-Anne in Paris with
dramatic results, resulting not only in sedation but also improvements in cognition and psychotic symptoms.
The drug was licensed to Smith, Kline & French (now GlaxoSmithKline)
for use in the United States in 1953, and in 1955 the drug won approval
from the Food and Drug Administration for use in the treatment of
emesis under the trade name Thorazine. Thorazine revolutionized psychiatric care, and by 1953 more than two million psychiatric patients
had taken the medication, resulting in an explosion in the sales of
Smith, Kline & French and sparking rapid innovations in the eld of
psychopharmacology. The medication rapidly replaced insulin therapy,
electroconvulsive treatment, and psychosurgery in the treatment of institutionalized patients, and the inpatient psychiatric population in the
United States rapidly decreased in the decades that followed.
Despite the decline in the practice of psychosurgery, the controversy
persisted throughout the following decades, and a lasting connotation between psychosurgery and its
most notorious uses persisted.
This, together with revelations
arising from the Tuskegee
Syphilis Study, prompted the
United States Congress to pass
the National Research Act of
1974, which created the NationalCommissionfortheProtection
of Human Subjects of Biomedical
and Behavioral Research (42). Although the commission initially was intended to abolish
the psychosurgery altogether,
primarily instigated by the
outspoken critic of psychosurgery Peter Breggin, the physician experts who comprised it
Figure 15. An example of the WattsFreeman orbitoclast instruments,
found that psychosurgery
circa 1940 (Courtesy of Wellcome
could provide meaningful
Library, London).
benets to certain patients
S9

Figure 16. An early report by Jay Hoffman in 1949 raising concerns

regarding the safety and efficacy of prefrontal lobotomy.
with acceptable risks and should not be abolished outright. The Commission eventually produced the Belmont Report, a landmark guide to informed consent and the performance of medical procedures and medical
research, including on institutionalized or disadvantaged populations
(128).Theresultingmeaningfulreformstothepracticeofmedicalresearch
and the modern understanding of informed consent are one of the most
enduring legacies of the early era of psychosurgery.
THE MINIMALIST ERA OF PSYCHOSURGERY

The Advent of Minimalism
Despite the afrmative ndings of the Belmont Report, the social
and legal backlash against psychosurgery nevertheless caused a
precipitous decline in the practice of psychosurgery in the 1970s,
Figure 17. The first-edition covers of two contemporary works of fiction

that shaped the popular perception of psychosurgery and that were
subsequently made into films (circa 1960).
S10
Figure 18. Henri Laborit, the French surgeon instrumental in the

introduction of Largactil into psychiatric use in Europe, an early example
of the medication, and an advertisement for Thorazine in the United
States. Thorazine was the first antipsychotic introduced for clinical use,
and largely supplanted the surgical treatment of psychiatric illness (circa
1950s).
and the practice of psychosurgery remains limited to a small scale

at select centers internationally. Nonetheless, the practice of
psychosurgery lingered and was aided by a number of technological and technical evolutions that brought about a quiet renaissance in the safety, efcacy, and understanding of psychosurgery. These advances included the introduction of surgical
stereotaxy, the increasing minimalism and sophistication of neurosurgical procedures, technological innovations in neuroimaging, and the availability of stereotactic and noninvasive radioactive ablation (Table 2).
In terms of minimalism, even many of Freemans contemporaries
recognized the deciency of his approach and sought to achieve a
more selective ablation of pathologic areas of the brain. One such
contemporary was William Beecher Scoville, a neurosurgeon whose
training included experiences at Bellevue Hospital in New York, the
Massachusetts General Hospital, the Lahey Clinic, and the University Hospital in Baltimore (Figure 19). He ultimately became the
director of the Department of Neurosurgery at the Hartford Hospital, where he was afliated with Yale Medical School. Using the
understanding of neuroanatomic pathways at the time, he performed selective cortical undercutting procedures to separate presumptively abnormal cortex from underlying white matter tracts. He
is recognized for rst developing the technique of orbital undercutting but also targeted Brodmanns areas 9 and 10 as well as the
cingulate gyrus (Figure 20) (114). Although crude by modern standards, Scovilles efforts were the rst to implement the selective
destruction of abnormal tissue in a more anatomically localized
manner using technically sophisticated means, creating a new and
divergent concept of psychosurgery than that popularized by Moniz
and Freeman.

Table 2. Evolution of Minimalism and Precision in Psychosurgery: Tools and Concepts

Date
Event
1889
D. N. Zernov first uses a navigation system based on polar coordinates to drain a cerebral abscess
1908
Victor Horsley and Robert Clarke introduce the Horsley-Clarke stereotactic apparatus
1948
William Scoville introduces the concept of minimalism with the cortical undercutting approach
1948
Sir High Cairns performs first open cingulotomy
1949
Ernest Spiegel and Henry Wycis perform the first stereotactic dorsomedial thalamotomy using ventriculography
1949
Jean Talairach creates the concept of the anterior capsulotomy
1951
Lars Leksell proposes the concept of radiosurgery and further develops and popularizes the anterior capsulotomy
1958
Trent Wells and Ed Todd introduce the Todd-Wells stereotactic instrument
1958
First stereotactic radiosurgical procedure for psychiatric disease using proton beam radiation performed at the Gustaf Werner Institute in Sweden
1962
Eldon Foltz and Lowell White develop the stereotactic cingulotomy
1964
Geoffrey Knight introduces the subcaudate tractotomy
1967
Thomas Ballantine introduces thermal coagulation for stereotactic cingulotomy
1968
Lars Leksell introduces the first gamma knife prototype unit for stereotactic anterior capsulotomy, including use of the Leksell Stereotactic
System
1973
Desmond Kelly and Alan Richardson perform the first limbic leucotomy
1973
First EMI computed tomography scanner installed in the United States
1978
Russell Brown, Theodore Roberts and Trent Wells create practical concept of precise translation of imaging date to operative event
1983
Michael Apuzzo and Peter Heilbrun publish initial clinical experience with the image guided Brown Roberts Wells (BRW) Stereotactic System
1987
Eric Cosman co-creates refinement of image guided stereotaxis with the Cosman Roberts Wells (CRW) Stereotactic System
2007
Gamma Knife Perfexion radiosurgical device introduced
Stereotactic Neurosurgery
The most signicant innovation to propel the minimalist vision of
psychosurgery was the development of surgical stereotaxis. There
was a general feeling that the principles of psychosurgery were
sound but that smaller and more specic structures should be targeted to achieve optimal therapeutic benet while avoiding unnecessary morbidity and unwanted neurologic decits. Initial attempts
at stereotactic surgery began in the late 19th and early 20th century.
As early as 1889, D. N. Zernov, a Russian surgeon in Moscow, used a
navigation system (called an encephalometer) based in polar coordinates and referenced to external landmarks to drain a cerebral
abscess (66, 138). Sir Victor Horsley and Robert Clark of the University College London Hospital were credited with creating the rst
widely used stereotactic apparatus for use in animal experiments in
1908, known as the Horsley-Clarke apparatus (Figure 21) (24, 58).
The device could introduce a probe into subcortical structures dened in a Cartesian coordinate system of three orthogonal axes. This
was extended to human applications by Ernest Spiegel and Henry
Wycis, who introduced a Cartesian stereotactic system using x-ray
ventriculography in 1947 and in 1949 introduced the stereotactic
dorsomedial thalamotomy (Figure 22) (121). In addition to lesions in
the dorsomedial thalamic nucleus for treatment of agitation and
psychosis, Spiegel and Wycis also lesioned the medial thalamus for
epilepsy and mesencephalic pain pathways for intractable pain (99,
120). Electrode positioning in the apparatus of Spiegel and Wycis
was achieved by adjusting a sliding carrier along a base plate in the
anteroposterior and mediolateral axes, with vertical adjustments

made by a microdrive. Although they experienced little clinical success, their efforts represented the rst attempt to perform a minimally invasive subcortical ablative procedure.
In 1949, Lars Leksell of Sweden introduced an alternative stereotactic system that was easier to implement in the operative setting
(Figure 23) (80). His system consisted of a semicircular arc apparatus that allowed for introduction of an electrode or probe to a target
along any trajectory, as the target would lie in the center of the arc
(78). He intended to use the device for the stereotactic treatment of
psychiatric illness, and along with his contemporary Jean Talairach,
a French neurosurgeon who created the Talairach brain coordinate
system, is credited with the creation of the anterior capsulotomy
(Figure 24). A modied form of their procedure, the anterior capsulotomy, remains in limited use today for the treatment of refractory
psychiatric illness, with reported response rates as high as
60%70%.
In addition to those mentioned already, several other groups attempted to create clinically serviceable stereotactic systems. In the
United States, Trent Wells and Edwin Todd began developing a
separate system, the early Todd-Wells stereotactic system (Figure
25). Trent Wells was a biomedical engineer who left college to join
the Air Force during World War II, ying 55 missions as a ghter
pilot over Europe before returning to Los Angeles, establishing a
modest biomechanical instrument laboratory in his garage. He initially created miniature stereotactic devices for use in animal labora-
S11

tories before he went on to

make an acquaintance with
Todd, a neurosurgeon.
Wells aviation background
was evident in his development of a human surgical
stereotactic device with
Todd, as the nomenclature
of navigating three-dimensional space carried over
into the design of his stereotactic systems. Ed Todds
pedigree included work
with John Fulton at Yale,
and so he had an ongoing
interest in modication of
Figure 19. William Beecher Scoville,
cerebral function and minithe American neurosurgeon who
malism. Together, Todd
introduced the orbital undercutting
technique for producing a more focal
and Wells produced their
lesioning than the transorbital
prototypes largely out of the
technique of Freeman and Watts.
workshop in Trent Wells
garage. The system was
subsequently commercialized with Radionics through the facilitation of Bernard Cosman.
Along with the Leksell system, it was used globally for a variety of
functional surgeries throughout the 1960s and 1970s.
With the advent of computed tomography (CT) in the 1970s, it
became apparent that there was a need to create a system of ducials
for translation of three-dimensional CT data to the operating room.
Russell Brown, a medical student with a previous background in
mathematics, was studying at the University of Utah at the time
when he conceived a potential solution to this problem by using an
N conguration of radio-opaque rods. He approached Theodore
Roberts, then the chairman of neurosurgery at Utah, with his idea
(Figure 26). Roberts, together with Trent Wells, devised the practical
method for using this concept to correlate intracranial pathology or
anatomic landmarks identied on imaging to an external reference
system, allowing translation to the operating room. This renement
led to the development of the Brown-Roberts-Wells (BRW) Stereotactic System (Figure 27).
Michael Apuzzo at the University of Southern California and Peter
Heilbrun at the University of Utah initially used watermelon phantoms to rene the BRW system before performing and subsequently
reporting the rst extensive series of CT-guided stereotactic procedures with it (Figures 28 and 29) (8, 53). These clinical experiences
and subsequent technical renements led to enhanced interest in
and popularization of the methodology worldwide. Subsequent renements of the apparatus by Eric Cosman, a physicist at the Massachusetts Institute of Technology, with Trent Wells in the 1980s
resulted in the production of the last iteration of the device in the
Cosman-Roberts-Wells (CRW) stereotactic system (26, 27). These
devices, along with the Leksell systems, remain the foundational
instruments for precision stereotactic procedures to this day.
Radioablation and Radiosurgery
It was also recognized by Scoville and those that followed that the
instrument used for ablative psychosurgery was critical to its
S12
success. Although Scoville focused on renement of mechanical

instrumentation and technique, the truly transformational leap
forward was the introduction of radiosurgery into the practice of
psychosurgery, which permitted precise localization of ablation
difcult to reproduce by purely mechanical means. Before the
introduction of external stereotactic radiosurgical platforms, the
options for nonmechanical lesioning consisted of the stereotactic placement of radioactive material into the area of interest,
typically yttrium-90 rods. Radiofrequency ablation or thermocoagulation was also frequently used thereafter and offered significant advantages over radionucleotides, negating the need for
handling of radioactive material and allowing a more precise and
controlled lesioning effect. These stereotactic ablation procedures would ultimately offer an important transition into the
later introduction of stimulation and neuromodulatory techniques, as the electrodes used in localizing the treatments yielded
early insights into neuroelectrophysiology.
In the 1950s it became recognized within the eld of neurosurgery that high-energy proton beams could serve a purpose for
localized radiation to the intracranial space (74). In 1958, initiated by a concept of Lars Leksell, a group from Sweden led by the
physicists Kurt Liden and Borje Larsson, constructed a proton
beam instrument using a synchro-cyclotron source at the Gustaf
Figure 20. Images depicting the craniotomy and corticotomy sites for
Scovilles undercutting procedure (A), and the instruments used for the
procedure (B) (1949).

Figure 21. William Horsley and Robert Clarke, at

University College Hospital of London (A), and their
original Horsley-Clarke stereotactic apparatus (B), which
was the first stereotactic system developed in 1908.
(Courtesy of the UK Science Museum/Science &
Society Picture Library.)
Stereotactic Ablative Targets

Historical attempts to modulate or disrupt the aberrant circuitry of
psychiatric illness using the techniques elucidated previously have
included the subcaudate tractotomy, anterior cingulotomy, limbic
leucotomy, and anterior capsulotomy (Figure 32). Geoffrey Knight
rst introduced the subcaudate tractotomy for the treatment of
movement disorders in London in 1965 by using yttrium-90 rods
placed stereotactically into the substantia innominata (Figure 33) (69,
70). The rods were later replaced with radiofrequency thermocoagulation, with reasonable results in the treatment of depression and
obsessive-compulsive disorder, with clinical improvement in approximately one half of patients (44, 56).
Thomas Ballantine introduced the cingulotomy in 1967. He used
thermal coagulation and air ventriculography to make a stereotactic
lesion in the anterior cingulate (10). The lesion disrupted reciprocal
activity from the dorsal anterior cingulate to the orbitofrontal gyrus,
amygdale, and hippocampus via the cingulum bundle and remains one
of the most commonly reported procedures for surgical management
of obsessive-compulsive disorder (OCD) and depression. In the 1980s
he reported symptomatic improvement in the range of 25%50% (9).
Desmond Kelly and Alan Richardson introduced the limbic leucotomy in England in the 1970s, which consisted of ve distinct stereotactic lesions bilaterally in the lower medial frontal lobes and cingulum,
designed to interrupt the frontothalamic loop and the circuit of Papez,
and essentially combined the anatomic disruptions of a subcaudate
tractotomy and cingulotomy (68). In one series of 66 patients, they
reported signicant improvements in 89% of patients at 16 months
(94). As noted previously, the anterior capsulotomy was initially introduced by Talairach and popularized by Leksell, with a large series indicating that nearly one half of patients with OCD have at least a 33%
Werner Institute in Uppsala, Sweden (81, 82). The device was

cumbersome but was used initially for anterior capsulotomies
and other functional procedures (Figure 30). In 1968, a primordial prototype Gamma Unit using a ring of Cobalt-60 radioisotope sources was constructed at Sophiahemmet Hospital by
Leksell and the aforementioned group mentioned (75). Because
of limited contouring of the sources, the device was principally
used initially for functional neurosurgery with focal lesioning of
tracts or nuclei and produced sharply demarcated disk-shaped
lesions, although other lesions such as arteriovenous malformations were occasionally treated as well.
A second prototype using spherical radiation sources akin to the
modern iteration of the Gamma Knife was constructed at the Karolinska Hospital in Stockholm in 1974 (Figure 31) (79). Subsequent
renements of this prototype nally led to a commercially available
Gamma Knife unit in the mid 1980s, which was coupled with the
Leksell stereotactic and ducial system, enabling translation of CT
images into treatment plans (83). Once introduced, this technology
allowed the rst truly noninvasive stereotactic radiosurgical treatment of psychiatric disease. Subsequent generations of the Gamma
Knife platform are still used for noninvasive ablative treatment of
psychiatric disease, particularly for treatment-resistant obsessive
compulsive disorder and depression.
Figure 22. Ernest Spiegel, who along with Henry Wycis

developed a Cartesian stereotactic system using x-ray
ventriculography and used it to perform the first
stereotactic dorsomedial thalamotomy in 1949.
S13

improvement in symptoms
as determined by the YaleBrown obsessive-compulsive
scale (78, 98, 125). Adverse
effects for all of these procedures are similar, with lethargy, confusion, transient incontinence and personality
changes being the most commonly reported (41).
The Emerging Role of

Imaging in Psychosurgery
From its infancy, imaging
was foundational to the
Figure 23. Lars Leksell, the Swedish
practice of psychosurgery,
neurosurgeon who created the
and the progression of imstereotactic system shown, and
along with Jean Talaraich, was
aging technologies has both
instrumental in popularizing the
improved our understandanterior capsulotomy in 1949.
ing of the neurological pathways and anatomy involved in
psychiatric disease and allowed increasingly focused and sophisticated treatment of these pathways via the use of psychosurgery (Table 3). Watts and Freeman used
iodinated oils and plain radiographs of the skull to crudely identify the
location of their leucotomy tracts, which enabled them to create external anatomic correlates to enable somewhat-reproducible trajectories
for their leukotomes. The subsequent introduction of plain radiograph
ventriculography was the foundation for the creation of stereotactic
neurosurgery, and although it was imprecise by modern standards, it
was the rst imaging modality that allowed minimally invasive or noninvasive neurosurgical procedures via the use of xed intracranial landmarks. Although simple, this technology was largely responsible for
allowing the progression of psychosurgery from the globally ablative
frontal lobotomy to the more focused procedures that followed it.
Structural Imaging
The introduction of the rst EMI CT scanner in the early 1970s allowed
noninvasive imaging of patient-specic cerebral anatomy for the rst time. This
enabled renement of the
stereotactic treatment of psychiatric disease with improved localization of anatomic structures, particularly
with the subsequent introduction of the BRW and Leksell Stereotactic Systems and
other individual methods of
Figure 24. Jean Talairach, the French
stereotaxy that predated it.
neurosurgeon who developed a
Moreover, it enabled practicoordinate system that was
tioners to see the immediate
instrumental in the development of
surgical stereotaxis and is credited
anatomic results of ablation,
with initiating the anterior
as well as the delayed degencapsulotomy in the 1940s.
eration associated with abla-
S14
Figure 25. Edwin Todd (A), the America neurosurgeon, and Trent Wells
(B), the American biomedical engineer who together created the ToddWells Stereotactic System in the 1970s. Wells also co-created the
Brown Roberts Wells (BRW) and Cosman Roberts Wells (CRW) systems
that succeeded it, shown here with the base ring and arc of the BRW
system, circa 1980.
tive procedures, without the necessity of waiting for an autopsy to conrm the successful localization of the lesions. Of note, retrospective CT
imaging of patients who had undergone previous lobotomies clearly
demonstrated the heterogeneity and imprecision of the lesioning and
white matter deterioration that occurred after this procedure as it was
initially practiced, which conrmed the ndings of previous contemporaneous autopsy studies (61, 124).
The initial introduction of magnetic resonance imaging (MRI) a
decade later rened the level of anatomic detail available with noninvasive imaging, and thus the level of precision of stereotactic
procedures. However, the subsequent development of more sophisticated modes of MRI revolutionized the ability to noninvasively
localize not only anatomy
but function as well. The use
of traditional MRI allows
the postoperative assessment of lesion size and location, and moreover permits
the correlation of these parameters to therapeutic results and side effects. For instance, the presence of
perilesional edema on MRI
has been associated with the
development of fatigue and
loss of initiative after anterior capsulotomy or cingulotomy for OCD (93).
Diffusion tensor imaging
(DTI) is a type of diffusionFigure 26. Theodore Roberts, the
weighted MRI that assesses
American neurosurgeon who along
with Russell Brown and Trent Wells
the diffusibility of protons in
created the BRW Stereotactic
water along multiple axes, or
System in 1978.
tensors, and allows for a

Figure 27. An early prototype of the BRW Stereotactic System

demonstrating the base ring and arc (A), the base ring and localizer (B),
voxel by voxel assessment of the principle directions of diffusion

(Figure 34). Within axons, water diffusion is restricted by the axon wall
and myelin sheath, such that DTI can detect the average direction of
white matter tracts within each voxel, allowing the pinpoint localization
and the phantom base (C). (Courtesy of Springer Images.)
of pertinent white matter tracts before and after lesioning (65). Magnetization transfer imaging is another MRI-based technique that can detect areas of demyelination by differentiating between free and bound
protons, which are associated with free water in tissue and macromol-
S15

ecules, respectively, with the

latter including water bound
to myelin. This technique,
similar to DTI, can be used to
assess for the specic lesioning effect of stereotactic or radioablative procedures on
white matter tracts.
Functional Imaging
More dynamic imaging techniques have also permitted
imaging not only of anatomy,
but function as well. Functional MRI is sensitive to relative changes in oxyhemoglobin versus deoxyhemoglobin
Figure 28. Michael Apuzzo, the
within tissue and so can deAmerican neurosurgeon with one of
the early prototypes of the CRW
tect changes in metabolism
Stereotactic System. Along with
associated with activation of
Peter Heilbrun, Apuzzo was
specic areas of the brain,
responsible for much of the early
development, clinical testing, and
which allows for noninvasive
reports of the use of both the CRW
functional-anatomic correlasystem and its predecessor, the
tion and also for the identiBRW systems (circa 1990).
cation of areas of function
that are abnormal or altered
in diseased states. In this respect, positron-emission tomography (PET), single-proton emission
computed tomography, and magnetoencephalography all also play a
potential role both in identifying areas of functional aberration, and for
pretreatment and posttreatment comparisons for the assessment of the
modulatory effect of treatment. A more recent imaging innovation with
signicant ramications for the imaging of psychiatric illness is molecular imaging, which involves the use of molecules target to specic
transmitters or cellular receptors, and which modulate the imaging
signal, typically using MRI or
PET, to detect subtle variations in receptor concentrations or other biologic markers that could be indicative of
focal abnormalities associated with diseased states.
Future innovations in
neuroimaging, including
the use of nanoparticles for
improved anatomic and
functional resolution, with
the ability to detect precise
disturbances in anatomic,
metabolic, or neurotransmitter function, will likely
play an increasing role in
psychosurgery as our unFigure 29. Peter Heilbrun, the
derstanding of the aberrant
American neurosurgeon who
provided critical ideas and initiative
pathways involved psychiatduring the development of the BRW
ric illness improves, includStereotactic System (circa 1980).
ing the differentiation of
S16
Figure 30. A prototype proton beam stereotactic

radiosurgical device used for anterior capsulotomies at
the Gustaf Werner Institute in Sweden in 1960.
different subtypes of certain broad diagnoses which may require

divergent forms of treatment (134). Neuroimaging may eventually
dene the specic aberrant pathways associated with psychiatric
illness and therefore dene regions appropriate for therapeutic targeting. This type of imaging will also augment the necessarily subjective nature of the psychiatric diagnosis and stratication, and
enable better selection of those patients suitable for intervention.
THE NEUROMODULATORY ERA OF PSYCHOSURGERY

The aforementioned constellation of advances in the latter half of the
20th century set the stage for a conceptual breakthrough in the surgical
treatment of psychiatric illness in the late 1990s with advent of the rst
Figure 31. The first functional gamma knife prototype using a spherical
arrangement of Cobalt-60 radio-isotope sources at the Karolinska
Hospital in Sweden in 1974.

lation to control neurologic disease, with reference to psychiatric disease in particular.

As a reection of the largely
unregulated nature of medical
investigation at the time, these
early efforts were dealt a setback by the unscrupulous use
of implanted electrodes for the
treatment of psychiatric disease
by the psychiatrist Robert
Heath at Tulane University in
the 1950s and 1960s. Heath
Figure 32. Localization of common selective ablation targets in the treatment of OCD, including anterior capsulotomy
used inconsistent clinical crite(A), cingulotomy (B), and subcaudate tractotomy (C) (54).
ria and unusual target localization with poor adherence to basic standards of scientic
research and was widely critinonablative, nondestructive treatment modality with the ultimate introcized for his efforts at the time; subsequently he met with little clinical
duction of deep-brain stimulation (DBS) to the eld (Table 4).
success (11, 16). However, his work with stimulation of the cerebellar
The concept of electrical stimulation of the human cerebrum is not a
vermis was notable for targeting a neural network or pathway as opnew onein fact, it is not even a creation of the 20th century. The
posed to a specic anatomic focus.
physician to the Roman emperor Claudius, Scribonius Largo, wrote in
Building on the work of a number of his contemporaries, who used
46 AD in his work Compositiones medicamentorum that the applimeasuring electrodes during stereotactic positioning of thermoablative
cation of the species Torpedo nobiliani, or the electric ray, to the human
procedures, in 1952 the Spanish neuroscientist, Jose Delgado, was the rst
cranium could serve as a remedy for headache (119). Up until the 18th
to describe the implantation of intracranial electrodes in humans. He subcentury, external electrical stimulation with electric rays or eels was
sequently implanted his stimoceivers in various animals and even huused in the treatment of pain, depression and seizures (67). In 1804,
mans in an attempt to demonstrate the ability to modulate or control the
Giovanni Aldini, a professor of physics at the University of Bologna,
mind, although he met with limited success.
conducted experiments involving the electrical cortical stimulation of
freshly decapitated human prisoners, and found that stimulation resulted in distortion and grimacing of the subjects facial features (1). In
Peripheral Stimulation
1809, Luigi Rolando, an Italian anatomist, rst demonstrated that elecContemporaneously, a number of individuals were exploring the
trical impulses could modify the function of brain regions (33, 107).
effects of peripheral stimulation on neurologic and cerebral funcThis laid the foundation for the subsequent centuries of neurophysiotion. In 1965, Ronald Melzack and Patrick Wall proposed a theory of
logic studies of neuronal function, and also opened up the possibility of
pain termed the gate control theory, based on peripheral nerve
a therapeutic effect of direct cerebral electrical stimulation. The latter
stimulation. They posited that increased stimulation of large-diamwould not come to fruition until the middle of the 20th century, when a
eter A bers relative to thin c bers caused gating of the signal in
number of investigators began to explore the potential of brain stimuthe dorsal horn of the spinal cord, resulting in a diminished sensory
awareness of the painful stimuli (91). Although this theory of pain
has subsequently undergone numerous revisions and renements,
it formed the basis of much of the subsequent work in both peripheral and central neural stimulation.
Another frontier in peripheral stimulation predating Melzack and
Wall was that of vagal stimulation. Although the vagus nerve has
numerous efferent functions, studies have demonstrated that the
nerve may be constituted of as much as 80% afferent bers with
broad projections to the supratentorial brain via the nucleus of the
solitary tract. As early as 1883, James Corning proposed the use of
vagal nerve stimulation as a means of central modulation. This was
followed by work by Bailey and Bremner in the 1930s, in which they
demonstrated electroencephalographic changes with vagal stimulation (47). In 1988, J. Kifn Penry and Christine Dean demonstrated
the rst successful use of vagal nerve stimulation for the treatment of
drug-resistant epilepsy in humans in a small group of patients,
Figure 33. Images from Geoffrey Knights paper describing the subcaudate
ultimately leading to its approval by the Food and Drug Administratractotomy, including the McCaul stereotactic device he used (A) and a
tion for this purpose. Later, Arun Amar, Christopher DeGiorgio, and
radiograph demonstrating the typical trajectory (B) (1965) (69).
Michael Apuzzo described the surgical techniques and outcomes for
S17

Table 3. Radiographic Advances in Psychosurgery

Modality
Advance
Plain radiographs
Localization of leucotomy tracts and establishment of surgical landmarks
Ventriculography
Early stereotactic systems and surgical minimalism
Computed tomography
Three dimensional anatomic resolution with improved stereotactic localization and immediate confirmation of lesion volumes
Magnetic resonance imaging (MRI)
Improved tissue resolution and localization of stereotactic or minimally invasive ablation
Diffusion tensor imaging (DTI)
Noninvasive evaluation of the integrity of white matter tracts
Functional MRI (fMRI)
Noninvasive functional anatomic correlation in diseased states
Positron emission tomography (PET)
Assessment of abnormal metabolic states potentially correlated with diseased states
Magnetic encephalography (MEG)
Noninvasive derivation of intracranial electrical activity
High-Tesla MRI
Increased spatial and temporal resolution of MRI
Molecular imaging
Imaging of specific molecules, transmitters or receptors to assess focal biological processes involved in psychiatric
derangements or alterations of mental function
Emerging imaging techniques
Increasing resolution, in combination with nanoparticles or neurotransmitter level noninvasive imaging to assess and
correlate focal aberrations in cerebral function
vagal nerve stimulation in an extended series of patients with intractable epilepsy at a single institution (3).
It was soon recognized during the initial clinical trials that many
patients receiving vagal nerve stimulation for epilepsy experienced a
concomitant improvement in mood. One study by Elger et al (29)
found that this effect was observed independent of improvement in
seizure frequency, indicating that it was not merely a result of successful treatment of the patients primary disease. This observation
was commensurate with known anatomic projections from the nucleus of the solitary tract and locus ceruleus to a number of limbic
targets involved in mood regulation and which demonstrate
changes associated with current anti-depressant pharmacotherapy
(15, 55). This led to subsequent studies of vagal nerve stimulation
exclusively for mood disorders in the absence of a seizure disorder,
including work by Rush et al. (109, 110) and George et al. (43).
Deep Brain Stimulation
In 1960, Hassler et al. (52) found during stereotactic exploration
of the basal nuclei for pallidotomy that low-frequency stimulation could worsen tremor and high-frequency stimulation could
ameliorate it. This nding was rst implemented in practice in
1967 by Bechtereva et al. (12) with chronic DBS of the thalamus,
striatum, and pallidum for the treatment of movement disorders,
but it was not until the 1970s and 1980s that the modern concept
of implanted chronic stimulation was introduced. Efforts in the
1970s included stimulation of the ventral posteromedial nucleus
thalamus for control of facial anesthesia dolorosa after rhizotomy for trigeminal neuralgia in 1973 reported by Hosobuchi et al.
(59), and stimulation of ventral periaqueductal gray in the midbrain for treatment of oncologic pain reported by Richardson and
Akil in 1977 (108). In the 1980s, numerous groups began to report
the use of chronic DBS for the management of movement disorders, including Brice and McLellan (20), Blond and Siegfried
(17), Siegfried and Shulman (117), and Benabid et al. (13, 14)
(Figure 35). As a result of these studies and others, DBS was rst
S18
approved for human use in essential tremor by the Food and Drug
Administration in 1987 (Figure 36).
Neuromodulation in Neuropsychiatric Disorders

After the initial approval for DBS in movement disorders, interest
was immediately likewise directed towards possible uses in additional neuropsychiatric diseases, including dystonia, depression,
OCD, and even obesity, and the management of these disorders
remain an exciting frontier in DBS. Initial observations of early
patients with subthalamic nucleus deep brain stimulation indicated
that there was some psychomodulatory effect, as the patients had
occasional affective changes after the procedure. Since that time, the
disorders with the most established safety and efcacy of treatment
with DBS are OCD and major depressive disorder (MDD). OCD and
MDD are now considered disorders of brain networks rather than
shortages or overabundances of specic neurotransmitters. Attempts to modulate these networks have been the goal of surgical
treatment of refractory cases, with an accumulated 15 years of experience in the treatment of OCD to date, with more recent strides in
the use of DBS for MDD. Preliminary results suggest that DBS will
become a mainstay in the management of these and other treatmentresistant neuropsychiatric disorders in the near future.
Obsessive Compulsive Disorder

OCD is a disorder characterized by intrusive thoughts (obsessions)
and repetitive behaviors (compulsions) that signicantly impact the
lives of patients affected by the disorder. The obsessions and compulsions become impairing and time-consuming, leading patients
to go to great lengths to avoid situations that provoke them. The
behaviors are noxious to the patients and are deleterious to their
social, scholastic, and occupational functions. In Western countries
the prevalence of OCD is estimated to be 2% of the population, and is
typically initially managed with pharmacotherapy and cognitive be-

center study of eight patients with OCD demonstrated signicant

improvement in 75% of patients (45). Hypomania was reported as
an adverse event as was relapse of OCD symptoms with battery
failure. Subthalamic nucleus stimulation has been attempted as
well, and a 10-month, double-blind, crossover study published in
2008 demonstrated a mean reduction of symptoms of approximately 32 percent with active stimulation (87).
Figure 34. DTI tractography demonstrating the white matter tracts of the
whole brain and brain stem, including the tracts of the limbic system.
havioral therapy (104). Pharmacotherapy is usually successful, but

nonetheless approximately 7% of patients remain refractory to treatment (137).
Initial experiences of DBS effects on OCD included a report by
Mallet et al. (87) in 2008 noting a signicant (80%) reduction in the
Yale-Brown obsessive-compulsive scale scores in two patients with
Parkinson disease and OCD. The electrodes in these cases were
placed more medial and anterior in the subthalamic nucleus than
anticipated. A group originating in Belgium and Sweden including
Bart Nuttin, Paul Cosyns, and Hilde Demeulemeester published
several series of cases involving the implantation of multicontact
electrodes into the internal capsule for patients with OCD, with the
distal electrode in the nucleus accumbens, with efcacy similar to
that of an anterior capsulotomy (Figure 37) (40, 97).
A group from Germany modied the target selection to the shell
of the nucleus accumbens, a region chosen for its proximity to the
ventral internal capsule and projections to the amygdale, dorsomedial thalamus, and prefrontal and orbitofrontal cortex, which have
been implicated in the pathogenesis of OCD. Of the patients with
successful placement of the electrode, all three had near complete
resolution of their symptoms (6). A three year-follow up of a multi-
Major Depressive Disorder

MDD is a highly prevalent and debilitating psychiatric disorder, as
noted previously. Primary medical treatment typically consists of
selective serotonin reuptake inhibitors, whereas other second-line
agents include monoamine oxidase inhibitors, tricyclic antidepressants, and dual serotonin and norepinephrine reuptake inhibitors.
Despite the variety of treatments available, as many as one third of
patients do not respond to medical therapy.
As in OCD, DBS provides an attractive alternative to traditional
lesioning procedures because of its nondestructive, reversible nature. Efforts by Helen Mayberg and Andres Lozano have met with
some success (Figure 38). Lozano based his target location on the
nding that changes in metabolism on PET in the subgenual cingulate
cortex were associated with successful response to antidepressant pharmacotherapy. After implanting electrodes to this area, four of six trial
patients with major depression went into remission, with greater than
50% reduction in their Hamilton Depression Rating Scales scores (90).
This was followed by a larger study conducted by Mayberg and Lozano
of 20 patients based out of Toronto, with roughly two thirds of patient
demonstrating improvement of MDD symptoms, and 35%having complete resolution of their disease (85).
Other promising targets for treatment of MDD include stimulation of the anterolateral internal capsule. In a study by Greenberg et
al. (45) of patients with depressive symptoms and comorbid OCD,
half of the eight patients with MDD experienced improvement in
mood and affect with stimulation of this area. The ventral striatum
and nucleus accumbens may also prove to be valuable targets. The
nucleus accumbens projects to the limbic brain areas including the
SCC, stimulation of which could have expanding indications beyond
MDD in the management of addiction and disorders of brain reward
circuitry. A recent study of 15 patients with stimulation of the ventral
capsule/ventral striatum by Malone et al. (88) demonstrated a 50%
responder rate and 20% remission rate.
Tourette Syndrome
The inherent ability of DBS to modulate neurobehavioral circuitry
has opened the door for treatment of a number of otherwise-intractable disorders beyond OCD and MDD. Tourette syndrome is characterized by chronic vocal and motor tics with typical onset in early
school age and often is comorbid with attention-decit hyperactivity
disorder or OCD. Tourette syndrome is thought to affect anywhere
between 0.7% and 4.2% of individuals, although symptom severity
typically lessens in adulthood (63). Vocal tics include coughing,
clearing ones throat, and coprolalia. Motor tics include blinking,
grimacing, snapping, or movements of the face. These movements
or gestures tend to resemble coordinated or repetitive fragments of
normal behaviors. Tics are exacerbated by stress, fatigue, boredom,
S19

Table 4. The Evolution of Neuromodulation

Date
Event
46 AD
Roman physician Scribonius Largo publishes Compositones medicamentorum, which mentions use of the electric ray as a means of treating headache
1804
Giovanni Aldini demonstrates control of human facial expression via direct cortical stimulation
1883
James Corning proposes use of vagal nerve stimulation for central nervous system modulation
1938
Percival Bailey and Frdric Bremer demonstrate electroencephalographic changes with vagal nerve stimulation
1952
Jose Delgado implants intracranial electrodes or stimoceivers in humans
1960
Robert Heath attempts vermian stimulation for control of psychiatric disease
1965
Ronald Melzack and Patrick Wall propose the gate control theory of pain with peripheral stimulation
1987
Alim-Louis Benabid uses implanted electrodes for the treatment of Parkinsonian tremor in humans
1988
Kiffin Penry and Christine Dean implant a vagal nerve stimulator for control of treatment-resistant epilepsy in humans
1997
The United States Food and Drug Administration approves DBS for the treatment of essential tremor
1998
Arun Amar, Christopher DeGiorgio and Michael Apuzzo publish detailed technical description and outcomes of vagus nerve stimulation for intractable
epilepsy
1999
Bart Nuttin, Paul Cosyns and Hilde Demeulemeester publish series of deep brain stimulation to internal capsule for obsessive compulsive disorder
1999
Veerle Vandewalle publishes series of Gilles de la Tourette syndrome patients treated with thalamic DBS
2000
Christian Elger and John Rush demonstrate improvement in depressive symptoms with VNS
2005
Helen Mayberg and Andres Lozano report series of patients with DBS for treatment-resistant depression
2007
Schiff et al publish report of increased cognitive activity in a minimally conscious traumatic brain injury patient after thalamic DBS
DBS, deep-brain stimulation; VNS, vagus nerve stimulation.
and are often present during sleep. Because of the nature of tics, they
can be disabling from a social, occupational, and overall functioning
standpoint if they do not abate in adulthood. A report by Veerle
Vandewalle and subsequent groups indicate that both thalamic
stimulation and stimulation of the globus pallidus pars interna have
been effective in the reduction of tics (35, 86, 115, 132).
Addiction and Eating Disorders
Dysfunction in the reward circuitry underlying eating disorders and
addiction is quickly becoming a target for DBS as well.
More than 30 years ago,
Quaade et al. (103) stereotactically electrocoagulated
portions of the lateral hypothalamus
and
safely
achieved some weight reduction in three patients.
Furthermore, animal studies have identied the lateral
hypothalamus, ventromedial hypothalamus, and nucleus accumbens (NAc) as
potential targets for managing obesity (48). The NAc
Figure 35. Alim-Louis Benabid, the
French neurosurgeon who
overlaps with the circuitry of
contributed to the introduction of
the lateral hypothalamus
DBS for Parkinsonian tremor in 1987.
and may be involved in food
S20
reward circuitry. The central role of the NAc in reward circuitry also
makes it an attractive target in treating addiction.
Studies in rats suggest that DBS of the NAc may ameliorate cocaine addiction (131). Preliminary studies in humans undergoing
DBS of the NAc for other disorders (including Tourette and OCD)
indicate that smoking cessation may be aided with NAc stimulation
(71). A group from the Netherlands recently reported NAc stimulation in a single patient leading to both smoking cessation and
weight loss (89). DBS of the bilateral nucleus accumbens has also
been reported to reduce alcohol dependency in a patient undergoing
the procedure for an anxiety disorder (72). With regard to eating
Figure 36. An example of a production model of a type

of electrode array and pulse generator currently used
for DBS. (Courtesy of Medtronic.)

disorders, some early results suggest DBS may be effective in the management
of anorexia nervosa as well
(62, 123).
Posttraumatic Stress
Disorder
Posttraumatic stress disorder (PTSD) is another
pathologic entity associated
with alterations in the frontostriatal circuitry (18).
Figure 37. Bart Nuttin, the Belgian
neurosurgeon who described the use
PTSD is characterized by a
of capsular stimulation for the
response to a traumatic
treatment of treatment-resistant
event that involves recurOCD.
rent, intrusive recollections
of the event, avoidance of
stimuli associated with
trauma or generalized emotional numbing, symptoms of hyperarousal, and functional distress or impairment in social, occupational, or other important areas (4). Lifetime prevalence of PTSD is
estimated at 5%8% of men and 10%14% of women, making it
the fourth most common psychiatric disorder (19, 136). The NAc,
amygdala, and ventromedial prefrontal cortex are most commonly
shown to have alterations in function in patients with PTSD versus
healthy controls (92, 105, 116). This makes neuromodulation of the
frontostriatal circuitry or amygdala a potential option in the management of PTSD. thus far, animal studies suggest that high-frequency stimulation of the amygdala may alleviate symptoms of
PTSD (73).
Modulation of the Conscious State

Stimulation and neuromodulation in the context of movement disorders represented an important early step in the development of
neuromodulation of the brain, by using well-dened motor pathways for the extinction of modulation of disorders of motor function. Early efforts in the treatment of psychiatric disease, including
OCD, major depression, and Tourette syndrome, demonstrate the
difculty of treating more complex disorders of the mind wherein
the underlying neuroanatomic aberrancies are not as well elucidated. As the specic pathways and sites of dysfunction become
dened, perhaps using more targeted neuroimaging to dene these
regions, the efcacy of these methods should improve. Beyond these
efforts, however, the nal frontier of neuromodulation lies in the
alteration or augmentation of the mind and conscious state itself
(Table 5).
A group from Cornell led by Schiff et al. (113) demonstrated
signicant improvement in level of cognitive function in a 38-yearold patient who had remained in a minimally conscious state after
bilateral DBS of the central thalamus. The patient had a severe traumatic brain injury leading to the inability to communicate or follow
commands consistently for more than six years after his injury, with
MRI demonstrating thalamic and midbrain injury with preservation
of bihemispheric language networks. Bilateral DBS were targeted to
the anterior interlaminar thalamic nuclei and paralaminar re-
Figure 38. Helen Mayberg (A), the American neurologist, and Andres
Lozano (B), the Canadian neurosurgeon who described the placement of
DBS electrodes in the subgenual cingulate cortex for treatment of major
depression.
gions of the association nuclei because these regions had maximal concentrations of calbindin-positive neurons that have projections to supragranular cortical regions that are believed to play
a role in arousal. The patient had signicant improvements in
arousal, limb control, and oral feeding in the DBS on versus off
state.
However, results in larger trials have been mixed. For example, in
1990 Medtronic initiated a trial for implantation of DBS into patients
in a vegetative state, in which patients received bilateral centromedian thalamus or cervical spinal cord dorsal columns DBS. Although
some centers reported signicant functional improvement, this
nding was not consistent (25, 60, 127, 135). One reason for the
mixed results may be attributable to the heterogeneity of the patients
enrolled, in that patients with widespread cortical or subcortical
damage may have less potential for recovery than patients with intact
networks and isolated decits of central arousal (112).
In addition to consciousness, DBS may nd a role in the near
future in the management of dementias or other functional cognitive
disorders. The group of Lozano reported on a patient who, during
stimulation of the hypothalamus for obesity, began having autobiographical memories (49). This nding led to an initial phase I trial
evaluating forniceal/hypothalamic DBS in the treatment of Alzheimer disease. The study suggested potential slowing of cognitive
decline in the study cohort, opening the door to more research in
this realm (76).
THE FUTURE OF PSYCHOSURGERY

The neurosurgical contribution to the treatment and management of psychiatric disease presents great promise but also signicant challenges. The connotations associated with psychosurgery have signicantly limited its practice, but the increased
safety of medical practice and the social demand for more innovative solutions to medical and epidemiologic problems has created an environment in which the modern iteration of psychosurgery can nd traction. The increasing societal and ethical
S21

Table 5. Intractable Disorders Potentially Ameliorated by

Deep-Brain Stimulation Methods in Human or Animal Studies
Target
Major depressive disorder
Obsessive compulsive disorder
Tourette syndrome
Obesity
Addictions (nicotine, cocaine)
Alcoholism
Anorexia nervosa
Posttraumatic stress disorder
Alzheimer disease and dementias
Disorders of consciousness or persistent vegetative state
Cognitive dysfunction
acceptance of the invasive treatment of debilitating or disabling

psychological or physical states previously exclusively treated by
medical or behavioral means is clearly evident in the exponential
rise of bariatric surgery in the management of obesity. Modern
nonablative neuromodulatory techniques, and their future renements or as yet-undiscovered replacements hold the promise
of altering abnormal pathways with minimal alteration of normal
function, increasing the safety and social acceptability of these
treatments.
In introducing psychosurgery into a wider paradigm, it is useful to draw historical lessons from the development of the surgical management of epilepsy, which as it is now practiced in
centers such as ours consists of a multidisciplinary approach to
every patient with epilepsy, involving neurologists, neurosurgeons, and radiologists, with patients with intractable epilepsy
carefully screened with the use of clinical and radiographic criteria, including the use of MR and functional imaging and invasive
Wada testing to differentiate the anatomically and functionally
appropriate approaches to an individual patients disease process. Some have argued that it was the absence of this multidis-
ciplinary approach that initially led to the excesses of Walter

Freeman and his contemporaries (34).
One of the challenges of psychosurgery is that neurosurgeons
currently have minimal exposure to the diagnosis or management of psychiatric illness during their training, and the neurosurgical trainees experience is often limited to his or her brief
tenure on a psychiatric service as a medical student, with little
reinforcement thereafter. This is compounded by the fact that
psychiatry has a lexicon entirely distinct from routine neurosurgical practice, such that effective treatment of psychiatric disease
and effective collaboration with psychiatric practitioners will require a re-introduction of psychiatric discourse into routine neurosurgical training (46).
As opposed to epilepsy, which has been delineated into specic
electroencephalographic and clinical subtypes and can be localized
by the use of various noninvasive and invasive techniques to specic
anatomic origins, the anatomic substrates of psychiatric disease are
still not well understood. In addition, psychiatric illness has historically been categorized descriptively according to symptom clustering, with the original introduction of the Diagnostic and Statistical
Manual of Mental Disorders (DSM) in 1952 marking a signicant transition towards more standardized diagnostic categories. The DSM
has made it feasible to conduct standardized pharmacologic testing
for treatment of psychiatric illness, but it is probable that the diagnostic categories of the DSM as it currently exists do not have the
renement to guide surgical intervention, as the major diagnoses
dened by the DSM likely each result from multiple different neuroanatomic correlates. The ability to differentiate these different subtypes, whether clinically or based on current or future functional or
metabolic imaging, is essential to selecting appropriate beneciaries of surgical intervention.
Future frontiers include not only the renement of existing methods of stimulation techniques and improved machinebrain interfacing but also the possibility of other forms of neural modulation
(Table 6). This type of renement of scale and technique is exemplied by a recent publication in Science of the selective erasure of a fear
memory in rodents using diphtheria-toxin mediated ablation of a
small population of lateral amygdala neurons with increased levels
of a particular cell-signaling protein (50).
Drawing again on the correlation with epilepsy, efforts within our
own department have included the construction of implanted elec-
Table 6. Emerging and Future Technologies in the Surgery of the Mind

Technology
Application
Single electrode deep brain stimulation
Focal modulation of areas of aberrant function
Multi electrode arrays
Multi nodal stimulation or modulation based on real-time neuronal signal processing or biometric feedback
Local drug delivery
Local delivery of modulatory neurotransmitters or other molecules to selectively alter abnormal areas of function while
avoiding the systemic effects of psychotropic medication using local infusions or nanopolymers for regulated release
Gene therapy
Permanent alteration of neuronal function in global or targeted regions of interest
Stem cells transplantation
Restoration of neuronal function in disease states associated with hypoactive function
Molecular imaging
Noninvasive imaging at the molecular level of aberrations in receptors or molecules responsible for psychiatric disease
Nanotechnology
Increased resolution of imaging and intervention from the global lobectomy scale to the molecular and atomic level
S22

trode arrays for the detection and interdiction of epileptic seizure

activity, with real-time acquisition of neuronal ring and signal
processing with selective patterns of responsive stimulation, which
could eventually be adapted and applied to psychiatric illness once
the abnormal patterns of neurologic function are better understood.
Other future modalities include targeted drug delivery using targeted nanomolecules or invasive local delivery methods such as
REFERENCES
convection enhanced delivery, selective modulation of neurotransmitter release via targeted gene therapy, the restoration of function
with stem cell transplantation or induction, and various as yet-unknown techniques using a correlation of precise imaging and increasingly microscopic, even molecular or nanoscale interventions
to target the pathologic neuronal function responsible for the spectrum of intractable psychiatric illness.
ment of some chronic diseases. Conn Neurol

37:136-40, 1975.
1. Aldini J: Essai thorique et exprimental sur le galvanisme, avec une srie dexpriences faites devant
des commissaires de lInstitut nationale de France,
et en divers amphithtres anatomiques de Londres [in French]. Paris: Fournier Fils; 1804.
13. Benabid AL, Pollak P, Gross C: Acute and longterm effects of subthalamic nucleus stimulation in
Parkinsons disease. Stereotact Funct Neurosurg
62:76-84, 1994.
2. Alt KW, Jeunesse C, Buitrago-Tellez CH, Wachter

R, Boes E, Pichler SL: Evidence for stone age cranial surgery. Nature 387:360, 1997.
14. Benabid AL, Pollak P, Hommel M, Gaio JM, de

Rougemont J, Perret J: Treatment of Parkinson
tremor by chronic stimulation of the ventral intermediate nucleus of the thalamus [in French]. Rev
Neurol (Paris) 145:320-3, 1989.
3. Amar AP, Heck CN, Levy ML, Smith T, DeGiorgio

CM, Oviedo S, Apuzzo ML: An institutional experience with cervical vagus nerve trunk stimulation
for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery 43:1265-1276,
1998.
15. Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, Slater J: Effects of vagus
nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures.
Epilepsy Res 20:221-227, 1995.
25. Cohadon F, Richer E: Deep cerebral stimulation in

patients with post-traumatic vegetative state. 25
cases [in French]. Neurochirurgie 39:281-292,
1993.
26. Cosman ER, Wells TH Jr.: Combined use of a new
target-centered arc system with the BRW oor
stand and phantom base for a wider range of approaches and applications in stereotaxy of the head
and neck. Appl Neurophysiol 50:119-126, 1987.
27. Couldwell WT, Apuzzo ML: Initial experience related to the use of the Cosman-Roberts-Wells stereotactic instrument. Technical note. J Neurosurg
72:145-148, 1990.
28. Deutsch A: The Mentally Ill in America. New York:
Doubleday; 1937:452-460.
4. American Psychiatric Association: Task Force on

DSM-IV. Diagnostic and Statistical Manual of
Mental Disorders: DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.
16. Bishop MP, Elder ST, Heath RG: Intracranial selfstimulation in man. Science 140:394-396, 1963.
29. Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE:

Vagus nerve stimulation is associated with mood
improvements in epilepsy patients. Epilepsy Res
42:203-210, 2000.
5. Andlin-Sobocki P, Jnsson B, Wittchen H, Olesen

J: Cost of disorders of the brain in Europe. Euro J
Neurol 12(Suppl 1):1-27, 2005.
17. Blond S, Siegfried J: Thalamic stimulation for the

treatment of tremor and other movement disorders. Acta Neurochir Suppl (Wien) 52:109-111,
1991.
30. Fava M, Davidson KG: Denition and epidemiology of treatment-resistant depression. Psychiatric
Clin North Am 19:179-200, 1996.
6. Aouizerate B, Martin-Guehl C, Cuny E, Guehl D,

Amieva H, Benazzouz A, Fabriqoule C, Bloulac B,
Tignol J, Burbaud P: Deep brain stimulation for
OCD and major depression. Am J Psychiatry 162:
2192, 2005.
7. Apuzzo ML, Liu CY, Sullivan D, Faccio RA. Surgery
of the human cerebruma collective modernity.
Neurosurgery 61(Suppl 1):28, 2007.
8. Apuzzo ML, Sabshin JK: Computed tomographic
guidance stereotaxis in the management of intracranial mass lesions. Neurosurgery 12:277-285,
1983.
9. Ballantine HT Jr., Bouckoms AJ, Thomas EK, Giriunas IE: Treatment of psychiatric illness by stereotactic cingulotomy. Biol Psychiatry 22:807-819,
1987.
10. Ballantine HT Jr., Cassidy WL, Flanagan NB, Marino R Jr.: Stereotaxic anterior cingulotomy for
neuropsychiatric illness and intractable pain. J
Neurosurg 26:488-495, 1967.
11. Baumeister AA: The Tulane electrical brain stimulation program. A historical case study in medical
ethics. J Hist Neurosci 9:262-278, 2000.
12. Bechtereva NP, Bondartchuk AN, Smirnov VM,
Meliutcheva LA, Shandurina AN: Method of electrostimulation of the deep brain structures in treat-
18. Breslau N: Outcomes of posttraumatic stress disorder. J Clin Psychiatry 62(Suppl 17):55-59, 2001.
19. Breslau N, Davis GC, Andreski P, Peterson E: Traumatic events and posttraumatic stress disorder in
an urban population of young adults. Arch Gen
Psychiatry 48:216-222, 1991.
20. Brice J, McLellan L: Suppression of intention
tremor by contingent deep-brain stimulation. Lancet 1(8180):1221-1222, 1980.
21. Brickner RM: An interpretation of function based
upon a case of bilateral frontal lobectomy. Proc
Assoc Res Nerv Ment Dis 13:259-351, 1932.
22. Broca P: Sur le sige de la facult du langage articul [in French]. Bull Soc Anthropol 6:377-393,
1865.
ber Rindenexcisionen, als Beitrag
23. Burckhardt G: U
zur operativen Therapie der Psychosen [in German]. Allg Zeschr f Psychiatr 47:463-548, 18901891.
24. Clarke RH, Horsley V: THE CLASSIC: on a method
of investigating the deep ganglia and tracts of the
central nervous system (cerebellum). Br Med J
1906:1799-1800. Clin Orthop Relat Res 463:3-6,
2007.
31. Feldman R, Goodrich J: Psychosurgery: a historical

overview. Neurosurgery 48:647-659, 2001.
32. Ferrier D: The Functions of the Brain. London:
Smith, Elder & Co.; 1876.
33. Finger S: Origins of Neuroscience: A History of
Explorations into Brain Function. New York: Oxford University Press; 1994.
34. Fins JJ, Rezai AR, Greenberg BD: Psychosurgery:
avoiding an ethical redux while advancing a therapeutic future. Neurosurgery 59:713-716, 2006.
35. Flaherty AW, Williams ZM, Amirnovin R: Deep
brain stimulation of the anterior internal capsule
for the treatment of Tourette syndrome: technical
case report. Neurosurgery 57(Suppl 4):E403,
2005.
36. Freeman W, Watts J: Psychosurgery: In the Treatment of Mental Disorders and Intractable Pain.
2nd ed. Springeld: Charles C Thomas; 1950.
37. Fritsch G, Hitzig E: Uber die elektrische Erregbarkeit des Grosshirns [in German]. Arch Anat
Physiol 37:300-332, 1870.
38. Fulton JF: Frontal Lobotomy and Affective Behaviour: A Neurophysiological Analysis. New York:
W. W. Norton; 1951.
S23

39. Fulton JF, Jacobsen CF: The functions of the frontal lobes: A comparative study in monkeys, chimpanzees, and man. London: Abstracts of the Second International Neurological Congress; 1935:
70-71.
40. Gabriels L, Cosyns P, Nuttin B, Demeulemeester
H, Gybels J: Deep brain stimulation for treatmentrefractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in
three cases. Acta Psychiatr Scand 107:275-282,
2003.
41. Gabriels L, Cosyns P, van Kuyck K, Nuttin B: DBS
for OCD. In: Lozano AM, Gildenberg PL, Tasker
RR, eds. Textbook of Stereotactic and Functional
Neurosurgery. Berlin, Heidelberg: Springer-Verlag; 2009:2897-2924.
42. Gallagher C: The return of lobotomy and psychosurgery. Cong Rec 118(26), 1972.
mography stereotaxic guidance

Neurosurg 59:217-222, 1983.
system.
54. Heller AC, Amar AP, Liu CY, Apuzzo ML: Surgery
of the mind and mood: a mosaic of issues in time
and evolution. Neurosurgery 59:720-733, 2006.
55. Henry TR, Votaw PB, Pennell CM, Epstein CM,
Bakay RAE, Faber TL, Grafton ST, Hoffman JM:
Acute blood ow changes and efcacy of vagus
nerve stimulation in partial epilepsy. Neurology
52:1166-1173, 1999.
56. Hodgkiss AD, Malizia AL, Bartlett JR, Bridges PK:
Outcome after the psychosurgical operation of stereotactic subcaudate tractotomy, 1979-1991. J Neuropsychiatry Clin Neurosci 7:230-234, 1995.
57. Hoffman JL: Clinical observations concerning
schizophrenic patients treated by prefrontal leucotomy. N Engl J Med 241:233-236, 1949.
43. George MS, Rush AJ, Marangell LB, Sackeim HA,

Brannan SK, Davis SM, Howland R, Kling MA,
Moreno F, Rittberg B, Dunner D, Schwartz T, Carpenter L, Burke M, Ninan P, Goodnick P: A oneyear comparison of vagus nerve stimulation with
treatment as usual for treatment-resistant depression. Biol Psychiatry 58:364-373, 2005.
58. Horsley V, Clarke RH: The structure and functions

of the cerebellum examined by a new method.
Brain 3:45-124, 1908.
44. Goktepe EO, Young LB, Bridges PK: A further review of the results of sterotactic subcaudate tractotomy. Br J Psychiatry 126:270-280, 1975.
60. Hosobuchi Y, Yingling C: The treatment of prolonged coma with neurostimulation. In: Devinsky
O, Beric A, Dogali M, eds. Electrical and Magnetic
Stimulation of the Brain and Spinal Cord. New
York: Raven Press; 1993:247-252.
45. Greenberg BD, Malone DA, Friehs GM: Three-year

outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 31:2384-2393, 2006.
46. Greenberg BD, Nuttin B, Rezai AR: Education and
neuromodulation for psychiatric disorders: a perspective for practitioners. Neurosurgery 59:717719, 2006.
47. Groves DA, Brown VJ: Vagal nerve stimulation: a
review of its applications and potential mechanisms that mediate its clinical effects. Neurosci
Biobehav Rev 29:493-500, 2005.
48. Halpern CH, Wolf JA, Bale TL: Deep brain stimulation in the treatment of obesity. J Neurosurg 109:
625-634, 2008.
49. Hamani C, McAndrews MP, Cohn M: Memory enhancement induced by hypothalamic/fornix deep
brain stimulation. Ann Neurol 63:119-223, 2008.
59. Hosobuchi Y, Adams JE, Rutkin B: Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol 29:158-161, 1973.
61. Hurley RA, Black DN, Stip E, Taber KH: Surgical

treatment of mental illness: impact of imaging. J
Neuropsychiatry Clin Neurosci 12:421-424, 2000.
62. Israel M, Steiger H, Kolivakis T, McGregor L,
Sadikot AF: Deep brain stimulation in the subgenual cingulate cortex for an intractable eating
disorder. Biol Psychiatry 67:e53-54, 2010.
63. Jankovic J: Tourettes syndrome. N Engl J Med 345:
1184-1192, 2001.
64. Joanette Y, Stemmer B, Assal G, Whitaker H: From
theory to practice: The unconventional contribution of Gottlieb Burckhardt to psychosurgery.
Brain Lang 45:572-587, 1993.
65. Jones DK, Simmons A, Williams SC: Noninvasive
assessment of axonal ber connectivity in the human brain via diffusion tensor MRI. Magn Reson
Med 42:37-41, 1999.
50. Han JH, Kushner SA, Yiu AP, Hsiang HL, Buch T,
Waisman A, Bontempi B, Neve RL, Frankland PW,
Josselyn SA: Selective erasure of a fear memory.
Science 323:1492-1496, 2009.
66. Kandel EI, Schavinsky YV: Stereotaxic apparatus

and operations in Russia in the 19th century. J Neurosurg 37:407-411, 1972.
51. Harlow JM: Recovery from the passage of an iron

bar through the head. N Engl J Med 39:389-392,
1848.
67. Kellaway P: The part played by electric sh in the

early history of bioelectricity and electrotherapy.
Bull Hist Med 20:112-137, 1946.
52. Hassler R, Riechert T, Mundinger F, Umbach W,

Ganglberger JA: Physiological observations in stereotaxic operations in extrapyramidal motor disturbances. Brain 83:337-350, 1960.
68. Kelly D, Richardson A, Mitchell-Heggs N, Greenup J, Chen C, Hafner RJ: Stereotactic limbic leucotomy: a preliminary report on forty patients. Br J
Psychiatry 123:141-148, 1973.
53. Heilbrun MP, Roberts TS, Apuzzo ML, Wells TH

Jr., Sabshin JK: Preliminary experience with
Brown-Roberts-Wells (BRW) computerized to-
69. Knight G: Stereotactic tractotomy in the surgical

treatment of mental illness. J Neurol Neurosurg
Psychiatry 28:304-310, 1965.
S24
70. Knight G: The orbital cortex as an objective in the

surgical treatment of mental illness. The results of
450 cases of open operation and the development
of the stereotactic approach. Br J Surg 51:114-124,
1964.
71. Kuhn J, Bauer R, Pohl S: Observations on unaided
smoking cessation after deep brain stimulation of
the nucleus accumbens. Eur Addict Res 15:196201, 2009.
72. Kuhn J, Lenartz D, Huff W: Remission of alcohol
dependency following deep brain stimulation of
the nucleus accumbens: valuable therapeutic implications? J Neurol Neurosurg Psychiatry 78:11521153, 2007.
73. Langevin JP, De Salles AA, Kosoyan HP, Krahl SE:
Deep brain stimulation of the amygdala alleviates
post-traumatic stress disorder symptoms in a rat
model. J Psychiatr Res 44:1241-1245, 2010.
74. Larsson B, Leksell L, Rexed B, Sourander P, Mair
W, Andersson B: The high-energy proton beam as
a neurosurgical tool. Nature 182:1222-1223, 1958.
75. Larsson B, Liden K, Sarby B: Irradiation of small
structures through the skull. Acta Radiol Oncol
Radiat Phys Biol 13:512-534, 1974.
76. Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie
G, Hamani C, Smith GS, Lozano AM: A phase I trial
of deep brain stimulation of memory circuits in
Alzheimers disease. Ann Neurol 68:521-534,
2010.
77. Lebensohn ZM: In memoriam, Walter Freeman.
1895-1972. Am J Psychiatry 129:356-357, 1972.
78. Leksell L: A stereotactic apparatus for intracerebral
surgery. Acta Chir Scand 99:229-233, 1949.
79. Leksell L: Stereotactic radiosurgery. J Neurol Neurosurg Psychiatry 46:797-803, 1983.
80. Leksell L: The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 102:316-19, 1951.
81. Leksell L, Larsson B, Andersson B, Rexed B,
Sourander P, Mair W: Lesions in the depth of the
brain produced by a beam of high-energy protons.
Acta Radiol 54:251-264, 1960.
82. Leksell L, Larsson B, Rexed B: The use of highenergy protons for cerebral surgery in man. Acta
Chir Scand 125:1-7, 1963.
83. Leksell L, Lindquist C, Adler JR, Leksell D, Jernberg B, Steiner L: A new xation device for the
Leksell stereotaxic system. Technical note. J Neurosurg 66:626-629, 1987.
84. Lewis ND: General clinical psychiatry, psychosomatic medicine, psychotherapy, group therapy,
and psychosurgery. Am J Psychiatry 105:512-517,
1949.
85. Lozano AM, Mayberg HS, Giacobbe P, Hamani C,
Craddock RC, Kennedy SH: Subcallosal cingulate
gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64:461-467, 2008.

86. Maciunas RJ, Maddux BN, Riley DE: Prospective

randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with
Tourette syndrome. J Neurosurg 107:1004-1014,
2007.
87. Mallet L, Polosan M, Jaafari N: Subthalamic nucleus stimulation in severe obsessive-compulsive
disorder. N Engl J Med 359:2121-2134, 2008.
88. Malone DA, Jr., Dougherty DD, Rezai AR: Deep
brain stimulation of the ventral capsule/ventral
striatum for treatment-resistant depression. Biol
Psychiatry 65:267-275, 2009.
89. Mantione M, van de Brink W, Schuurman PR, Denys D: Smoking cessation and weight loss after
chronic deep brain stimulation of the nucleus accumbens: therapeutic and research implications:
case report. Neurosurgery 66:E218, 2010.
90. Mayberg HS, Lozano AM, Voon V, McNeely HE,
Seminowicz D, Hamani C, Schwalb JM, Kennedy
SH: Deep brain stimulation for treatment-resistant
depression. Neuron 45:651-660, 2005.
100. Peneld W, Evans J: The frontal lobe in man: a

clinical study of maximal removals. Brain 58:115133, 1935.
101. Pressman JD: Sufcient promise: John F. Fulton
and the origins of psychosurgery. Bull Hist Med
62:1-22, 1988.
102. Puusepp L: Alcune considerazioni sugli interventi
chirurgici nelle malattie mentali [in Italian]. G
Acad Med Torino 100:3-16, 1937.
103. Quaade F, Vaernet K, Larsson S: Stereotaxic stimulation and electrocoagulation of the lateral hypothalamus in obese humans. Acta Neurochir (Wien)
30:111-117, 1974.
104. Rasmussen SA, Eisen JL: The epidemiology and
clinical features of obsessive compulsive disorder.
Psychiatr Clin North Am 15:743-758, 1992.
105. Rauch SL, Whalen PJ, Shin LM: Exaggerated
amygdala response to masked facial stimuli in
posttraumatic stress disorder: a functional MRI
study. Biol Psychiatry 47:769-776, 2000.
91. Melzack R, Wall PD: Pain mechanisms: a new theory. Science 150:971-979, 1965.
106. Raz M: Between the ego and the icepick: psychosurgery, psychoanalysis, and psychiatric discourse. Bull Hist Med 82:387-420, 2008.
92. Milad MR, Pitman RK, Ellis CB: Neurobiological

basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 66:10751082, 2009.
107. Rezai AR, Machado AG, Deogaonkar M, Azmi H,

Kubu C, Boulis NM: Surgery for movement disorders. Neurosurgery 62(Suppl 2):809-838, 2008.
93. Mindus P, Rasmussen SA, Lindquist C: Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding
frontal lobe function. J Neuropsychiatry Clin Neurosci 6:467-477, 1994.
94. Mitchell-Heggs N, Kelly D, Richardson A: Stereotactic limbic leucotomya follow-up at 16
months. Br J Psychiatry 128:226-240, 1976.
95. Moniz E: Essai dun traitement chirurgical de certaine psychoses [in French]. Bull Acad Med 115:
385-392, 1936.
96. Murray CJL, Lopez AD: The Global Burden of Disease: A Comprehensive Assessment of Mortality
and Disability From Diseases, Injuries, and Risk
Factors in 1990 and Projected to 2020. Cambridge:
Harvard University Press; 1996.
108. Richardson DE, Akil H: Pain reduction by electrical

brain stimulation in man. Part 1: acute administration in periaqueductal and periventricular sites. J
Neurosurg 47:178-183, 1977.
109. Rush AJ, Marangell LB, Sackeim HA, George MS,
Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka MM,
Nierenberg AA, Husain MM, Ginsberg D, Cooke
RG: Vagus nerve stimulation for treatment-resistant depression: a randomized controlled acute
phase trial. Biol Psychiatry 58:347-354, 2005.
110. Rush JR, George MS, Sackheim HA, Marangell LB,
Husain MM, Giller C, Nahad Z, Haines S, Simpson
RK, Goodman R: Vagus nerve stimulation (VNS)
for treatment-resistant depressions: a multicenter
study. Biol Psychiatry 47:276-286, 2000.
111. Salcman M: The cure of folly or The operation for
the stone by Hieronymus Bosch (C. 1450-1516).
Neurosurgery 59:935-937, 2006.
97. Nuttin BJ, Gabrils LA, Cosyns PR, Meyerson BA,

Andrewitch S, Sunaert SG, Maes AF, Dupont PJ,
Gybels JM, Gielen F, Demeulemeester HG: Longterm electrical capsular stimulation in patients
with obsessive-compulsive disorder. Neurosurgery 52:1263-1272, 2003.
112. Schiff ND: DBS Disorders of consciousness. In:

Lozano AM, Gildenberg PL, Tasker RR, eds. Textbook of Stereotactic and Functional Neurosurgery.
Berlin, Heidelberg: Springer-Verlag; 2009.
98. Oliver B, Gascon J, Aparicio A: Bilateral anterior

capsulotomy for refractory obsessive-compulsive
disorders. Stereotact Funct Neurosurg 81:90-95,
2003.
113. Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker

K, Gerber M, Fritz B, Eisenberg B, Biondi T,
OConnor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR: Behavioural improvements with thalamic stimulation after severe
traumatic brain injury. Nature 448:600-603, 2007.
99. Parrent AG: History of Surgery for Movement Disorders. In: Lozano AM, Gildenberg PL, Tasker RR,
eds. Textbook of Stereotactic and Functional Neurosurgery, Vol 2. Berlin. Heidelberg: Springer-Verlag; 2009:1467-1485.
114. Scoville WB: Selective cortical undercutting as a

means of modifying and studying frontal lobe function in man: preliminary report of forty-three operative cases. J Neurosurg 6:65-73, 1949.
115. Shahed J, Poysky J, Kenney C, Simpson R, Jankovic

J: GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities. Neurology 68:159-160, 2007.
116. Shin LM, Orr SP, Carson MA: Regional cerebral
blood ow in the amygdala and medial prefrontal
cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry 61:168-176, 2004.
117. Siegfried J, Shulman J: Deep brain stimulation. Pacing Clin Electrophysiol 10:271-272, 1987.
118. Simpson D: Phrenology and the neurosciences:
contributions of F.J. Gall and J.G. Spurzheim. ANZ
J Surg 75:475, 2005.
119. Sironi VA: Origin and evolution of deep brain stimulation. Front Integr Neurosci 5:42, 2011.
120. Spiegel EA, Wycis HT: Stereoencephalotomy. Proc
Soc Exp Biol Med 69:175-177, 1948.
121. Spiegel EA, Wycis HT, Marks M, Lee AJ: Stereotaxic
apparatus for operations on the human brain. Science 106:349-350, 1947.
122. Stone JL, Miles ML: Skull trepanation among the
early Indians of Canada and the United States. Neurosurgery 26:1015-1020, 1990.
123. Sun B, Li D, Zhan S: Surgical Treatment for Refractory Anorexia Nervosa. 8th World Congress of the
International Neuromodulation Society. 11th Annual Meeting of the North American Neuromodulation Society. Acapulco, Mexico, 2007.
124. Swayze VW: Frontal leukotomy and related psychosurgical procedures in the era before antipsychotics (19351954): a historical overview. Am J
Psychiatry 152:505-515, 1995.
125. Talairach J, Hecaen H, David M: Limited prefrontal
lobotomy by electrocoagulation of the thalamofrontal bers at the emergence of the anterior arm
of the internal capsule [in French]. Rev Neurol
(Paris) 83:59, 1949.
126. Tooth JC, Newton MP: Leucotomy in England and
Wales 19421954: Report on Public Health and
Medical Subjects No. 104. London: Her Majestys
Stationery Ofce; 1961.
127. Tsubokawa T, Yamamoto T, Katayama Y, Hirayama T, Maejima S, Moriya T: Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. Brain
Inj 4:315-327, 1990.
128. United States Department of Health, Education,
and Welfare: Determination of the Secretary regarding the recommendations on psychosurgery
of the National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research. Fed Regist 43:53242-53244, 1978.
129. Valenstein ES: Great and Desperate Cures. New
York: Basic Books; 1986.
130. Valenstein ES: History of Psychosurgery. In:
Greenblatt SH, ed. The History of Neurosurgery.
Park Ridge: AANS; 1997:499-516.
S25

131. Vassoler FM, Schmidt HD, Gerard ME: Deep brain

stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of
drug seeking in rats. J Neurosci 28:8735-8739,
2008.
132. Visser-Vandewalle V, Ackermans L, van der Linden
C: Deep brain stimulation in Gilles de la Tourettes
syndrome. Neurosurgery 58:E590, 2006.
135. Yamamoto T, Katayama Y: Deep brain stimulation

therapy for the vegetative state. Neuropsychol Rehabil 15:406-413, 2005.
136. Yehuda R: Post-traumatic stress disorder. N Engl J
Med 346:108-114, 2002.
133. Wernicke C: Der Aphasische Symptomen Complex

[in German]. Breslau: Max Cohn & Weigert; 1874.
137. Zitterl W, Demal U, Aigner M: Naturalistic course

of obsessive compulsive disorder and comorbid
depression. Longitudinal results of a prospective
follow-up study of 74 actively treated patients. Psychopathology 33:75-80, 2000.
134. Winer JL, Kim PE, Law M, Liu CY, Apuzzo ML: Visualizingthefuture:enhancingneuroimagingwithnanotechnology. World Neurosurg 75:626-637, 2011.
138. Zonenshayn M, Rezai A: Stereotactic surgery. In: Rengachary SS, Ellenbogen RG, eds. Principles of Neurosurgery. Edinburgh: Elsevier Mosby; 2005:785-819.
S26
Conflict of interest statement: The authors declare that the

article content was composed in the absence of any
commercial or financial relationships that could be
construed as a potential conflict of interest.
received March 15, 2012; accepted March 15, 2012
Archival Article Citation: World Neurosurg. (2012) 77, 5-6:662686.
http://dx.doi.org/10.1016/j.wneu.2013.08.002
Journal homepage: www.WORLDNEUROSURGERY.org
Available online: www.sciencedirect.com
1878-8750/$ - see front matter 2012 Elsevier Inc.
All rights reserved.
ID
3096140
Title
Surgery of the Mind, Mood, and Conscious State: An Idea in Evolution
http://fulltext.study/journal/2774
http://FullText.Study
Pages
25

Surgery of The Mind

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Surgery of The Mind

Uploaded by

Copyright:

Available Formats

Peer-Review Reports

Since the beginning of recorded history, humans have sought

deep-brain stimulation now aims to reversibly alter and

Department of Neurological Surgery, Keck School of Medicine, University of

WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2013.08.002

PEER-REVIEW REPORTS: FRONTIERS