Nijensohn 0914v2.indd - Dr. Daniel E. Nijensohn

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Daniel e. nijensohn, MD, Msc, PhD anD isaac GooDrich, MD. ABSTRACT ..... Department of Neurosurgery, Yale, 1977 (clockwise from top row, left): henry Yu, coauthor Daniel nijensohn, joseph Piepmeier, richard. Bucholz ... 7. anderson De.
Psychosurgery: Past, Present, and Future, Including Prefrontal Lobotomy and Connecticut’s Contribution Daniel E. Nijensohn, MD, MSc, PhD and Isaac Goodrich, MD

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ABSTR ACT — Psychosurgery, a subspecialty sychosurgery is a subspecialty of functional of functional neurosurgery, has been used in the neurosurgery. Prefrontal lobotomy (leucotomy, treatment of psychiatric illness, intractable pain, leukotomy), as the operation was popularly known, and, controversially, as a means to control and modify was a psychosurgical procedure used in the mid-20th century. violent human behavior. Major advances have Prefrontal lobotomy, a ensued since the early days procedure developed in of prefrontal lobotomy in the 20 th century, arose as a result of pioneering the 1930s and 1940s. Iniresearch, including work tially, this happened when done at Yale University in minimalism, stereotaxis, New Haven. Prominent greater surgical precision, clinicians throughout and better understanding Connecticut contributed of the neuroanatomical to the development of targets improved the ablamodern psychosurgery. tive techniques. Further advances up to the present Neuroethics or ethics of include: deep brain stimuneuroscience is essential lation, neuromodulation, to the study and practice use of open-loop and of psychosurgery. closed-loop neurostimuNew technology has pro- Figure 1. Early prehistoric attempt at trepanation (a hole in the skull lation, surgical navigation, vided improved accuracy produced surgically) from Peru.3 nanomedicine, robotics, with less morbidity. The neuropharmacology and neurochemistry, genetic moprogressive replacement of ablative procedures with lecular manipulation, the use of embryonic stem cells deep-brain stimulation and restorative neurosurgery for restoration, in vivo determination of intracerebral offers new perspectives in the treatment of some chemical neurotransmitter level changes, functional psychiatric conditions. magnetic resonance imaging, and electromagnetic Daniel E. Nijensohn, MD, MSc, PhD, Honorary encephalography. Professor, Department of Neurosurgery, Yale University School The field of neuroethics or ethics of the neurosciences of Medicine, New Haven, Emeritus Chief of Neurosurgery, St. Vincent’s Medical Center, Bridgeport, Honorary Staff, Bridgeport has played a prominent, at times controversial, role in the Hospital, Bridgeport, Former Staff, Yale New Haven Hospital and progress of psychosurgery. Yale Gamma Knife Center, New Haven; Isaac Goodrich, Early prehistoric attempts at trepanation,1-5 (Figure MD, Honorary Professor, Department of Neurosurgery, Yale University School of Medicine, New Haven, Past Chief of 1) Aristotle, Descartes, Gall, Broca and Wernicke, the Neurosurgery, Hospital of St. Raphael, Past Associate Chief of Phineas Gage case, Harlow, Ferrier, Burckhardt, and Neurosurgery, Honorary Staff, Yale New Haven Hospital, New Haven; Corresponding author: Daniel E. Nijensohn, MD, others, preceded great advances in the fields of neuroMSc, PhD, [email protected]. anatomy, neurophysiology, and neuropsychology, imvolume 78, no. 8

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Figure 2. Prefrontal lobotomy (leucotomy, leukotomy) as per Egas Moniz.

portant factors in the development of psychosurgery.6-25 At the start of the 20th century, the few early attempts at psychosurgery were, in general, met with disregard and strong criticism. The Development of Prefrontal Lobotomy John Fulton at Yale University was the true pioneer of prefrontal lobotomy 26 (Figure 2). This psychosurgical procedure involves surgical interruption of nerve tracts to and from the frontal lobe of the brain. It was first performed in Portugal in 1935, when a medical team composed of a neurologist, Egas Moniz (1874-1955), and a neurosurgeon, Pedro Almeida Lima (1903-1985), began operating on patients with psychiatric illness.27-28 Moniz thought the prefrontal region of the brain was the psychic center of the person. He strongly believed that a person with mental illness would not change on his own but could be cured by severing the connections responsible for such behavior. Egas Moniz’s work on prefrontal lobotomy earned him the Nobel Prize in Physiology or Medicine in 1949, for his contribution of “immense importance for the problems of psychiatric treatments.”29-30 Being a medical neurologist, and suffering from severe gouty arthritis that deformed his hands, he invited his colleague Dr. Lima to perform the surgical procedure. Although their

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first patient suffered from significant apathy and blunted affect after the procedure, they felt the operation was an overall success, having “rid her of her psychosis.” In 1939, a patient who suffered from schizophrenia shot Moniz. He partially recovered from his injuries, and subsequently retired in 1944. Moniz’s operation was initially heralded as the birth of “a new psychiatry,” and was considered akin to the ability to “pluck from the brain a hidden sorrow.”31 The Second International Neurological Congress was held in the summer of 1935 in London, England. The main subject of the congress was the function of the frontal lobes. This was a landmark plenary session for psychosurgery. Carlyle F. Jacobsen and John Farquhar Fulton from Yale University presented their research findings,32-34 which inspired Egas Moniz who along with Lima also attended the meeting. Jacobsen was a graduate student in psychology at Yale University, working at Fulton’s (1899-1960) physiology department in New Haven, then considered to be the best in the world. He was pursuing experimental research on chimpanzees at the Yale Primate Laboratory. Two female chimps, Becky and Lucy, had shown decreased stress and “lack of neurotic behavior” after frontal lobotomy. “Frontal and prefrontal cortical damage in chimpanzees led to a massive reduction in aggression, connecticut medicine, september 2014

while complete removal of the frontal cortex led to the inability to induce experimental neuroses.” The chimps were noted to be “devoid of emotional expression” and had loss of the “frustrational behavior” previously noted when they failed to receive an anticipated reward.34 Many consider Fulton should have at least shared the 1949 Nobel Prize with Moniz. 35 Distinguished neuroscientists passed through his lab, including Paul Bucy, James Watts, José Delgado, 36 and others. Fulton obtained funds from the Research Council for the Yale Connecticut Cooperative Lobotomy Study through the Veterans Administration. 37 His influence was a powerful force for the development of psychosurgery in Connecticut. As a result of work done in his laboratory, Hartford, New Haven, and Bridgeport neurosurgeons working at the Connecticut State Hospital, Norwich State Hospital, and at the Institute of Living in Hartford started performing prefrontal lobotomies in the 1940s. Fulton was instrumental in giving credibility to the operation. Initial Surgical Techniques and Approaches in Prefrontal Lobotomy and Other Psychosurgical Interventions Dr. James L. Poppen was the chief of neurosurgery at the Lahey Clinic in Boston, MA. Evidence that he performed a prefrontal lobotomy on Eva Perón in Buenos Aires in 1952 was discovered by Nijensohn et al.38-39 She had exhibited uninhibited violent and aggressive behavior and experienced severe pain from metastatic cervical cancer. This was a research project led by the senior author and an impetus to write this paper. Poppen started a program of open prefrontal lobotomy as early as 1943, working on patients at the Boston Psychopathic Hospital.40 The role New England — particularly Connecticut — played in the development of prefrontal lobotomy was significant. In Connecticut, John Fulton, Carlyle Jacobsen, William Scoville, José Delgado, and others, contributed to the development of modern psychosurgery. Prominent psychosurgeons, including Walter Freeman, James Watts, Michael Apuzzo, and Kendall

Lee, spent time at Yale University. Several state neurosurgeons performed psychosurgery. Multiple surgical approaches were subsequently employed by many surgeons.41-57 In Connecticut, William B. Scoville58 performed selective undercutting of the prefrontal cortex. He accumulated a large surgical experience. Irving J. Sherman in Bridgeport (personal communication) and others throughout Connecticut amassed their own personal surgical series. Thomas Ballantine59 remained for a few years as one of the very few neurosurgeons still doing psychosurgery and stereotactic cingulotomy after the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974-1978) produced the Belmont Report.60 The report did not ban psychosurgery but made restrictive recommendations. Except for Ballantine and a few others, neurosurgeons lost interest with psychosurgery and its associated political, social, and legal implications. Dr. Walter Freeman and Dr. James Watts (Figure 3) started their involvement in psychosurgery in 1936.61-63 In 1942, Freeman and Watts published the first edition of their classic monograph, “Psychosurgery.”61 Freeman was a neurologist who did his undergraduate studies at Yale University. He became active and enthusiastic in psychosurgery. He worked with neurosurgeon, Dr. James Watts. On September 14, 1936, they performed the first frontal lobotomy in the United States. The patient suffered from depression, anxiety, and insomnia. Although the patient developed some postoperative language problems, she was noted to remain calm and devoid of her previous anxiety. This relative success encouraged Freeman and Watts. In 1942 they reported a series of two hundred cases, with 63% of patients reported as improved and 23% unchanged. Fourteen percent had a negative outcome that included what they described as a “frontal lobe syndrome,” seizures, and uncontrollable bleeding (often resulting in death).61-63 Following Dr. Amarro Fiamberti’s 1937 report published in Italy on a transorbital approach to the frontal lobe, Freeman started using this approach

Figure 3. Dr. Walter Freeman and Dr. James Watts.

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together with Watts. Using an icepick tool on a patient anesthetized by electroshock, they performed their first transorbital lobotomy in 1945.63 The procedure would take approximately fifteen minutes in Freeman’s hands. He soon dropped all sterility caution, refusing cap, mask, and gloves, and set off on an evangelistic-like cross-country tour to popularize his technique. This and more resulted in a split with Dr. Watts.6 He taught the technique to psychiatrists, and expected them to do the operation on their patients, creating a wide negative reaction from the medical and, particularly, from the neurosurgical community. Freeman became associated with the Department of Veterans Administration (VA) and obtained a contract to perform lobotomies on veterans suffering from a myriad of psychological symptoms. Today, many of them would be classified as suffering from posttraumatic stress disorder (PTSD). The diagnosis at that time included schizophrenia, paranoia, depression, and personality disorders. There was early resistance from distinguished neurosurgeons that acted as consultants for the VA, among them Murphey and Spurling.64 In 1967 Freeman performed his last leucotomy. A cerebral vessel was torn during the surgical procedure resulting in the patient’s death, subsequent removal of Freeman’s surgical privileges, and his retirement from psychosurgical practice. Rise and Decline of Prefrontal Lobotomy as Treatment of Psychiatric Illness and Other Conditions Psychosurgery became widely accepted in the United States and in the rest of the world. There were no effective alternatives such as psychoactive medications until chlorpromazine (Thorazine) was developed in 1953. Between 1949 and 1952 some five thousand lobotomies a year were performed in the United States alone, a third of them through a transorbital approach. Overall, some forty thousand were done worldwide.6 There was overcrowding in psychiatric institutions. At that time psychiatric patients occupied over half of all hospital beds in the United States. A 1937 report on the state of mental illness in the United States estimated that there were about half a million patients institutionalized in almost five hundred asylums, with nearly one half of them remaining in the hospital for five years or longer. Increasing cost of caring for the mentally ill became a growing concern. A “miracle cure” for mental illness was sought. The absence of adequate treatment led to deplorable conditions in mental institutions. Frontal lobotomies seemed to offer hope for an effective treatment of some mental illness.

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Successful cases of lobotomies were praised in numerous publications, including Life, Time, The New York Times, Reader’s Digest, and Harper’s. There was a time, in the late 1940s and early 1950s, when there still were no clear bioethical controls. At the time lobotomies represented technological innovation and the state of the art. They were seen as procedures to manage mental disease. Psychosurgery was seen at first as a drastic act justified by desperate circumstances, the latest technological solution to a range of problems that had no good treatment at that time.2,65-66 Initially it was a procedure of last resort. Later, it was done for less precise indications, and neurosurgeons, even at the peak of popularity of the procedure, realized it was imprecise and potentially dangerous. Morbidity and mortality from the procedure started to rise. The indiscriminate use of psychosurgical procedures led to increased complications.67-68 Psychosurgery evolved into not being used solely as a last resort. Cases were reported in which little clinical investigation had been undertaken before the operations were performed. Then, psychoactive drugs were introduced into therapeutic use, including chlorpromazine and subsequently lithium, reserpine, haloperidol, antidepressants, and antipsychotics. In the 1960s, increasing debates and controversy, as well as availability of drug therapy led to society’s rejection of the procedures. Psychosurgery was seen by some as an attempt at social control cloaked in the ideology of science. Many of the patients were female and belonged to minorities. Bioethicists raised their voices.20 According to Robison et al, “The subsequent social and ethical ramifications of the widespread overuse of transorbital lobotomies drove psychosurgery to near extinction.”58 Derogatory books and movies followed. Ken Kesey’s “One Flew Over the Cuckoo’s Nest” in 1962,i “The Planet of the Apes” (1968), “A Clockwork Orange” (1971), “Frances” (1982), and others fueled a popular outcry. In Tennessee Williams’ play “Suddenly Last Summer” (1958) an elderly woman attempts to persuade a neurosurgeon to perform a lobotomy on her niece to prevent her from revealing a secret. Michael Crichton’s 1972 novel and movie “The Terminal Man” 69-70 was based on the work of José Delgado at Yale University. It showed a relationship between violence induced by brain seizures and attempts to control the mind remotely through i Kenneth Elton Kesey (1935-2001) himself participated in the MK-ULTRA project; an illegal human experimentation program ran by the Central Intelligent Agency (CIA). This program included the use of LSD and other psychedelic drugs.

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computers and implanted brain electrodes.ii “Violence and the Brain” by Vernon Mark and Frank Ervin in 1970 postulated that psychosurgery might eventually be used by governments for widespread mind control. Public fascination in the history of lobotomies is exemplified by Jack El-Hai’s “The Lobotomist” (2005), which was broadcasted as a PBS documentary. Prefrontal Lobotomy as Treatment of Intractable Pain Prefrontal lobotomy was also performed in selected patients with intractable pain, whether of organic or functional nature, when less invasive measures failed. This began being utilized in the mid-1940s, particularly on patients with cancer-related pain.71 Pain management was primitive and ineffective. Opiates were given in small doses with concern for addiction. Up to 60% of patients exhibited a good response after lobotomy. Pain relief itself might not be achieved but having a lack of emotional response was apparent. The patients would no longer seem to care even if they continued to suffer from pain. In 1946 Freeman and Watts reported improvement on patients suffering from intractable pain in cancer cases after bilateral prefrontal lobotomy.72 Prefrontal Lobotomy for Control of Aggression, Violence, and Belligerence, Psychosurgery for Mind Control Prefrontal lobotomy was performed for control of aggression and for behavior modification. The surgery was done on patients with “undesirable habits” to “make them quiet, placid, and uncomplaining.” A new “malleability” would develop and as a result of it, the operation would be indicated for hospitalized patients who were “difficult to manage.” In 1948, Dr. Mixter at Harvard asserted “we usually do a lobotomy to quiet people down.” 46,73 Lobotomies were performed because of obnoxious behavior or simply to correct “maladjustment.” It was also done routinely in the American state prison system, such as Vacaville and Atascadero in California, now incompatible with current medical ethics.74 However, for a period of time, multiple physicians advocated psychosurgery for behavior modification. After the 1965 Watts riots in Los Angeles and those of 1967 in Newark and Detroit, Vernon Mark, a ii

José Manuel Rodriguez Delgado, a Spaniard working at Yale in the 1950s and 1960s, did what are now considered classical experiments on physical control of the mind, using bulls. Remotely, through electrodes placed in the bull’s brain, he could make the bull drop and stop its charge in the midst of a bullfight. This experiment was also done on monkeys.36

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neurosurgeon, Frank Ervin, a psychiatrist, and William Sweet, a professor of neurosurgery at Harvard, advocated psychosurgery for violent behavior.75 They remarked that the riots could not have been caused by political conditions alone. They concluded that violent protesters may have had brain disease, and they recommended large-scale screening and treatment. They spoke about what they described as “unacceptable violence” in both the personal and political arena, appealed to “law and order” and implied that up to 10% of Americans had brain disease that might require treatment. William Scoville of Yale and Hartford also advocated the use of psychosurgery for psychopaths. Some psychosurgeons proposed their approach for wide-scale social control. Delgado (Yale) advocated “physical control of the mind,” including psychosurgery, for the control of domestic and international violence in the political sphere. In 1971, Freeman championed psychosurgery noting its usefulness within large institutions. It seemed to be the “ideal operation for use in crowded state mental hospitals with a shortage of everything except patients.”36 The procedure became the operation of choice for treatment of “intractable and uncontrollable aggression, independent of any brain disease.” As such, it was advised to treat people with rage, fear, and depression, what Sano would call “sedative surgery.” This evolved into more precise and targeted procedures, such as cingulotomy, thalamotomy, amygdalotomy, and hypothalamotomy. Many discussed the ethical and political implications of these pacifying operations. Psychosurgery was eventually seen as a particular menace to vulnerable individuals, precisely mental patients, captive children in state institutions, or incarcerated adults in state prisons. They were under the control of authorities whose major intention was to manage them in the most economical and most efficient manner. The 1972 Third International Congress of Psychosurgery held in Tokyo, was disrupted by large popular street demonstrations. Psychosurgery, however, persisted.76 The use of psychosurgery for political means was seen as a potential menace. Mark and Ervin advocated a national screening program for the identification and treatment of potentially violent people.77 José Delgado proposed a NASA-styled program to infuse a large amount of money into physical control of the mind.36 The psychiatrist Robert Heath (1915-1999) performed controversial experiments by doing electric stimulation of the septal region for the initiation of heterosexual activity in a homosexual male, as a “cure” for homosexuality. Psychosurgery was used on political prisoners and dissidents in totalitarian societies and regimes. The Soviet Union used psychiatry as a tool of the state to limit political opposition, hospitalizing dissidents in asylums and other psychiatric hospitals. In contemporary times 457

Russia and China have been involved in controversy over the use of psychosurgery as treatment of heroin and other drug addictions.6,66,77

situations where the IRB believes there is no informed consent to such procedure.” Exceptions contemplated by the commission are when a specific psychosurgical procedure “is determined by the psychosurgery advisory board to have a demonstrable benefit for the treatment of an individual with a specific psychiatric symptom or disorder.”82 Various reviews mandated by Congress concluded that psychosurgery should continue. Initially a ban was considered on psychosurgery, but the investigation by Congress provided evidence of the efficacy of the more modern and more localized lesioning procedures, calling for further research into similar treatments. Congress recommended more caution and control, while acknowledging the need for surgical intervention of the brain as treatment of intractable psychiatric illness, and chronic or intractable pain. 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.

Neuroethics In 2008, Joshua J. Wind and Douglas E. Anderson78 published an article describing and analyzing the history of psychosurgery with an introduction to the field of “neuroethics.” Adina Roskies refers to informed consent and guidelines as the “ethics of neuroscience.” The subject of understanding the neuroscientific bases of moral thought, as a distinct human activity of reasoning and emotion is what Roskies terms the “neuroscience of ethics.”79 Current bioethical principles ruling medical care are the norm in democratic western societies. Careful monitoring and informed consent are part of modern medicine. Psychosurgery, together with revelations arising from the Tuskegee Syphilis Study, prompted Congress in 1974 to pass the National Research Act, which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Increased Precision and Minimalism commission discussed the lack of competency of institutionalized patients to give consent to psychosurgery The historic development of the minimalist era of and described a set of guidelines for research and experi- psychosurgery is thoroughly described by Apuzzo and his mentation. Psychosurgery was deemed inappropriate for colleagues (Robison et al) in a recent article.58 Apuzzo, a leader of modern neurosurgery, is originally from New children by the Commission.80 The Declaration of Helsinki is a set of ethical principles Haven and did his neurosurgical residency at Yale. regarding human experimentation, developed for the medical community by the World Medical Association.81 Behavior altering surgery done without clear informed consent and considering the interest of society and not that of the individual is contrary to present ethical standards. Guidelines for psychosurgical interventions were developed by the U.S. commission headed by Kenneth John Ryan (1926-2002). Among the recommendations were that psychosurgical procedures should be performed only at an institution with an institutional review board (IRB), and only on adult patients. The commission also stated: “a psychosurgery procedure should not be performed on an adult patient who: 1) is a prisoner, 2) is involuntarily committed to a Figure 4. Diagram of deep-brain stimulation (DBS). mental institution and, 3) in other 458

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Ablative procedures using advances in stereotaxis, imaging, neurophysiology, neurochemistry, computers and robotics, include anterior capsulotomy (Talairach);83 subcaudeate tractotomy (Knight);55 anterior cingulotomy (Ballantine);59 and limbic leukotomy (Cosgrove).84-86 Improvements over the past decades have made the surgical procedures more selective and accurate, safer and with far fewer side effects, and less postoperative morbidity and mortality. Incremental technical and neuroscientific innovations have allowed for safer treatments. These, accompanied by recent decades of surgical minimalism, noninvasive imaging, and functional manipulation of the human brain, created new procedures for the treatment of disorders of the human mind and mood. The ability to create minute and accurately placed lesions in the brain has allowed for a variety of surgical therapies to be developed. Deep-Brain Stimulation More recently, ablative procedures have been progressively replaced by techniques of stereotactic deep-brain stimulation and neuromodulation of neurological circuitry, as treatment of intractable psychiatric illness,87-88 chronic and/or intractable pain, and other neurological conditions. Brain stimulation has evolved since the days of Wilder Penfield from superficial electrical brain stimulation (EBS) to deep-brain stimulation (DBS) of Delgado and many others.88-90 While EBS fails to elicit emotional reactions in humans, DBS (Figure 4) elicits both pleasurable and aversive responses in man. DBS in various structures of the brain may evoke or calm pain, rage, fear and anxiety, premonitions of disaster, depression, and aggression. Stimulation of the amygdala produces electricallyinduced aggression both in animals and in humans. DBS of the septal regions results in pleasurable sensations, even euphoria 91-92 (Figure 4). In the 1950s and ‘60s José Delgado at Yale invented the “stimoceiver,” a radio transmitter and receiver, which was used to remotely stimulate the brain via implanted electrodes, recording via another channel electroencephalography (EEG) brain waves. He also invented the “chemitrode,” an implantable device that could be used to inject and slowly release chemical substances into test subjects. This was the precursor of Kendall Lee’s current device at the Mayo Clinic. Deep-brain stimulation, neuromodulation, using the Wireless Instantaneous Neurotransmitter Concentration Sensory System (WINCS) is advocated by Kendall H. Lee, a former Yale student, presently a neurosurgeon at the Mayo Clinic Neural Bio-Engineering Laboratory. volume 78, no. 8

This apparatus is utilized to disrupt disordered neurocircuitry, treating refractory psychiatric illness with neuromodulation. The WINCS detects and measures levels of neurotransmitters such as serotonin (thought to have a key role in controlling depression) released in the brain.93-95 Lee’s group found that a functional MRI signal correlates with in vivo neurochemical release evoked by deepbrain stimulation in the porcine animal model.93The group used functional magnetic resonance imaging and in vivo neurochemical monitoring. The wireless monitoring device supports an array of electrochemical measurements that includes fast-scan cyclic voltammetry for real-time in vivo monitoring of the release of dopamine, serotonin, and other neurotransmitters utilizing carbon-fiber microelectrodes. His group has noted that fornix deep-brain stimulation induces functional activation in hippocampal circuitry. This holds promise as an approach to address memory deterioration associated with Alzheimer’s and other dementias.94-95 Recently, UCLA announced receiving a grant from the Defense Advanced Research Projects Agency (DARPA) to develop a wireless, implantable brain device or prosthesis to help restore lost memory function after brain injury and other disorders. The lead investigator is Dr. Itzhak Fried, a graduate of the Yale neurosurgical residency program and a professor at UCLA. It is based on his work on stimulation of the brain’s entorhinal cortex, considered the entrance to the hippocampus or the “golden gate” to the brain’s memory mainframe. Fried developed some of his ideas while working under Dennis Spencer in New Haven.96 The Mayo Clinic group proposes the nucleus accumbens as a potential target for central poststroke pain.97 In August 2013, Torres et al98 published in the Journal of Neurosurgery the long-term results of posteromedial hypothalamic deep-brain stimulation for patients with resistant aggressiveness. The clinical work was done on patients suffering from erethism, characterized by unprovoked aggressive behavior. Those patients also suffered from some degree of mental impairment and gross brain damage. The hypothalamus appears to contain a crucial group of nuclei that coordinate behavioral and autonomic responses and play a central role in the control of aggressive behavior. Deep-brain stimulation of the posteromedial hypothalamus has been proposed as a treatment for resistant erethism. In addition to deep-brain stimulation, vagal nerve stimulation (VNS), initially used to treat epilepsy, has also been tried successfully to treat depression, anxiety, obesity, cognition and memory deficits, and other psychiatric illnesses.99-100

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Figure 5. Department of Neurosurgery, Yale, 1977 (clockwise from top row, left): henry Yu, coauthor Daniel nijensohn, joseph Piepmeier, richard Bucholz, coauthor isaac Goodrich, Dennis spencer, William collins, joan Venes, Barry chehrazi, and an unidentified physician assistant. Inset photo (from left to right): Yale neurosurgery clinical Faculty and Guest speaker, new haven, 2001: Franklin robinson, Michael apuzzo (world known psycho-neurosurgeon and graduate of the Yale neurosurgical training residency program, guest), isaac Goodrich, lycurgus Davey, and Daniel nijensohn.

The Future Modalities in the future may include targeted drug delivery using specific nanomolecules or invasive local delivery methods such as 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 increasing microscopic — even molecular or nanoscale interventions — to target the pathologic neuronal function responsible for the spectrum of intractable psychiatric illness.101-103 The development of neuroscience continues at a breathtaking pace. on september 13, 2012, robert e. hampson et al reported (in the Journal of Neural Engineering) a brain implant that sharpened decisionmaking and restored lost mental capacity in monkeys. This represents the first demonstration in primates of the type of “brain prosthesis” that could eventually aid patients with damage from dementia, strokes, or other brain abnormalities.104-106 460

lozano101 emphasized the fact that there has been a general trend over the last few decades towards less invasiveness, coupled with better understanding of dysfunction, better imaging capabilities and neurosurgical techniques. Functional neurosurgery offers hope for treatment in epilepsy, depression, Parkinson’s, and alzheimer’s. concerning depression, comparisons of brain activity in patients with and without melancholia, have led to the discovery of areas of the brain that are hyperactive, such as area 25, which is associated with feelings of sadness. at the same time, the frontal lobes are hypoactive. a Phase iii trial for depressed patients is now under way with neuromodulation using deep-brain stimulation in area 25. also, trials on rats have shown that deep-brain stimulation of the fornix, the main inflow and outflow path of the hippocampus, increases neuronal growth, making the rats “smarter.” Deep-brain stimulation of the hippocampus in patients with alzheimer’s may improve their memory.107 researchers at columbia found the first evidence that selective activation in mice of the dentate gyrus, a portion of the hippocampus, can reduce anxiety without affecting learning.108 connecTicUT MeDicine, sePTeMBer 2014

In an alternative form of stimulation of the brain, it is possible to use light. An experiment was devised by Karl Deisseroth109 of Stanford University, developer of “optogenetics,” using gene therapy to introduce channels of neurons that are light-sensitive. The channels contain light sensitive algae protein. Shining a light on them causes them to open or close making it possible to turn individual neurons on and off just by using light beams. It might be possible to turn on the mood circuit so, in the future, we may not only use electricity but also light to activate and modulate the activity of those circuits. Conclusion Prefrontal lobotomy as one of many procedures within the field of psychosurgery was the culmination of a long history of developments that started in prehistoric times. Clinical psychiatrists and neurologists, neurosurgeons, psychologists, physiologists, neuroscientists, and researchers in New England, particularly in Connecticut (primarily New Haven, Hartford, and Bridgeport), and mostly associated with Yale University (Figure 5), contributed to the development of modern psychosurgery in the 20th century. Psychosurgery has been used as a treatment of psychiatric illness, intractable pain,110-111 and as a means to control and modify violent human behavior. The latter has been the source of multiple books, speeches, and motion pictures. The threat of psychosurgical procedures to society for reasons other than purely medical ones has occurred in the past both in totalitarian regimes as well as in some democratic states. A major threat is when it is used for political purposes. Ethics of neuroscience is essential in the present psychosurgical guidelines and in the study and practice of psychosurgery.112 Psychosurgery continues to be selectively used, in its more contemporary and refined technologically advanced forms. REFERENCES 1. Alt KW, Jeunese C, Buitrago-Tellez CH, et al. Evidence for Stone Age cranial surgery. Nature. 1997;387(6631):360. Erratum in Nature 1997;387(6635):768. 2. Piedimonte FC, Piedimonte L. Historia de la Psicocirugía. NeuroTarget. 2009;4(1):8-25. 3. Kurin D S. Trepanation in South-Central Peru during the early late intermediate period (ca. AD-100-1250). Am J Phys Anthropol. 2013;152(4):484-494. 4. Díaz-Farfan R. Los primeros neurocirujanos de América: pre y postoperatorio en las trepanaciones Incas. Rev Argent Neuroc. 2008; 22 (4): 197-201. 5. Flamm ES. From Skulls to Brains. New York, NY: AANS, The New York Academy of Medicine; 2008. 6. Valenstein ES. Great and Desperate Cures: The Rise and Decline of Psychosurgery and Other Radical Treatments for Mental Illness. New York: Basic Books; 1986.

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