, John Williams1, Jacob Chodakiewitz2 and Garth Rees Cosgrove1
(1)
Department of Neurosurgery, Alpert Medical School, Brown University, Providence, USA
(2)
Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, USA
5.1 Historical Perspective
The history of surgical intervention for psychiatric disorders is a long, complex, and controversial one. The original use of surgical methods to treat symptoms of the mind occurred in the prescientific era as far back as antiquity. The ancient practice of trephination involved using a cylindrical saw to perform craniotomy. Literature dating back to 1500 BC can be found describing trephination to relieve psychiatric symptoms, including affective and psychotic disorders [1]. It can further be surmised that surgical trephination was occurring as far back as 5100 BC, based on carbon dating of a trephined skull, which showed evidence of proper healing to suggest a surgical wound origin rather than a traumatic origin, found at the Enshisheim burial site in France [2].
The modern scientific era of psychosurgery can find its origins in the 19th century, when strong correlates between brain and behavior were starting to be drawn. Much of this work was done through clinicopathologic correlates of particular neurological insults leading to particular cognitive dysfunction, as seen in the language aphasias described by Broca and Wernicke from patient autopsy studies [3, 4]. The case in 1848 of Phineas Gage, a railroad worker who suffered an accident involving a sharp rod piercing his skull and his brain’s frontal lobe, is another famous example [5]. In Gage’s case, physically, he recovered surprisingly well. However, he was noted by those who knew him to have an undergone an obvious and significant personality change.
It was in this environment of brain-behavior correlative science in the mid-late 1800s that present day psychosurgery came into being, with the Swiss psychiatrist Gottlieb Burckhardt performing the first procedures in 1888. Working to clinically apply the developing theories of neuropsychiatric correlations, he performed bilateral topectomy, which involved selective excision of cortex from multiple foci [1, 6]. These early attempts were not clearly successful, and psychosurgery (a term not yet coined was not particularly accepted by the neuropsychiatric community. Years later in the 1930s, Fulton and Jacobson demonstrated calming behavioral changes, along with some changes in overall cognition, in chimpanzees as a result of surgical bilateral frontal lobe lesions [7, 8]. This work by Fulton and Jacobson particularly influenced the Portuguese neurologist Egas Moniz, who subsequently began proposing the idea that an efficacious psychosurgical procedure to relieve anxiety states in people would involve interruption of afferent and efferent fibers of the frontal lobe [9, 10]. Furthermore, it was in fact Moniz who coined the term “psychosurgery” [10, 11]. Together with his neurosurgical colleague Almeida Lima, Moniz and Lima developed the procedure that came to be known as the prefrontal leukotomy or lobotomy for psychiatric disease [12].
Moniz’ and Lima’s original procedure involved the injection of alcohol into frontal lobe white matter to sever connections apparently giving rise to mental illness [13]. Their first patient was a 63 year old woman suffering from paranoid delusions, anxiety and melancholia; the operation was deemed an overall success in terms of ridding the patient of her psychosis and anxiety, though she remained with significant apathy and a blunted affect after the procedure [8, 13]. Moniz and Lima continued to refine their prefrontal leukotomy procedure, devising an instrument known as the leukotome to make their lesions rather than their original use of alcohol injections, which otherwise often required several procedures for repeat injections. The leukotome consisted of a rod with a retractable wire loop that could be inserted into the white matter and rotated to create series of small circular lesions within the frontal lobe white matter tracts [8, 10, 13]. This procedure for psychiatric disease was now becoming much more accepted by the community and resulted in Moniz receiving the Nobel Prize in Medicine/Physiology for this work in 1949 [14].
Starting already in 1936, the neurologist Walter Freeman and the neurosurgeon James Watts began adapting Moniz’ and Lima’s prefrontal leukotomy in the US. The Freeman-Watts prefrontal lobotomy was performed via bilateral posterior frontal burr holes through which a smooth, blunt, calibrated blade was inserted to the midline and then swept up and down to disconnect the frontal lobes at the level of the genu of the corpus callosum [15].
At the time in the US, there were still no effective psychoactive drugs available and psychiatric disease posed a particularly significant public health problem. In the late 1930s and early 1940s, there were 477 American psychiatric institutions housing over 400,000 patients and treatment of psychiatric illness was costing $1.5 billion annually [16, 17]. It had been argued that more widespread use of prefrontal leukotomies would save American taxpayer $1 million per day, by relieving the heavy costs of funding the asylums [18]. Within this context of the great burden posed to society by mental illness, Freeman further evolved the procedure and fervently promoted it in a mass-market fashion.
By 1948, Freeman began promoting his own modified surgical technique using a transorbital approach [19]. Before this modification, the prefrontal leukotomies had to be carried out by experienced neurosurgeons under operating room conditions to gain appropriate intracranial access; these were conditions not widely available in the psychiatric institutions. Freeman intended his transorbital leukotomy to be simple and quick enough so that the procedure could be performed in the office-setting by non-surgeons. The modified procedure involved using an icepick-like instrument, known as an orbitoclast, inserted underneath the upper eye-lid but over the eye globe and then driven by a mallet through the orbital roof to a desired distance of 7 cm into the frontal lobe white matter. At that point, the orbitoclast would be swept side to side with a deft wrist movement to complete the lesion before being removed. The need for an anesthetist was also eliminated, as the procedure was performed on the patient in the immediate post-ictal phase after an electroconvulsive treatment [8, 10, 13, 19]. Freeman fervently popularized this procedure, opening up an infamous chapter in the history of psychosurgery in which his technique was so enthusiastically received that psychosurgery was at times abused and indiscriminately applied. Complications arose related to its practice by unqualified practitioners in unsterile conditions using crude instruments with poor anesthesia care and perioperative monitoring. Furthermore, the morbidity and neurologic sequelae from the procedure became more evident over time, patient selection criteria were questioned, and the procedure’s actual efficacy was questioned more criticially.
Freeman’s procedure (which also came to be known as “the icepick lobotomy” [20]) quickly fell out of favor with the neurosurgical establishment, including with Watts, leading the two former collaborators to part ways soon thereafter [13]. Nevertheless, given the public health crisis regarding the mass management of psychiatric illness in the population before the introduction of effective psychotropic medications with chlorpromazine in 1954, the Freeman lobotomy continued to be widely performed, with an estimated 60,000 procedures performed between 1936 and 1956 [15]. However, with the rejection of Freeman’s procedure by neurosurgeons, and the continuing social recognition of its excessively exuberant application, along with the availability of effective neuroleptic drugs, the notorious era of the Freeman frontal lobotomy mostly came to an end in the late 1950s [1, 8, 13, 21].
At the same time that Freeman was overzealously promoting his transorbital leukotomy, more responsible practitioners of the day were employing a safer and more restricted approach to psychosurgery [13]. William Beecher Scoville, a neurosurgical contemporary of Freeman, was the first to introduce the concept of minimalism in psychosurgery, which very much diverged from Freeman’s industrial scale concept. The idea was to maximize therapeutic efficacy, while minimizing unnecessary morbidity and undesirable sequelae to the patient. In the late 1940s, Scoville developed the technique of orbital undercutting to selectively ablate orbitofrontal cortex in a more anatomically localized manner through bifrontal trephinations [13, 22, 23]. Other more precise open surgical procedures were also described during this time period and included bilateral inferior leucotomy, bimedial frontal leucotomy and anterior cingulectomies, all guided by the most current understanding at that time, of the neuroanatomic pathways underlying psychiatric illness.
The goal of making small, accurate and effective lesions in psychiatric patients without serious mortality and morbidity was the major impetus for the development of stereotactic neurosurgery [10, 13, 20]. All intracranial psychosurgery today stems from the stereotactic school, including both contemporary ablative techniques and deep brain stimulation techniques [20].
In stereotactic neurosurgery, the brain is referenced against a fixed frame of reference, assigning a specific coordinate system to define any point in the brain in Cartesian three dimensional space [24]. Stereotactically guided neurosurgical procedures were first devised for use in humans in 1947 by Ernst Spiegel and Henry Wycis, who designed a stereotactic system referenced by X-ray ventriculography to perform dorsomedial thalamotomy , representing the first attempt at a minimally invasive subcortical ablative procedure [13, 24]. Various other stereotactic systems were developed for clinical use and lesioning of deep brain structures for treatment of psychiatric disease began. Jean Talairach first described ablation in the anterior internal capsule to treat psychiatric disease in 1949 [25, 26], and Leksell began using his stereotactic system to further study and develop methods to perform minimally invasive anterior capsulotomy to treat a variety of psychiatric disorders .
Soon after introducing his stereotactic frame in 1951, Leksell envisioned the concept of radiosurgery to improve upon the minimally invasive nature of stereotactic procedures [25]. Open stereotactic procedures still required a scalp incision, boney access through the cranial vault and a penetrating needle trajectory through the brain paryenchyma to the target, but Leksell imagined that sharply focused radiation beams from external radiation sources could summate at the stereotactic target, to create the desired lesion completely non-invasively. Leksell’s concept of stereotactic radiosurgery laid the groundwork for the eventual development of the gamma-knife technology, which became commercially available in the 1980s [13]. In the present day, both “traditional open” stereotactic surgery and minimally invasive stereotactic radiosurgery are pursued as options in psychosurgery. In particular, gamma knife is being investigated for carrying out anterior capsulotomy in a double blind randomized control trial in Brazil, the first study of its kind for a psychiatric lesion procedure [8, 26, 27].
The mortality and morbidity associated with the imprecise methods and risky approaches of the Freeman lobotomy era and other earlier psychosurgical practices were largely erased with the advent of modern stereotactic techniques. A variety of targets were subsequently explored including the anterior cingulate gyrus, anterior limb of the internal capsule and the subcaudate regions. Much of our best contemporary understanding of the neurophysiologic basis of psychiatric disease focuses on the limbic system and its neural circuitry connecting with the frontal lobes and basal ganglia . Consequently, nearly all current psychosurgical interventions place their target in one or more aspect of the limbic system and its connections.
5.2 Relevant Anatomy and Physiology
An understanding of the frontal-subcortical circuitry involved in psychiatric diseases is necessary for understanding target selection in psychosurgical lesioning. Executive dysfunction, apathy, and impulsivity are hallmarks of frontal-subfrontal circuit dysfunction, and the psychiatric illnesses treated by psychosurgery, such as depression and obsessive-compulsive disorder (OCD), are associated with dysfunctional neural substrates in these circuits as well [28].
To understand the importance of the frontal-subcortical circuits of interest, a review of subcortical targets is essential. All three circuits connect through the basal ganglia . The basal ganglia are a group of nuclei situated at the base of the forebrain and include the striatum (caudate nucleus and putamen), the globus pallidus, the substantia nigra, the nucleus accumbens , and the subthalamic nucleus, each with its own complex internal anatomical and neurochemical organization. These nuclei are involved in varied functions, including voluntary motor control, procedural learning, including those involved in behavior and habits, eye movements, as well as cognitive and emotional functions [29]. The most unified, current theory relating the varied nuclei suggests that they are all involved in action selection or the decision of which of several possible behavioral actions to take at any given time [30]. Experimental evidence indicates the basal ganglia inhibit a number of motor systems, wherein discontinuation of this inhibition allows a given motor system to become active. The action selections by the basal ganglia are heavily influenced by input from the prefrontal circuitry described [31, 32]. Lesions in the circuitry connecting the frontal lobes to the basal ganglia can generate disorders closely resembling frontal lobe lesions. These “striatal” syndromes have not been extensively studied, but disinhibition and executive dysfunction are documented consequences [32].
Lesions in basal ganglia structures are implicated as the major substrate for a number of neurological conditions. Movement disorders, including Parkinson’s and Huntington’s disease, are associated with the degeneration of dopamine -producing cells in the substantia nigra pars compacta and damage to the striatum, respectively [30, 33]. Parkinson’s patients exhibit depression, dementia and confusional states. Dysfunction in the basal ganglia are also implicated in disorders of behavior control, including Tourette’s syndrome, hemiballismus, and obsessive-compulsive disorder (OCD) [34]. Additionally, positron emission tomography studies of patients with OCD show increased metabolic function in the frontal lobes, cingulum, and caudate nucleus [34].
Arguably, more critical to the success of psychosurgery are the functions and neuroanatomy of the limbic system. The system was named by Paul Broca, with limbic originating from the Latin limbus, meaning “border”, as it lies between two functionally different portions of the brain; the neocortex, which mediates external stimuli, and the brainstem, which mediates internal stimuli [35, 36]. The limbic lobe is an intricate set of brain structures, broadly consisting of the arcuate convolution of the cingulate and parahippocampal gyri of the medial aspect of the cerebral hemispheres [37, 38]. These arcuate structures are situated around the thalamus bilaterally, composed of a conglomerate of structures from the telencephalon, diencephalon, and mesencephalon. The limbic system also includes the olfactory bulbs, hippocampus, amygdala, anterior thalamic nuclei, fornix, column of fornix, mammillary body, septum pellucidum, habenular commissure, cingulate gyrus, parahippocampal gyrus, limbic cortex and limbic midbrain regions [39]. These structures have myriad functional capacities, including memory, emotion, behavior, motivation, long-term memory, and olfaction. It is best known as the central system for human emotion and memory formation, and includes the famed Papez circuit [37–39].
The location and role of the limbic system as mediator between internal and external stimuli as reported by the neocortex and primitive brain allow it to regulate the complex processes of subjective, somatic, visceral, and behavioral stimuli integration and modulation necessary for emotional experience. Reciprocal connections converge in the amygdala, symmetric almond shaped nuclei positioned at the anterior end of the hippocampi, which are critically important in emotional processing and memory [40]. Lesions in the amygdala in rhesus monkeys results in the Kluver-Bucy syndrome, characterized by limited emotional arousal regardless of presence or absence of threatening stimuli, hypersexuality, hyperorality, hyperphagia, amnesia and agnosia [41].
The origins of the frontal-subcortical circuits are all located within the frontal lobe. A simplified model of frontal lobe circuitry consists of five major pathways. Two of the pathways are the motor and oculomotor circuits, which originate in the frontal eye fields and drive eye movement, but will not be discussed in detail here. The remaining three circuits are behaviorally relevant with origins in the prefrontal cortex; a dorsolateral prefrontal circuit, which is regarded as the mediator of executive function; the anterior cingulated circuit, which governs motivational functions; and the orbitofrontal circuit , which has two subdivisions: the lateral and medial [28]. All five circuits share common structures and are both parallel and contiguous, yet they are distinctly partitioned anatomically. Brain regions linked by these circuits are functionally related; those governing limbic function synapse heavily with other limbic structures and those related to executive function have diverse connections to higher cortical areas involved in cognition [42–45].
The dorsolateral prefrontal circuit begins in the dorsolateral region of the frontal lobe in Broadmann’s areas 9 and 10. Neurons from this locus project to the head of the dorsolateral head of the caudate nucleus and medial putamen of the basal ganglia , and the projections communicate information regarding “executive” function [45]. Executive function integrates anticipation, goal selection, planning, observation and incorporation of external and internal feedback in task performance [46]. The clinicopathological correlation between lesions in this circuit and psychiatric illness is elucidated by dorsolateral prefrontal syndrome. Individuals affected by this condition have defects in executive function marked by marked perseveration, often measured with the Wisconsin Card Sort Test, designed to gauge test-takers’ ability to shift strategies [47]. Other features include impaired verbal and design fluency, memory search strategy, motor programming, and organizational and constructional strategies during learning and copying tasks. As with all frontal circuits, similar syndromic features have been reported with lesions to efferent basal ganglia regions [48, 49]. Psychiatric syndromes including schizophrenia, depression and OCD display impaired executive function, suggesting that this circuit is involved [28].
The orbitofrontal circuit consists of the medial and lateral divisions. The lateral division has its origin in the lateral orbital gyrus of Brodmann’s area 11 as well as the medial inferior frontal gyrus of areas 10 and 47 [50]. Lateral division projections lead to the ventromedial caudate [51]. The medial division originates in the inferomedial prefrontal cortex in the gyrus rectus and medial orbital gyrus of Brodmann’s area 11, projecting to the medial nucleus accumbens [50, 52]. As the orbitofrontal cortex is considered to be the neocortical representation of the limbic system, it functions in calculating appropriate strategy, timing, and place for behavioral responses to environmental stimuli [53]. Thus, lesions in the circuit sever the frontal monitoring and modulation mechanisms necessary to curb impulses from the limbic system, resulting in orbitofrontal syndrome with characteristic disinhibition, lability, and irritability [54]. Affected patients appear tactless and may exhibit inappropriate jocularity, improper sexual remarks or gestures. Patients may also display transient irritable outbursts, inattention, distractibility, and increased motor activity along with hypomania or mania [55, 56]. Extreme changes in personality are typically in the setting of bilateral insults to the orbitofrontal regions, however unilateral lesions result in similar changes with lesions to the right hemisphere demonstrating disproportionately greater loss of inhibition [57, 58]. Similarly, patients with lesions to the ventral caudate have been documented exhibiting disinhibition, euphoria, impulsivity, and inappropriate social behaviors, showing the reciprocal relationship between the efferent and afferent ends of the circuit [59].
The anterior cingulate circuit originates in the anterior cingulate gyrus (Broadmann’s area 24) and projects to the ventral striatum, including the ventromedial caudate, ventral putamen, nucleus accumbens , and olfactory tubercle, all of which are referred to collectively as the limbic striatum [60]. Anterior cingulate syndrome at its worst can result in profound apathy and akinetic mutism, a waking state of profound apathy, absence of motor and psychic initiative with a lack of spontaneous movement; indifference to pain, thirst, and hunger; absent verbalization; and failure to respond to commands [61, 62]. This condition has been documented in bilateral lesions to the anterior cingulate cortex and vascular and neoplastic lesions involving the ventral striatum, as well as and obstructive hydrocephalus in the region of the third ventricle and [28, 61]. A less severe form of this condition termed “abulia” involves similar psychomotor qualities, including lack of spontaneity, apathy, and decreased speech and movement. These behavioral syndromes highlight the importance of the frontal lobe pathways in regulating executive and social function as well as mood and motivation [61, 63].
5.3 Contemporary Psychosurgery
5.3.1 Established Psychosurgical Procedures and Indications in the Modern Era
With the application of stereotactic techniques in psychosurgery, several minimally invasive techniques were developed to treat psychiatric illness with impressive results. There are currently four accepted psychosurgical techniques, each with varied targets but all performed bilaterally under stereotactic guidance for optimal precision in targeting. They have evolved to a level of sophistication and critical appraisal far beyond the primitive operations performed by non-expert physicians in the Freeman era of frontal lobotomy.
Anterior Cingulotomy In 1947, Fulton published evidence that stimulating the anterior cingulate in monkeys resulted in significantly less fearful but more aggressive subjects with autonomic responses that mimicked those of heightened emotion [59]. Fulton postulated that modulation of the anterior cingulated cortex could mitigate psychiatric disease, and in the early 1950s, a British group first performed the procedure [64]. The procedure was popularized by the American surgeon Ballantine in the 1960s, who subsequently conducted research over decades [65].
The procedure is currently employed to treat refractory major affective disorder, severe chronic pain, chronic anxiety states and OCD [66]. The cingulate plays a crucial role in the Papez circuit, and OCD studies have shown increased metabolism in the anterior cingulate in individuals affected by the disorder [37, 38, 67]. The procedure is not performed until patients are accepted through a rigorous multidisciplinary screen, after which bilateral stereotactic thermocoagulation lesions are placed bilaterally in the cingulum [68]. Retrospective studies have shown that 25–30 % of medically refractory OCD patients were considered improved post-operatively, where treatment success was considered to be improvement of 35 % or greater on the Yale-Brown OCD Scale [69]. Furthermore, the study highlighted the relative safety of the procedure: no surgery-related deaths were reported, the only complications reported in the post-operative period were seizures responsive to medication. In the first prospective study, a similar success rate of 25–30 % for medically-refractory OCD patients was reported to achieve the same level of improvement [69]. Another prospective study showed 32 % met criteria for response to treatment and an additional 14 % were found to be partial responders at an average of 32 months follow-up. Complications were again limited: one patient reported increased urinary incontinence, one had drug responsive seizures, and one committed suicide. The most recent study of response to anterior cingulotomy by those with medically refractory OCD showed full response (35 % or more severity reduction on the Yale-Brown Scale) rates of 47 % of full response and 22 % partial response (24–35 % reduction on the Yale-Brown Scale) at a mean follow-up of 63.8 months, the most impressive results yet [70]. Additionally, comorbid major depressive disorder severity decreased by 17 % in the same study.
Anterior Capsulotomy This technique was developed by Talairach in France in the 1940s. Indications for this procedure initially included a wide range of conditions, including schizophrenia, depression, chronic anxiety and obsessional neurosis [66]. It uses thermocoagulation or gamma knife to lesion the fronto-limbic fibers that pass between caudate and putamen in the internal capsule of the basal ganglia [71]. When Leksell initially operated on patients with psychiatric disease, he reported a 50 % satisfactory response with “obsessional neurosis” and 48 % with depression, while lower rates of 20 and 14 % satisfactory response were observed with “anxiety neurosis” and schizophrenia, respectively [72]. When compared to anterior cingulotomy , studies have reported a higher index of efficacy with anterior capsulotomy , and success rates as high as 70 % have been published. Unfortunately, the procedure is also associated with the highest frequency of complications and morbidity, most notably weight gain, confusion, nocturnal incontinence and cognitive dysfunction [72].
Subcaudate Tractotomy Designed in England by Geoffrey Knight in 1964, this approach targets fibers from the frontal lobes to subcortical structures in the limbic system, including the amygdala [73]. The procedure was created as a method of reducing the extent of frontal lobe lesioning, and has been more popular in the UK than the US since its advent. Like the anterior cingulotomy , the procedure is indicated for affective and anxiety disorders, including severe, refractory OCD and depression. However, it is not indicated for cognitive disorders. The precise target of the subcaudate tractotomy is the substantia innominata , directly inferior and adjacent to the head of the caudate nucleus [10]. Originally, the procedure involved the placement of radioactive seeds in the frontal lobes, but is currently performed with stereotactic thermocoagulation . In the first major assessment of the efficacy of the procedure in the 1970s, over 60 % of patients with depression or anxiety showed improvement with nearly 50 % of patients affected by obsessive-compulsive disorder showing improvement [74]. A subsequent retrospective study reported a response rate of 34 % in patients undergoing the procedure from 1979 to 1991 [74, 75]. Like the anterior capsulotomy procedure, these high rates of efficacy come at a higher cost than is associated with anterior cingulotomy . Approximately 1.6 % of patients suffered from seizures after surgery , and just under 7 % reported negative personality changes post-operatively [74]. However, a psychometric study performed on 23 patients pre-operatively and at two intervals post-operatively showed no major cognitive deficits [76].
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
