The introduction of innovative biomedical technologies, as well as enhanced neuropharmacologic therapies, has provided the mental health community with the ability to treat mental health patients with quality care. Understanding the neurobiological basis of psychiatric disease may afford us with the ability to further our comprehension of the underlying mechanisms in these diseases, and thereby develop improved methodologies of treatment. A very limited percentage of patients are eligible for neurosurgical intervention to treat their brain-based mental disorder. This extreme practice of psychosurgery illustrates how the biomedical community identifies neuro-substrate regions of the brain which may account for specific psychiatric disorders, and subsequently modify them in an attempt to alter behavior.

Chaotic. Extreme. Barbaric. Irresponsible.

These are the descriptions which the critic may impose on this art of medicine. Yet, the neuroscience community understands that every true medical breakthrough is met with its initial skepticism and resistance. And, if we are to fight the war on mental health with our complete repertoire of therapeutic interventions, than a comprehensive analysis on the evolution of this risky treatment option is warranted.

Our modern understanding of functional neuroanatomy, combined with advances in stereotactic technology and functional imaging, creates a setting in which neurosurgery may offer a minimally invasive and highly selective treatment option for a variety of psychiatric illnesses.

Currently, the accepted therapeutic approach to most psychiatric disease involves a combination of well-supervised psychotherapy, pharmacological intervention and even in some instances, electroconvulsive therapy.  However, despite these modern treatment methods, many patients fail to respond to treatments sufficiently, and unfortunately remain severely disabled by their disease.

Consequently, the performance of surgery to control the haunting symptoms of a disturbed mind may very well be a viable option in the future of psychiatric treatment.


Walter Freeman, The Lobotomist. 

Technical Neurosurgical Procedures for Behavioral- Based Disorders

    The rich history and evolution of psychosurgery has finally lead to the acceptance of 4 commonly employed neurosurgical procedures used to treat psychiatric disease. Although they each differ in their technique and methodology, each procedure is performed bilaterally and under stereotactic conditions, which allows for precise lesioning of the targeted structures.

Subcaudate Tractotomy

This procedure was designed in England by Geoffrey Knight in 1964 as a method of minimizing frontal lobe lesioning by interrupting fibers from the frontal lobes to subcortical structures such as the amygdala.  The site of the lesion is the substantia innominata, just below the head of the caudate nucleus.  In a study of 208 patients in the 1970s, approximately 2/3 of patients with depression or anxiety had post-operative improvement, while 50% of obsessive patients also demonstrated improvemen. Nine female patients with bipolar disorder were studied 4 years post operation, and 5 demonstrated marked improvement, while 4 showed mild improvement.


Anterior Cingulotomy 

The anterior cingulum was first suggested as a surgical target for the treatment of psychiatric disease in 1947. This was based on evidence that stimulation of the anterior cingulum in monkeys produced autonomic responses associated with emotion. Lesions in this region significantly resulted in less fearful and more aggressive animal. This procedure is currently used to treat refractory major affective disorder, severe chronic pain, chronic anxiety states or OCD. The cingulate cortex is an important structure in the anatomical-behavioral circuit which Papez outlined. MRI guided stereotactic techniques are used to properly isolate target coordinates, and lesions are created via thermocoagulation. The day after surgery, a post-operative MRI scan is obtained to visualize the placement and extent of the lesions.
Limbic Leucotomy 

Introduced in 1973 by  Dr. Nita Mitchell-Heggs and Dr. Desmond Kelly, this procedure is essentially the combination of stereotactic lesions created in the subcaudate tractotomy and anterior cingulotomy in order to disconnect orbital-frontal-thalamic pathways. The lesions are created using a either cryoprobe or thermocoagulation and up to 14 cryogenic lesions are made in the brain. Price et al., has demonstrated 36–50% of patients with major depressive disorder and OCD showed improvements with little adverse side effects from the procedure, while 4/5 patients who were engaged in self mutilation showed sustained reduction in self-injurious behavior post operative follow-up at 32 month.


Anterior Capsulotomy 

This procedure was designed in the late 1940s. Due to the innovation of the Swedish neurosurgeon Leksell, it currently uses thermocoagulation or gamma-knife stereotaxis to lesion the fronto-limbic fibers that pass in the internal capsule as it courses between the caudate and putamen nuclei of the basal ganglia.  Clinical indications for capsulotomy initially included schizophrenia, depression, chronic anxiety states and obsessional neurosis. Leskell initially operated on 116 patients with a variety of psychiatric disorders; 50% of patients with obsessional neurosis and 48% of depressed patients had a satisfactory response, while 20% of patients with anxiety neurosis and 14% of patients with schizophrenia also showed improvement.

Cutting Specific Brain Regions: How Do Surgeons Know? 


Neurosurgeons must know which neuroanatomical region within the brain to lesion or ablate when attempting to alleviate symptoms of a severe mood disorder. Mayberg et al. published functional neuroimaging studies which confirm a consistent involvement of the subgenual cingulate (Cg 25) in the modulation of negative mood states, such as depression. This study further reported a decrease in Cg 25 activity in patients who respond positively to various antidepressant treatments such as SSRIs, ECT and ablative surgery. Further evidence for the labeling of Cg 25 as a culprit in the depression pathway is the fact that it is connected to the brainstem, hypothalamus and insula, which have all been implicated to be disturbed during a depressed episode. Additionally, studies link Cg 25 to orbitofrontal, medial prefrontal, and part of the anterior and posterior cingulate cortices, which are all involved in the regulation of homeostatic and autonomic functioning of learning, memory and mood–all core behaviors altered in a depressed state. Long term electrical stimulation of basal ganglia structures, such as the globus pallidus internus and subthalamic nucleus, are achieved by an implantable electrode that is connected to a pulse generator within the chest of the patient. This technique, before being used on psychiatric patients, has been found to ameliorate bradykinesia, tremor, and muscle rigidity. The patients are kept awake throughout the procedure in order for them to describe any changes in the language or speech capabilities; the only drug administered is a local anesthetic. Mayberg et al. tested the hypothesis that the use of deep brain stimulation can modulate its pathological metabolic activity in the known neural circuitry being altered in the brains of treatment-resistant depressed patients. The neurosurgeons used MR-imaging to place the DBS electrodes within the subgenual cingulate and used a frequency parameter of 10–130 Hz, and the voltage of the electrodes was changes every 30 seconds with a 1.0V increase. After 5 months of the DBS electrode therapy, 4/6 (66%) of the patients met the antidepressant response positive threshold. Mayberg et al. used PET imaging to characterize the activity in the brain networks involved in treatment-resistant depression. These results provided a quantitative measure of brain changes which are associated with DBS stimulation and their correlating positive psychological effects on depressed patients. In comparing PET images from 6 patients to control data of the same gender and age group, Mayberg et al. demonstrate that depressed patients show a unique pattern of elevated Cg25 blood flow at pretreatment baseline. Furthermore, a hyperactive Cg25 and hypoactive prefrontal cortex was seen in DBS responders and nonresponders.

The Future of Biotechnology and Surgical Intervention for Mental Health Treatment


Neurosurgeons, psychiatrists, biomedical engineers, and pharmaceutical companies are only a few departments which need to be heavily funded in order to provide care for the mentally-ill community. Neurosurgical treatment for psychiatric disorders has a long and controversial history. From the Stone Age use of trephining to release the demons of the spirit to the millimeter accuracy of stereotactic instruments currently used in the operating room, psychosurgery has had great support and intense scrutiny. Today, psychosurgery is mastered in a minimally invasive and highly selective manner that is performed only for a few patients with severe and treatment-refractive psychiatric disorders. Despite remarkable advances in pharmacotherapy, the side effects of many drugs can be debilitating, and a substantial number of patients treated with drugs and behavioral therapy either do not improve or relapse. It is unfortunate that the prognoses of treatment resistant affective disorders are quite poor, leaving patients and their families left with relatively no options and extreme emotional burden. Advances within the scientific community, such as functional neuroimaging, as well as the economic pressure to decrease the costs of caring for ill patients, may provide an opportunity for psychosurgery to become a more attractive option for the treatment of psychiatric diseases in the future. The modern procedures described herein are rather safe, with an extremely low surgical mortality rate. Further, it is clear from retrospective neuropsychological assessments that patients initially exhibiting refractory conditions showed gradual, if not significant, improvement via psychosurgical intervention. In order to develop a stronger future for neurosurgical intervention in the treatment of psychiatric disease, research must undergo an attempt to further delineate anatomic substrates for emotional states. The application of modern functional imaging techniques is surely assisting in this avenue. Although the innovations of Paper were significant, they are insufficient if we are to treat patients on a common basis with surgical intervention. The scientific community must develop concise data as to the anatomical regions in the brain which are specifically responsible for emotional and cognitive states of mind. It is also important that the biomedical community begins to innovate our interventional approaches to attacking and healing the brain via surgical instrumentation. Theoretically, we can begin to hypothesize that psychosurgery need not be limited to destroying dysfunctional brain tissue. It is conceivable that in the future we may begin to incorporate the advances taking place in neuroengineering in order to not only decrease activity within a defected area of the brain, but to also increase activity. Drug secreting capsules, neuromodulator pumps, and the implantation of genetically engineered vectors for gene delivery may all be methods we begin to implement in the foreseeable future. Overall, our approach to treating patients with refractory neuropsychiatric disease needs improvement which will come with innovative experimentation on the human brain in the next generation.

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