Chapter 119 Deep Brain Stimulation for Intractable Psychiatric Illness

Deep brain stimulation (DBS) has become the gold standard for the surgical treatment of movement disorders such as Parkinson’s disease, tremor, and dystonia. It is estimated that more than 60,000 people worldwide will have had DBS hardware implanted by 2010. The widespread adoption of DBS has been largely due to the advantages it has over its predecessors, the so-called lesioning procedures (pallidotomy and thalamotomy). Although these procedures were widely studied and generally safe, they were destructive, irreversible, and nonadjustable. Lesioning also had a higher complication rate when performed bilaterally, even though bilateral treatment was desirable in many patients for optimal outcome. With the development of DBS, surgical therapy for movement disorders took an evolutionary step forward. Thanks to the nondestructive nature of electrode implantation and the ability to alter multiple stimulation parameters via an implanted pulse generator, treatment became adjustable and reversible by merely turning the stimulation off. Moreover, clinicians found it safe to treat patients with bilateral stimulation. In recent years, there has been tremendous interest in the application of DBS to treat patients with severe psychiatric illness, largely due to the perceived advantages of stimulation over lesioning for these disorders. Modern-day surgery for intractable psychiatric illness is a fast-moving specialty with many studies under way at the time of this writing, which makes it a challenging topic to discuss in a textbook chapter. We therefore focus on the history, development, and rationale for the use of DBS in several psychiatric disorders to date, with some views on what the future may hold.

Limited reports of neurosurgical procedures for derangement in behavior and thinking date back to the late 1800s.¹ However, the true birth of psychosurgery was not until 1935, when Moniz and Lima developed the frontal leucotomy. Inspired by frontal disconnection studies done at Yale University by Fulton and Jacobsen, which reduced agitation in primates, Moniz and Lima performed a series of bur hole–based frontal lesioning procedures starting in November of that year. This involved placing an instrument through several bur holes and making sweeping motions in roughly a coronal plane to “disconnect” the frontal lobe from the rest of the brain. Shortly thereafter, Freeman, an American neurologist, teamed up with Watts, a neurosurgeon, and in 1936 started performing a similar procedure, which the pair called the frontal lobotomy. These procedures were introduced at a time when there were no medical treatments available; patients were either permanently institutionalized or treated with “shock therapy” using electrical current, insulin, or metrazol. By the end of the 1930s, there were more than 400,000 psychiatric inpatients in the United States, occupying more than 50% of the hospital beds in the country.¹ In retrospect, these procedures were crude and imprecise, but given the technology of the day and the desperation of many psychiatrists to find effective treatments for their patients, the frontal lobotomy gained support by many practitioners. Freeman was an outgoing and vocal advocate for the procedure and in some ways was as much a showman as he was a physician. As time went on, he became increasingly convinced that the procedures could be done in an office by non-neurosurgeons; he developed the transorbital approach, or the so-called ice-pick procedure, which led to the dissolution of his professional collaboration with Watts. Even after the introduction of Thorazine (the first truly effective antipsychotic agent) in 1954, Freeman continued to champion what he believed were the merits of frontal lobotomy, despite a clear movement of the rest of his profession away from the procedure over safety concerns. What followed was a backlash against lobotomy in general and Freeman in particular.

Despite this negative sentiment toward surgery, several centers around the world continued to perform and refine lesional procedures. The development of frame-based stereotaxy for human surgery in the 1940s by Spiegel and Wycis,^1a along with the development of stereotactic atlases, meant surgeons could make discrete lesions in the brain with far more accuracy. Procedures such as cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy came into their own right as legitimate treatments for medically refractory illness. At the same time, the field of psychiatry continued to mature, with better characterizations and definitions of the various disorders being treated. The recent resurgence in interest in surgery for psychiatric disorders was brought about largely by the development of DBS in the 1990s. In addition, the development of functional imaging and biochemical analysis allowed researchers to discover brain areas that appear to be involved in diseases like obsessive-compulsive disorder (OCD) and major depression, and as we show, some of this work has translated directly into targets for DBS. Finally, there has been a definite shift in the last decade toward viewing these illnesses as systems-level disorders of specific neuronal circuits, subcortical and cortical in nature. This view is analogous to Parkinson’s disease, where a circuit abnormality leads to movement disorder. Psychiatric disorders appear to also have underlying neuronal circuits, where abnormalities manifest as a limbic disorder. In this vein, the term “limbic disorders surgery” may be a more accurate term for what was previously referred to as “psychosurgery.”

Given that specific circuits seem to underlie these disorders, one significant challenge is deciding exactly where anatomically to place a DBS electrode. The use of DBS in Parkinson’s disease benefited from the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model that allowed researchers to gain insight into the underlying motor circuits in that disorder and predict the outcome of therapeutic stimulation in humans. Even with this model, DBS target selection in PD and other disorders such as essential tremor was based in part on historical experience with lesioning procedures such as pallidotomy and thalamotomy. The limbic disorders do not yet have robust animal models that can be used to gain insight into possible target selection. Instead, targets for DBS have been selected based on functional imaging, observations made while using DBS to treat other disorders, and historical lesioning experience.

Obsessive-Compulsive Disorder

OCD is a challenging illness in which unwanted and intrusive thoughts (obsessions) lead to repetitive and even ritualistic behaviors (compulsions). The obsessions vary and can be based on a variety of things, such as cleanliness, symmetry, or concerns about safety, security, or throwing away something valuable. The subsequent compulsions that the patients engage in are directly related to their obsessions and include things such as cleaning, arranging, checking, and hoarding. They can be so consuming that patients become physically unable to engage in normal activity or can even injure themselves. OCD frequently occurs in combination with other psychiatric disorders such as Tourette syndrome (TS), although comorbid depression and other conditions are common as well. The pathophysiology is not understood, although abnormalities in serotonin have been implicated as a potential contributor. The most effective medical treatment is administration of selective serotonin reuptake inhibitors (SSRIs), which further supports this theory. Often, combinations of SSRIs with other agents are required. Cognitive behavioral therapy (CBT) is also frequently employed, the goal of which is to expose the patients in a controlled manner to things that trigger their symptoms. Surgery has been historically reserved for only those patients with the severest symptoms and who are refractory to medical and CBT. Disease severity in OCD is determined by a clinical rating scale, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). In general, it is accepted that any treatment modality must result in a 25% to 35% reduction in the Y-BOCS to be considered effective.

There is a long history of treating OCD with surgical lesioning. Although multiple areas have been explored, including the cingulate gyrus, many have focused on the anterior limb of the internal capsule, the target for the so-called capsulotomy. More recently, the term ventral capsule/ventral striatum (VC/VS) has been coined to describe the region including the ventral anterior internal capsule and the nucleus accumbens (NAcc), which has been implicated as a potential target in all three psychiatric disorders currently treated with DBS. The definition of this region evolved largely because surgical trials in OCD showed that lesioning or stimulating more ventrally and posteriorly in the capsule (or near the NAcc) resulted in better outcomes—in the case of DBS, with lower stimulation amplitudes (Fig. 119-1). The NAcc itself is believed to receive input from multiple areas, including the orbitofrontal cortex, amygdala, and caudate, and have projections to multiple areas, including the cingulate cortex, striatum, and frontal areas.

FIGURE 119-1 Preoperative targeting MRI scans and postoperative skull x-ray of a patient undergoing ventral capsule/ventral striatum DBS implantation for OCD or TRD. A, An axial T1-weighted image at the level of the AC-PC plane. The target is set at the junction of the anterior limb of the internal capsule and the AC (red dot), with the goal of over-shooting slightly so the gap between contact 0 and contact 1 is at the level of the AC. B, A coronal T1-weighted MRI at the level of the AC.Note that the approach angle in the coronal plane should be varied from patient to patient such that the distal portion of the lead (i.e., the contact array) runs down the long axis of the internal capsule. C, A postoperative lateral skull x-ray. Note the wide spaced Model 3391 electrodes used in these patients.

The first published series of OCD patients treated with DBS was in 2003 by a group of researchers from Belgium, who stimulated the anterior limb of the internal capsule in six patients using a target similar to that used for capsulotomy.² In stereotactic space relative to the midpoint between the anterior commissure (AC) and the posterior commissure (PC), the target was 13 to 14 mm lateral, 3.5 mm anterior in the anteroposterior dimension, and at a depth of 0 mm (at the AC-PC plane). A widely spaced electrode array was used to span the length of the capsule (Medtronic model 3391, 3-mm-long electrodes with 4-mm interelectrode spacing). All patients entered a screening phase for several weeks to several months after surgery to determine optimal stimulation parameters. Four of the patients went on to a blinded crossover evaluation phase; two other patients formally enrolled, and two anecdotal patients were described in an addendum to the original paper.² The mean Y-BOCS score with stimulation was 19.8 ± 8.0 (considered “moderate severity”), compared to 32.3 ± 3.9 (“extreme severity”) without stimulation. Relatively high stimulation parameters were needed to achieve benefit, with pulse generator replacements required every 5 to 12 months. A concern related to the short battery life was a severe, acute recurrence of OCD symptoms if there was an abrupt cessation of stimulation. Prophylactic battery changes were recommended to avoid this complication. Several groups believed that the high stimulation parameters and use of ventral active contacts in this study might be stimulating the NAcc.^3,4 A subsequent multicenter study in the United States implanted 10 patients in the VC/VS.⁴ Eight patients completed the study with a 36-month follow-up. Two patients had less than a 25% improvement in their Y-BOCS scores and were considered nonresponders, but the six others were responders, with two patients showing improvement between 25% and 35% and four showing improvement greater than 35%.

The combined European and American experience with DBS in the VC/VS led to a Humanitarian Device Exemption (HDE) approval by the U.S. Food and Drug Administration in early 2009. Although the HDE requires that surgeons obtain Institutional Review Board approval from the hospital where surgeries will be performed and the approval does not guarantee that insurance carriers will reimburse for the procedures, the approval was nevertheless an important event in modern-day limbic disorders surgery in the United States. The HDE approval is specific to the VC/VS, and although this is the most described target in the literature, the optimal target for intervention in OCD is still not known. For example, a double-blind, crossover study in France of associative-limbic STN territory stimulation versus sham stimulation in 16 OCD patients showed lower Y-BOCS scores with active treatment (19 ± 8) than with sham (28 ± 7) stimulation (P = 0.01)—and at significantly lower stimulation amplitude (2.0 ± 0.8 vs. 7.6V in Nuttin’s original series).⁵

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