Deep Brain Stimulation—A Treatment for Neuropsychiatric Disorders?

TUCSON—Knowledge and experience gained from treating movement disorders with deep brain stimulation are now being leveraged to determine whether symptoms in patients with obsessive-compulsive disorder (OCD), Tourette’s syndrome, and depression can be improved with this technique.

“The premise is that these disorders are focal disturbances in neuronal function,” said Andres M. Lozano, MD, PhD, FRCSC, FACS at the 18th Annual Meeting of the American Neuropsychiatric Association. “They are relatively small groups of neurons that are dysfunctioning in circuits and this dysfunction is transmitted through the connections throughout the entire brain, so that the activities of a few are being heard and resonate throughout the brain.”

APPLIED SCIENCE

Using modern techniques, it is possible to pinpoint these disturbances, breach the neuronal elements, “smoke them out,” and neutralize disruptive behavior. “Deep brain stimulation is a means of either knocking down or knocking out pathological function in circuits, or driving activity in circuits that are underperforming,” said Dr. Lozano, a Senior Scientist in the Division of Brain Imaging and Behaviour Systems – Neuroscience at Toronto Western Research Institute.

The FDA approved deep brain stimulation in 1997 for controlling tremor in patients with essential tremor or Parkinson’s disease (unilateral implantation only). The treatment was approved for Parkinson’s disease in 2002 (bilateral implantation) and for primary dystonia in 2003.

More than 35,000 patients with Parkinson’s disease have been treated with deep brain stimulation, yet this therapy remains underutilized: An estimated 10% to 15% of the 4.5 million patients with Parkinson’s disease are candidates.

This underscores that “despite our best available therapies,” many patients continue to suffer from neurologic and psychiatric diseases, Dr. Lozano said. Enhanced brain imaging and an increased understanding of pathophysiology have led to “a better idea of where we need to go in the brain, where we need to intervene,” he added. “We also have better neurosurgical techniques and, of course, we have advances in molecular biology and biotechnology. All these things are now coming together at this moment in time in what is a new field of intervention in the brain using deep brain stimulation.”

He described a patient with stimulators implanted in the subthalamic nucleus who has a tremor that recurs as soon as the stimulators are turned off. “The difference between her having tremor and not is roughly 25,000 neurons in the subthalamic nucleus firing at the tremor frequency. The importance of this is to emphasize that you have to be in the proper area of the motor territory.”

If stimulation spreads internally into the hypothalamus, “there have been reports of aggressive behavior induced by intraoperative stimulation in the vicinity of the subthalamic nucleus, thought to be related to the spread of the current to the hypothalamus. There have also been acute depression and anxiety induced by stimulation in the vicinity of the substantia nigra pars reticulata; there have also been reports of euphoria and laughter—mirthful laughter—reported by stimulation in the subthalamic nucleus.”

“Because the subthalamic nucleus is rather small—it has roughly 330,000 neurons—it’s quite difficult to only be in the motor territory without having some spillover into the cognitive and limbic territory, so we often, if the current is too high, or if the electrodes are misplaced, get some of these collateral effects.”

“Finally, there has also been the possibility that there may be some therapeutic usage,” Dr. Lozano said. In patients with Parkinson’s disease and coexisting OCD, the OCD was improved with deep brain stimulation, leading to a trial currently being conducted in France, based on this chance observation.

He said deep brain stimulation for psychiatry is “an area of tremendous potential interest, but [it’s] also an area where caution is necessary.” Severe psychiatric illness affects about 6% of the US population, or one in 17 adults. Deep brain stimulation is used most frequently in patients with OCD. In addition to the subthalamic nucleus, other brain targets for stimulation include the internal capsule and the nucleus accumbens. In recent trials in which deep brain stimulation is used, 30% to 50% of patients with otherwise refractory OCD have shown a clinically relevant improvement. Similar target areas are also under investigation in patients with treatment-resistant depression.

According to Dr. Lozano, approximately 50 patients worldwide have received deep brain stimulation for Tourette’s syndrome, with about a 70% improvement. Based on imaging data that clearly showed specific brain abnormalities, two targets were selected for placement of electrodes in the brain: the thalamic interlaminar nuclei and the globus pallidus internus (the latter the same as in patients with Parkinson’s disease).

“My personal opinion about Tourette’s is that the number of patients that are candidates for surgery is very small, and that this will never really take off as mainstay therapy,” he said. “But for individual patients who are adults and very disabled, I think it’s something to consider.”

BRIDGING THE GAP

Dr. Lozano said one of his favorite quotes is: “The great divide between neurology and psychiatry has no anatomical basis.” He added, “These are very much the same circuits that are involved. In some cases, the disorders are treated by neurologists; and others, by psychiatrists, but fundamentally, the same processes are under way. Just as one can modulate the activity in motor circuits, it is also possible to modulate the activity in limbic circuits.

“The advantage of deep brain stimulation is that it is reversible: One can turn the device on and off, and one can adjust how much stimulation is being delivered,” he said. “There are many circuits in the brain that may be reachable and amenable to this. It is important to have a very strong scientific rationale to justify intervening in these circuits and intervening in these patients. Obviously, you need a multidisciplinary approach; but I think that this area of endeavor is one that shows great promise to be able to help our patients that are not, right now, being adequately treated by the means that we have available.”

Dr. Lozano said he understood he was the first neurosurgeon to have been invited to speak at an American Neuropsychiatric Association meeting. “One of the pleasures of working in this field is that there is now a rapprochement across several disciplines of neuroscientists, with neurology and psychiatry—and perhaps even neurosurgery—working together. The sum of what we do will be greater than its individual parts.”    

—Debra Hughes

Suggested Reading
Mink JW, Walkup J, Frey KA, et al. Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome. Mov Disord. 2006;21:1831-1838.

Return to table of contents