Electrical orbitofrontal cortex stimulation boosts mood in epilepsy patients Direct intracranial electrical stimulation of the orbitofrontal cortex produced acute mood improvement in a small study of epilepsy patients with moderate-to-severe depression, researchers reported. The stimulation, applied with implanted electrodes in patients being evaluated for epilepsy surgery, appeared to modulate mood-related circuitry and may point to a new target with therapeutic potential that may extend beyond patients with epilepsy, according to Edward Chang, MD, of the University of California San Francisco and co-authors, writing online in Current Biology. "Depression is a common co-morbidity among those with epilepsy," said co-author Heather Dawes, PhD, also of University of California San Francisco. "The reasons for this are not well understood, and it remains to be seen whether there are any real differences in the forms of depression that occur in patients with epilepsy and those without," she told MedPage Today. "If the biological underpinnings of depression in patients with and without epilepsy are the same or similar, then it may be that certain interventions may be effective for treating depression in both groups of patients," she noted. Hypotheses about brain chemical imbalances in mood disorders have sparked interest in selective neural network modulation with deep brain stimulation (DBS) in recent years. Well-studied targets for DBS in treatment-resistant depression include the subgenual cingulate cortex and subcortical structures, but results have been inconclusive. A significant challenge is that mood disorders are heterogeneous and can involve dysfunction in cognitive, affective, and reward systems. "The orbitofrontal cortex has been called one of the least understood regions in the brain, but it is richly connected to various brain structures linked to mood, depression, and decision making, making it very well positioned to coordinate activity between emotion and cognition," Chang said in a statement. In this study, the researchers studied a group of 25 epilepsy patients who had intracranial electroencephalography electrodes implanted in their brains as part of standard preparation for neurosurgery. These electrodes typically help surgeons identify and remove brain tissue responsible for seizures while avoiding nearby tissue involved in other functions. The team used a mild electrical current to disrupt brain activity systematically in candidate regions including the orbitofrontal cortex, amygdala, cingulate cortex, insula, and hippocampus, asking patients to report the effect on their mood on a set of standardized scales. The team assessed mood both in the moment with a composite measure of self-report and speech analysis and prior to surgery through Beck Depression Inventory scores. Most stimulation locations produced no effect on mood, but a current applied to the lateral orbitofrontal cortex for 3 minutes produced significant improvements in some patients and triggered wide-spread patterns of brain activity that resembled what had occurred naturally during positive moods in the days before brain stimulation. Patients did not experience any symptoms of mania as a result of the stimulation. Lateral orbitofrontal cortex stimulation improved the mood only in patients with moderate-to-severe depression symptoms, but had no effect on patients with milder symptoms. The researchers did not measure the duration of the effect, which may have varied from patient to patient, Dawes said. "But, the onset of the mood effect was fairly quick, within a few minutes," she noted. And, it's unknown whether this approach can help depression patients actually recover from depression, she added. Patients in the study had a mix of treatment histories for depression, and whether any individuals had treatment-resistant depression was not a question the researchers examined. "But, we are very interested in knowing whether the lateral orbitofrontal cortex for stimulation approach might help patients who do not have epilepsy, but who do have treatment-resistant depression," Dawes said. "These patients suffer significant disability, and at the same time, lack any good options for treating their disease." Among the study limitations, Chang and colleagues noted, were the small sample size, and although electrode coverage was extensive in their patients, basal ganglia structures known to be important for mood are usually not implanted with electrodes in epilepsy surgery. The patients all had medically refractory epilepsy and may not be representative of other patients with mood disorders, and the findings need to be replicated in other cohorts, the researchers said. Source
