Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder.

CONTEXT: Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that affects 2% of the general population. Even when the best available treatments are applied, approximately 10% of patients remain severely afflicted and run a long-term deteriorating course of OCD. OBJECTIVE: To determine whether bilateral deep brain stimulation of the nucleus accumbens is an effective and safe treatment for treatment-refractory OCD. DESIGN: The study consisted of an open 8-month treatment phase, followed by a double-blind crossover phase with randomly assigned 2-week periods of active or sham stimulation, ending with an open 12-month maintenance phase. SETTING: Academic research. Patients Sixteen patients (age range, 18-65 years) with OCD according to DSM-IV criteria meeting stringent criteria for refractoriness to treatment were included in the study. INTERVENTIONS: Treatment with bilateral deep brain stimulation of the nucleus accumbens. MAIN OUTCOME MEASURES: Primary efficacy was assessed by score change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Responders were defined by a score decrease of at least 35% on the Y-BOCS. RESULTS: In the open phase, the mean (SD) Y-BOCS score decreased by 46%, from 33.7 (3.6) at baseline to 18.0 (11.4) after 8 months (P < .001). Nine of 16 patients were responders, with a mean (SD) Y-BOCS score decrease of 23.7 (7.0), or 72%. In the double-blind, sham-controlled phase (n = 14), the mean (SD) Y-BOCS score difference between active and sham stimulation was 8.3 (2.3), or 25% (P = .004). Depression and anxiety decreased significantly. Except for mild forgetfulness and word-finding problems, no permanent adverse events were reported. CONCLUSION: Bilateral deep brain stimulation of the nucleus accumbens may be an effective and safe treatment for treatment-refractory OCD. CLINICAL TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN23255677.

Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans.

We test the hypothesis that interaction between the human basal ganglia and cerebral cortex involves activity in multiple functional circuits characterized by their frequency of oscillation, phase characteristics, dopamine dependency and topography. To this end we took recordings from macroelectrodes (MEs) inserted into the subthalamic nucleus (STN) in eight awake patients following functional neurosurgery for Parkinson's disease. An EEG was also recorded, as were the signals from MEs in the globus pallidus interna (GPi) in two of the cases. Coherence between EEG and ME potentials was apparent in three major frequency bands, 2-10 Hz, 10-30 Hz and 70-85 Hz. These rhythmic activities differed in their cortical topography, although coherence was always strongest over the midline. Coherence between EEG and ME potentials in the 70-85 Hz band was only recorded in patients treated with levodopa. Cortical activity phase led that in the basal ganglia in those oscillatory activities with frequencies <30 Hz. In contrast, STN and GPi phase led cortex in the 70-85 Hz band. The temporal differences in the way in which cortical activity led or lagged behind that in STN/GPi were similar, around 20 ms, regardless of the overall direction of information flow and frequency band. We conclude that the basal ganglia may receive multiple cortical inputs at frequencies <30 Hz and, in the presence of dopaminergic activity, produce a high frequency drive back to the cerebral cortex, in particular the supplementary motor area (SMA).