Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy

Abstract

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

Figure 1

Distribution of oscillatory activity of subthalamic neurons recorded in obsessive–compulsive disorder (OCD) and Parkinson's disease (PD) patients. (a) Relative proportion of the 138 and 173 subthalamic nucleus (STN) neurons showing oscillatory activity in OCD and PD patients. Asterisks indicate significant differences (P<0.05) between neurons of OCD and PD patients. (b) Subthalamic oscillatory activity as a function of subthalamic subdivisions in OCD and PD patients. Top histogram: relative proportion of neurons recorded in the sensorimotor (SM), associative (AS) and limbic (LI) subdivisions and showing none, one or more than one period of significant oscillatory activity. Bottom histogram: relative proportion of neurons recorded in the SM, AS and LI subdivisions and showing significant oscillatory activity in the θ, α, β-low, β-high and γ band frequencies.

Figure 2

Subthalamic neuronal activity as a function of subthalamic subdivisions in obsessive–compulsive disorder (OCD) and Parkinson's disease (PD) patients. (a) Localisation by means of the three-dimensional (3D) digitised distortable basal ganglia atlas of all the neurons recorded in OCD and PD patients. The motor part is represented in green, the associative part in pink and the limbic part in yellow in a 3D posterior view of both sides. Each sphere represents an individual neuron (orange for subthalamic nucleus (STN)-OCD neurons and blue for STN-PD neurons). (b–d) Mean firing rate, burst index and intraburst frequency plotted against the three subthalamic subdivisions (sensorimotor, SM; associative, AS; limbic, LI) for STN neurons recorded in OCD (orange bars) and PD (blue bars) patients. Asterisks indicate significant differences (P<0.05) between a given subdivision in OCD patients and the same subdivision in PD patients.

Figure 3

Improvement in obsessions and compulsions with subthalamic nucleus stimulation as a function of subthalamic neuronal activity in obsessive–compulsive disorder patients. The graphs represent the relationship between the improvement in the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) global (green circles), obsession (blue crosses) and compulsion (red squares) subscores and the mean (a) discharge frequency, (b) burst frequency, (c) intraburst frequency and (d) interburst interval.