Electrophysiological dynamics of inhibitory control in obsessive-compulsive disorder during nucleus accumbens stimulation

Resumen

The core symptoms of obsessive-compulsive disorder (OCD) have been attributed to certain features of impulsivity and compulsivity, which are most likely caused by corticostriatal circuitry disturbances. For medication-refractory OCD patients, deep brain stimulation (DBS) of the nucleus accumbens (NAc) has emerged as the preferred target, with promising clinical results. However, the processes behind the efficacy of NAc-DBS are not completely understood. In this study, we aimed to assess the impact of NAc-DBS on electric brain activity as measured by electroencephalography (EEG) sensors, so we could better characterize the critical interactions of frontal-basal ganglia networks and the underlying neural mechanisms by which NAc stimulation modulates brain activity in OCD patients during both resting-state periods and during inhibitory control task performance. Here, 10 refractory OCD patients treated with DBS were evaluated by two single blind experiments to address the dynamic modulations of large-scale cortico-subcortical network activity involved in inhibitory control after NAc stimulation and their possible relationship with the underlying cortical thickness of key frontal regions. Results showed no significant modulation after NAc stimulation in the examined frequency bands during resting EEG. Nevertheless, during equiprobable AX-CPT task performance, patients committed fewer errors and exhibited increased intraindividual reaction time variability when comparing DBS On/Off states, indicative of improved proactive and reactive control, context processing and goal maintenance abilities. Event-related potentials (ERP) showed increased amplitudes for P3, but not N2 components, displaying also increased cortical activation for Go and Nogo conditions, mainly over the right inferior frontal gyrus and medial frontal gyrus, respectively. Moreover, increased cortical activation in these areas was associated with a higher cortical thickness within the prefrontal cortex. These results highlight the critical role of NAc-DBS for preferentially modulating the neuronal activity underlying sustained speed responses and inhibitory control in OCD patients by reorganizing brain functions to the right prefrontal regions, which may depend, likewise, on the underlying cortical thickness. Furthermore, the dynamic and transient modulation caused by NAc-DBS appears to be more perceptible during the performance of cognitive task as opposed to resting states. These results may offer insights for the restoration of normal activity between different brain regions and within damaged functional networks. Our findings provide updated structural and functional evidence that supports critical dopaminergic-mediated frontal-striatal network interactions in OCD.