Toward Personalized Deep Brain Stimulation for Obsessive-Compulsive Disorder

Deep brain stimulation (DBS) is an effective treatment for patients with severe obsessive-compulsive disorder (OCD) who are refractory to therapy and medication. Unlike most conventional psychiatric treatments, DBS is a circuit-selective intervention uniquely influencing cognitive-behavioral symptoms in a personalized way. Implanted DBS leads contain multiple electrode contacts that can be separately activated for selective modulation of connected brain pathways. For OCD, the most often used target for lead placement is the anterior limb of the internal capsule (ALIC). Stimulation in this target allows for modulation of parallel white matter pathways connecting corticostriatal circuits (CSCs) involved in emotional, cognitive, or behavioral aspects of decision making. Personalized ALIC DBS would require measuring outcomes reflecting these circuit-selective decision-making functions that are not typically captured in clinical scales. In the current issue of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Schüller et al. ( ) investigated how DBS in the ALIC and nucleus accumbens influences impulsive decision making and related brain pathways in 15 patients with OCD. Patients performed the Cambridge Gambling Task during active and inactive DBS on 2 consecutive days. Active DBS increased impulsive decision making, as indicated by reduced risk adjustment, and increased delay aversion, which did not correlate with the clinical OCD outcomes of DBS. Previous studies have also reported increased decision impulsivity in patients treated with DBS independent of clinical benefits, or problematic impulsive behaviors as side effects of ALIC DBS ( , ). This could suggest that ALIC DBS may help some but not all patients with OCD by promoting impulsive decision making. Schüller et al. also performed a structural (normative) connectivity analysis of impulsive decision making. Impulsivity was related to stimulation of a pathway between the medial and lateral prefrontal cortex and a specific set of neural structures, i.e., the subthalamic nucleus (STN), thalamus, and globus pallidus pars externa and interna. These structures are part of limbic and associative CSC pathways involved in inhibitory control and flexibility. Inhibitory high-frequency DBS of the suppressive indirect CSC may reduce inhibitory control and promote behavioral flexibility, which can be beneficial for individuals engaged in rigid compulsive behaviors but can promote problematic impulsivity in others. In line with this, in patients with Parkinson’s disease, ventral (anteromedial) STN DBS, which is also a treatment for OCD and within the same indirect CSC, enhances behavioral flexibility at the cost of impaired self-control when patients are faced with competing choices ( ).