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.
Objective: The efficacy of deep brain stimulation in disorders of consciousness remains inconclusive. We investigated bilateral 30‐Hz low‐frequency stimulation designed to overdrive neuronal activity by dual pallido‐thalamic targeting, using the Coma Recovery Scale Revised (CRS‐R) to assess conscious behavior.Methods: We conducted a prospective, single center, observational 11‐month pilot study comprising four phases: baseline (2 months); surgery and titration (1 month); blind, random, crossover, 1.5‐month ON and OFF periods; and unblinded, 5‐month stimulation ON. Five adult patients were included: one unresponsive‐wakefulness‐syndrome male (traumatic brain injury); and four patients in a minimally conscious state, one male (traumatic brain injury) and three females (two hemorrhagic strokes and one traumatic brain injury). Primary outcome measures focused on CRS‐R scores. Secondary outcome measures focused notably on baseline brain metabolism and variation in activity (stimulation ON – baseline) using normalized fluorodeoxyglucose positron emission tomography maps. Statistical analysis used random‐effect models.Results: The two male patients (one minimally conscious and one unresponsive wakefulness syndrome) showed improved mean CRS‐R scores (stimulation ON vs. baseline), in auditory, visual and oromotor/verbal subscores, and visual subscores respectively. The metabolism of the medial cortices (low at baseline in all five patients) increased specifically in the two responders.Interpretation: Our findings show there were robust but limited individual clinical benefits, mainly in visual and auditory processes. Overall modifications seem linked to the modulation of thalamo‐cortico‐basal and tegmental loops activating default mode network cortices. Specifically, in the two responders there was an increase in medial cortex activity related to internal awareness.
Deep brain stimulation (DBS) therapy requires extensive patient-specific planning prior to implantation to achieve optimal clinical outcomes. Collective analysis of patient's brain images is promising in order to provide more systematic planning assistance. In this paper the design of a normalization pipeline using a group specific multi-modality iterative template creation process is presented. The focus was to compare the performance of a selection of freely available registration tools and select the best combination. The workflow was applied on 19 DBS patients with T1 and WAIR modality images available. Non-linear registrations were computed with ANTS, FNIRT and DRAMMS, using several settings from the literature. Registration accuracy was measured using single-expert labels of thalamic and subthalamic structures and their agreement across the group. The best performance was provided by ANTS using the High Variance settings published elsewhere. Neither FNIRT nor DRAMMS reached the level of performance of ANTS. The resulting normalized definition of anatomical structures were used to propose an atlas of the diencephalon region defining 58 structures using data from 19 patients.