Ventral Capsule/Ventral Striatum Stimulation in Obsessive-Compulsive Disorder: Toward a Unified Connectomic Target for Deep Brain Stimulation?

Abstract

Introduction Obsessive‐compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. Deep brain stimulation (DBS) is a treatment option for severe therapy‐resistant OCD. Objective To provide a detailed clinical description and treatment outcome analysis in a cohort of eight refractory OCD patients receiving ventral capsule/ventral striatum (VC/VS) stimulation with the intention to validate discriminating fiber bundles previously associated with clinical response. Materials and Methods The primary outcome measure (the Yale‐Brown Obsessive Compulsive Scale [Y‐BOCS]) and secondary outcomes depressive symptoms, anxiety, and quality of life were retrospectively analyzed. DBS leads were warped into standard stereotactic space. A normative connectome was used to identify the neural network associated with clinical outcome. Results With a median stimulation duration of 26 months, patients exhibited a mean Y‐BOCS reduction of 10.5 resulting in a response rate of 63%. Modulation of a fiber bundle traversing the anterior limb of the internal capsule (ALIC) was associated with Y‐BOCS reduction. This fiber bundle connected the frontal regions to the subthalamic nucleus (STN) and was functionally identified as the hyperdirect pathway of the basal ganglia circuitry. Conclusion Our findings show that in VC/VS stimulation, the neural network associated with clinical outcome shows overlap with that of previously described for other targets namely the anterior limb of the internal capsula, the nucleus accumbens, or the STN, which supports the evolvement from the concept of an optimal gray matter target to conceiving the target as part of a symptom modulating network.

Connectomic Deep Brain Stimulation for Obsessive-Compulsive Disorder

“…An independent research group confirmed the predictive value of the pathway in 10 subjects with OCD and DBS of the ALIC/VS applying the same analysis procedure (32). A second group re-calculated an optimal tract using the same methodology on a novel sample eight patients and identified the same bundle in direct comparison to the published one (33). The significant association between clinical improvement and the extent of modulating this specific pathway was reproduced in both studies (32,33).…”

“…A second group re-calculated an optimal tract using the same methodology on a novel sample eight patients and identified the same bundle in direct comparison to the published one (33). The significant association between clinical improvement and the extent of modulating this specific pathway was reproduced in both studies (32,33).…”

“…Second, connectomic studies for DBS strongly depend on the validity of the modelled white matter pathways and how activation hereof is determined which is again subject to relevant limitations. In case of OCD, many studies relied on a similar whole-brain normative connectome and fiber filtering approach based on isotropic electric field models (1,28,(32)(33)(34). More complex biophysical field modeling methods have been developed that may lead to more detailed insights and superior results when predicting clinical effects, in the future (66)(67)(68).…”

“…While some of the aforementioned studies agreed on the critical role of the same fiber bundle published as a three-dimensional dataset (1,28,29,(32)(33)(34), others revealed seeming heterogeneity about which pathway would be critical to modulate for successful DBS in OCD. Namely, the study by J o u r n a l P r e -p r o o f Liebrand et al suggested that the MFB, connecting the PFC with the ventral tegmental area, would be associated with a beneficial response (26) whereas other studies highlighted streamlines within the ALIC as being critical for OCD-DBS (28,32,42).…”

“…In all of these trials, a monopolar high-frequency stimulation (> 80 Hz) was applied, the pulse width was mostly selected above 60 µs, although often considerably higher (up to 120-450 µs) for the ALIC/NAc/BNST area (62,65). For the previously discussed studies on connectomic DBS for OCD, no specific patient selection and similar stimulation parameters were chosen (1,30,32,33,62). Higher activation thresholds of fibers of passage (e.g.…”