Introduction: We conceptualize DBS of the ventral capsule/ventral striatum (VC/VS) region as facilitating “approach” behavior. An appropriate amount of stimulation can counteract the highly avoidant state of severe OCD and explain the therapeutic effect of DBS for this indication. Over-stimulation can drive overly exuberant approach behavior marked by disinhibition and recklessness.
Methods: Two patients with treatment-resistant OCD were implanted with recording-enabled DBS systems and provided neural recordings from the VC/VS target. We obtained clinical scales assessing severity of OCD, depression, and mania at pre- and post-DBS intervals up to 8 months.
Results: Patient 1 met responder criteria 12 days after DBS in terms of OCD (70% reduction) and depression (100% reduction) severity. Mania scores elevated moderately after DBS activation, indicating sustained disinhibited behavior characterized by abrupt occupation and relationship changes. Patient 2 met responder criteria 28 days after DBS in terms of OCD (51% reduction) and depression (81% reduction) severity. Mania scores elevated significantly from baseline, and behavior was characterized by substance use, sleep disruption, and gambling. Neural recordings showed a circadian pattern change coinciding with OCD improvement, aligning with our prior findings (Provenza et al. Nature Medicine 2024) linking symptom relief to disruption of pathologically periodic/predictable neural activity in the VS (linear autoregressive model; P1: p = 1.42e-12, P2: p = 0.020).
Conclusion : The unusually rapid reduction in OCD/depression symptoms (weeks vs. months) coincided with clinically significant disinhibited behavior. These findings support our model conceptualization of the pro-approach effect of VC/VS DBS and underscore the importance of carefully titrating the pace of stimulation delivery to balance the concurrent objectives of hastening clinical improvement while minimizing deleterious side effects.
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