Mechanisms of DBS: from informational lesions to circuit modulation and implications in OCD

Julia Shea ^* Chaim Feigen Emad Eskandar Nathaniel J Killian

• Albert Einstein College of Medicine, New York City, United States

In 2010, treatment-resistant OCD was FDA-approved as an indication for deep brain stimulation (DBS) under a Humanitarian Device Exemption (HDE). This review examines the mechanisms by which DBS may produce its effects, with specific attention to how it may interact with the pathophysiology of OCD, a psychiatric condition thought to be caused by overactive corticostriatal-thalamo-cortical (CSTC) circuits. We first review initial theories of excitation and inhibition. We then transition to discussion of the "informational lesion" hypothesis, which suggests that DBS may prevent the transmission of usual neural activity through the stimulated region. Specifically, high frequency stimulation may disrupt pathological network patterns by masking or antidromically blocking synaptic inputs. Another hypothesis explaining a disruption of network activity is that by driving action potentials antidromically, DBS may activate upstream inhibitory interneurons, imposing rhythmic activity on local regions based on DBS stimulation parameters. Recent animal studies support theories of disruption of pathological network activity, showing that high-frequency DBS can prevent neurons from responding to intrinsic oscillations, and thereby perhaps relieve OCD symptoms. This review also discusses the variable effects of DBS, noting immediate improvements in mood and anxiety, with a gradual reduction in OCD symptoms over time. These differential findings suggest that DBS may produce its effects through both immediate neuromodulation and long-term synaptic remodeling. In summary, this review synthesizes current mechanistic understanding of DBS with a focus on OCD, highlighting areas of discrepancies between studies and opportunities for future research.