Jürgen Germann1, Alexandre Boutet1,2, Gavin J B Elias1, Flavia Venetucci Gouveia3, Aaron Loh1, Peter Giacobbe4, Venkat Bhat5, Walter Kucharczyk1,2, Andres M Lozano1. 1. Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada. 2. Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada. 3. Neuroscience and Mental Health, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada. 4. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 5. Centre for Mental Health and Krembil Research Centre, University Health Network, Toronto, Ontario, Canada.
Abstract
BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating disease with a lifetime prevalence of 2-3%. Neuromodulatory treatments have been successfully used in severe cases. Deep brain stimulation (DBS) targeting the inferior thalamic peduncle (ITP) has been shown to successfully alleviate symptoms in OCD patients; however, the brain circuits implicated remain unclear. Here, we investigate the efficacious neural substrates following ITP-DBS for OCD. METHODS: High-quality normative structural and functional connectomics and voxel-wise probabilistic mapping techniques were applied to assess the neural substrates of OCD symptom alleviation in a cohort of 5 ITP-DBS patients. RESULTS: The region of most efficacious stimulation was located in the regions of the ITP and bed nucleus of the stria terminalis. Both functional and structural connectomics analyses demonstrated that successful symptom alleviation involved a brain network encompassing the bilateral amygdala and prefrontal regions. LIMITATIONS: The main limitation is the small size of the ITP-DBS cohort. While the findings are highly consistent and significant, these should be validated in larger studies. CONCLUSIONS: These results identify a tripartite brain network - composed of the bilateral amygdala and prefrontal regions 24 and 46 - whose engagement is associated with greater symptom improvement. They also provide information for optimizing targeting and identifying network components critically involved in ITP-DBS treatment response. Amygdala engagement in particular seems to be a key component for clinical benefits and could constitute a biomarker for treatment optimization.
BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating disease with a lifetime prevalence of 2-3%. Neuromodulatory treatments have been successfully used in severe cases. Deep brain stimulation (DBS) targeting the inferior thalamic peduncle (ITP) has been shown to successfully alleviate symptoms in OCD patients; however, the brain circuits implicated remain unclear. Here, we investigate the efficacious neural substrates following ITP-DBS for OCD. METHODS: High-quality normative structural and functional connectomics and voxel-wise probabilistic mapping techniques were applied to assess the neural substrates of OCD symptom alleviation in a cohort of 5 ITP-DBS patients. RESULTS: The region of most efficacious stimulation was located in the regions of the ITP and bed nucleus of the stria terminalis. Both functional and structural connectomics analyses demonstrated that successful symptom alleviation involved a brain network encompassing the bilateral amygdala and prefrontal regions. LIMITATIONS: The main limitation is the small size of the ITP-DBS cohort. While the findings are highly consistent and significant, these should be validated in larger studies. CONCLUSIONS: These results identify a tripartite brain network - composed of the bilateral amygdala and prefrontal regions 24 and 46 - whose engagement is associated with greater symptom improvement. They also provide information for optimizing targeting and identifying network components critically involved in ITP-DBS treatment response. Amygdala engagement in particular seems to be a key component for clinical benefits and could constitute a biomarker for treatment optimization.