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Towards refinement of neuromodulation targets in ObsessiveCompulsive Disorder: Insights from Causal Network Mapping
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Orientador(es)
Resumo(s)
Neuromodulation modalities such as Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS) have emerged as valuable alternatives for patients with obsessive-compulsive disorder (OCD) who are resistant to first-line therapies. While outcomes at the currently approved targets are promising given the complexity of this population, there remains room for optimization. In pursuit of stronger therapeutic effects, several non-approved targets have been explored. However, metaanalyses consistently report high variability in outcomes both between and within targets and protocols. This variability suggests that existing approaches may primarily engage circuits peripheral or nonspecific to OCD pathophysiology, limiting their capacity to deliver robust and consistent clinical benefit. This underscores the need for refined, circuit-informed strategies to optimize treatment. This dissertation addresses this gap with retrospective collection of clinical and neuroimaging data from patients who underwent TMS across three international centers and from patients treated with DBS at another center. Electric field modeling was performed using SIMNIBS for TMS and Lead-DBS for DBS. To enable this, a custom pipeline was developed to convert neuronavigation data into a SIMNIBScompatible reference space and to reconstruct coil positioning from stimulation parameters. Thresholded E-fields were used to define regions of interest and conduct normative weighted functional connectivity analyses. Voxel-wise correlations between connectivity and clinical outcomes revealed networks where modulation was associated with OCD symptom change – the TMS and DBS OCD improvement networks. Thresholding of the maps using observer-dependent criteria revealed peak regions previously implicated in OCD pathophysiology in the literature, with overlap between both networks. The TMS OCD Improvement Network showed significant spatial correlation with a lesional OCD network, while control analyses against lesional depression and mania networks confirmed disorderspecificity. Most notably, overlapping regions of thresholded TMS and lesional networks highlighted refined candidate targets in the medial orbitofrontal cortex and ventral basal ganglia.
Descrição
Tese de Mestrado, Engenharia Biomédica e Biofísica, 2025, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
obsessive-compulsive disorder transcranial magnetic stimulation deep brain stimulation electric field normative functional connectivity