Improving Obsessive-compulsive Disorder Treatments: from Lesions to Neuromodulation Targets

While in most cases of obsessive-compulsive disorder (OCD) a cause cannot be identified, this syndrome may develop as a consequence of focal brain lesions. Neuropsychiatric disorders secondary to brain insults are open windows to understand their underlying neurobiology. Different neuroimaging analysis methods, including pooled lesion topography and lesion network mapping, can be used to study lesional neuropsychiatric syndromes, including OCD. If successful, these strategies can also reveal new neuromodulation treatment targets, including for transcranial magnetic stimulation (TMS). Indeed, TMS targets to treat depression evolved from evidence extracted from lesional studies that were then refined and validated. For OCD treatment with TMS, already approved by the FDA and European Commission, targets were defined using a distinct approach, not involving causal brain lesions, which may contribute to lower than desirable remission rates. Lesional OCD is characterized by specific dysfunctional brain circuits. These circuits may be effectively targeted by TMS, which may optimize treatment of OCD. To address these hypotheses, we will test the therapeutic benefits of optimizing brain targets for the currently used TMS treatment of OCD, using information from the lesional-OCD brain network namely refining the target in the medial orbitofrontal cortex, bilaterally. Specifically, we will conduct a randomized clinical interventional study, using TMS to treat patients with OCD with inadequate response to other treatments, comparing, within the approved protocol for OCD treatment, the most frequently used stimulation site with a new target, adjusted according to the connectivity of lesions associated with the occurrence of OCD. If successful, our results may have immediate clinical implications in OCD treatment, as it will contribute to refine current therapeutic TMS strategies for OCD and defining new clinical research strategies in this domain.