Intrinsic Functional Connectivity with the Subgenual Cingulate Predicts Clinical Efficacy of TMS Targets for Depression (P01.188)

Abstract

Objective: To elucidate the antidepressant mechanism of transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) and translate this information into improved TMS targeting and clinical efficacy. Background TMS to the left DLPFC is used clinically for the treatment of depression. However the antidepressant mechanism remains unclear and its therapeutic efficacy remains limited. One problem known to contribute to limited clinical efficacy is difficulty identifying the appropriate stimulation target. Recent data suggests that some left DLPFC targets are more effective than others; however the reasons for this heterogeneity and how to capitalize on this information remain unclear. Design/Methods: Intrinsic (resting state) functional connectivity MRI was used to determine if differences in functional connectivity could account for differences in clinical efficacy across various left DLPFC TMS sites. We then utilized this information to compute ideal stimulation coordinates using connectivity-based targeting. Results: The clinical efficacy of different DLPFC stimulation sites was related to the strength of their anticorrelation with the subgenual cingulate, both through paired comparisons and on a continuous basis. Optimal left DLPFC coordinates were identified based on subgenual connectivity to be targeted in future TMS clinical trials. Conclusions: This work lends insight into the antidepressant mechanism of TMS and the role of intrinsically anticorrelated networks in depression. Further, it suggests a targeting strategy to optimize focal brain stimulation that could have broad applicability across a number of diseases and stimulation techniques. Supported by: The Brain Genomics Superstruct Project, NIH Grant R25NS065743, National Institutes of Health and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758) and the Howard Hughes Medical Institute. Disclosure: Dr. Fox has nothing to disclose. Dr. Pascual-Leone has received personal compensation for activities with Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision.