TMS site connectivity to an anxiosomatic network predicts improvements in emotional conflict regulation

Abstract Background: Deficits in emotional regulation are associated with various psychiatric disorders, particularly generalized anxiety disorder. Here, we determine whether TMS site connectivity to two previously published networks specific to dysphoric and anxious/somatic symptoms of depression (derived from TMS site connectivity) predicts changes in emotional conflict regulation as measured by a transdiagnostic behavioral task. Connectivity to these networks may help define future TMS targets to affect emotional conflict regulation. Methods: 57 participants received clinical TMS for MDD across two separate institutions with standard scalp-based targeting. All subjects received a baseline MRI scan, the incidental stimulation site was localized using structural neuronavigation, and the Emotional Conflict Resolution task was completed before and after treatment. In this validated task (Etkin et al, 2006), participants are scored on their ability to identify emotional expression on happy and angry faces. Using a normative connectome dataset (n=1000), we estimated whole-brain connectivity of each TMS site to our independently generated dysphoric and anxiosomatic circuits. We hypothesized a priori that connectivity to the anxiosomatic network would predict post-treatment ECR score independently of connectivity to the dysphoric circuit, controlling for baseline ECR and data collection site. Results: Connectivity to both maps predicted changes in conflict regulation (Anxiosomatic: r=-0.3162, p=0.017; Dysphoric: r=0.3019, p=0.022). However, a combined regression model showed that only connectivity to the Anxiosomatic circuit independently predicted ECR (partial r=-0.2726, p=0.040). Increased stimulation site connectivity to the circuit was associated with improvement in emotional conflict regulation scores. Connectivities to three control circuits (parkinsonism, akinetic mutism, and prosopagnosia) were not predictive. Conclusions: For the first time, we demonstrated that the Anxiosomatic circuit is a discrete entity that predicts clinical outcomes independently of the Dysphoric circuit. This may elucidate future stimulation targets for altering or improving emotional conflict regulation. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: TMS, Depression, Emotional Conflict Regulation, Anxiosomatic