Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study

Abstract Background Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. Objective To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Methods Longitudinal intralimbic and limbic–prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. Results An early significant intralimbic FC decrease significantly predicted a later increase in limbic–prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Conclusions Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic–prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response.