Enhancing Cognitive Restructuring with Concurrent Repetitive Transcranial Magnetic Stimulation: A Transdiagnostic Randomized Controlled Trial

Introduction Emotional dysregulation constitutes a serious public health problem in need of novel transdiagnostic treatments. Objective To this aim, we developed and tested a one-time intervention that integrates behavioral skills training with concurrent repetitive transcranial magnetic stimulation (rTMS). Methods Forty-six adults who met criteria for at least one DSM-5 disorder and self-reported low use of cognitive restructuring (CR) were enrolled in a randomized, double-blind, sham-controlled trial that used a between-subjects design. Participants were taught CR and underwent active rTMS applied at 10 Hz over the right (n= 17) or left (n= 14) dorsolateral prefrontal cortex (dlPFC) or sham rTMS (n= 15) while practicing reframing and emotional distancing in response to autobiographical stressors. Results Those who received active left or active right as opposed to sham rTMS exhibited enhanced regulation ( d s = 0.21 - 0.62) as measured by psychophysiological indices during the intervention (higher high-frequency heart rate variability, lower regulation duration). Those who received active rTMS over the left DLPFC also self-reported reduced distress througout the intervention ( d = 0.30), higher likelihood to use CR, and lower daily distress during the week following the intervention. The procedures were acceptable and feasible with few side effects. Conclusions These findings show that engaging frontal circuits simultaneously with cognitive skills training and rTMS may be clinically feasible, well-tolerated and may show promise for the treatment of transdiagnostic emotional dysregulation. Larger follow up studies are needed to confirm the efficacy of this novel therapeutic approach. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02573246 ### Funding Statement This research and the completion of the manuscript were supported by a Brain and Behavior Young Investigator Award, a Duke internal award, and KL2 award granted to the first author and by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number 5KL2TR001115. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Duke University Health System Institutional Review Board Reviewed and approved the presented protocol All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes No external datasets or supplemental materials are available at this time. Data sets and protocol materials can be obtained by e-mailing the first author (andrada.neacsiu{at}duke.edu)