Accelerated neuromodulation in treatment-resistant depression: preclinic model characterization and treatment evaluation by multimodal MRI

Motivation: There is a need to improve treatment options for treatment-resistant depression (TRD). Goal(s): We compared a validated TRD rat model (i.e. Wistar-Kyoto rats, an endogenous MDD model, to which a chronic mild stress protocol was applied) with non-depressed Wistar rats, and we explored the effects of accelerated repetitive transcranial magnetic stimulation (arTMS) in the TRD model, by comparing active vs. sham intervention. Approach: We use a translational approach including behavioral and multimodal MRI analyses. Results: Brain metabolism and structure alterations (in shape, volume and connections) were detected in the TRD model, which were partially normalized following arTMS intervention, thus demonstrating its efficacy. Impact: Our results show that increasing daily stimulation frequency allows to shorten treatment duration without compromising rTMS efficacy. The application of accelerated neuromodulation in clinical settings would improve patient compliance and cost-effectiveness.