Repetitive transcranial magnetic stimulation for post-stroke depression: a randomised trial with neurophysiological insight

Objective: Despite high incidence of depression after stroke, few trials have investigated the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). Here, we aimed to evaluate clinical benefit of delivering a higher dose of rTMS compared to previous stroke trials. Secondary aims were to document adverse effects and investigate the role of functional connectivity as a potential mechanism of clinical response to rTMS treatment. Methods: Eleven chronic stroke survivors were recruited to a double-blind, Sham-controlled, randomised trial to investigate 10 sessions of high-frequency rTMS for depression. Clinical assessments were obtained at baseline, after treatment and a 1-month follow-up. Adverse events were documented at completion of the treatment. Resting electroencephalography recordings were performed at baseline and after treatment to estimate functional connectivity. Results: There were no differences in baseline characteristics between groups (all p ≥ 0.42). Beck Depression Inventory scores decreased for the Active rTMS group from baseline to 1-month follow-up (p = 0.04), but did not change for the Sham group at post-treatment or follow-up (p ≥ 0.17). Stronger theta frequency functional connectivity between the left frontal cortex and right parietal cortex was associated with lower baseline depression (r = − 0.71, p = 0.05). This network strength increased following Active rTMS, with change in connectivity associated with improvement in BDI scores (r = 0.98, p = 0.001). Adverse events were transient and minor and were not statistically different between groups (p ≥ 0.21). Conclusions: Active rTMS significantly improved depression and was well tolerated. The mechanistic role of theta frequency functional connectivity appears worthy of further investigation.Brenton Hordacre, Kristina Comacchio, Lindy Williams, Susan Hillie