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

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Repetitive transcranial magnetic stimulation for post‑stroke depression: a randomised trial with neurophysiological insight Brenton Hordacre1   · Kristina Comacchio1 · Lindy Williams1 · Susan Hillier1 Received: 18 October 2020 / Revised: 5 November 2020 / Accepted: 8 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract 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. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001303134) on September 23, 2019. Keywords  Depression · Stroke · Repetitive transcranial magnetic stimulation · Connectivity · Electroencephalography Abbreviations BDI Beck depression inventory—II DLPFC Dorsolateral prefrontal cortex dwPLI Debiased weighted phase lag index FDI First dorsal interosseous MEP Motor evoked potential Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0041​5-020-10315​-6) contains supplementary material, which is available to authorized users. * Brenton Hordacre [email protected] 1



Innovation, IMPlementation and Clinical Translation (IIMPACT) in Health, Allied Health and Human Performance, University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia 50