• Timothy P Morris, Paula Davila-Pérez, Ali Jannati, Arianna Menardi, Alvaro Pascual-Leone, and Peter J Fried.
• Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
• Neuroscience. 2019 Oct 15; 418: 157-165.

AbstractTo assess motor cortex neurophysiology, including the mechanisms of neuroplasticity, transcranial magnetic stimulation (TMS) is typically applied to the motor "hotspot"- the optimal site for inducing a twitch in a given target muscle. It is known that the effects of suprathreshold repetitive TMS (rTMS) spread along functional connections beyond the specific cortical stimulation target, and yet, it is unknown whether the aftereffects of subthreshold intermittent theta-burst stimulation (iTBS), an ultra-high frequency patterned rTMS protocol, extend beyond the targeted muscle. We investigated whether and to what extent iTBS induces changes in the cortical output to other intrinsic hand muscles with adjacent cortical representation to the target. Sixteen healthy adults underwent neuronavigated TMS-iTBS targeting the first dorsal interosseus (FDI) hotspot. Proportion of motor evoked potentials (MEPs) at the resting motor threshold (RMT), baseline MEP amplitude, and iTBS-induced changes in MEP amplitude were compared between FDI, abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. MEP amplitudes recorded from the three muscles at RMT and suprathreshold intensities indicated the chosen hotspots were relatively selective for FDI. Nevertheless, iTBS induced significant facilitation of MEPs recorded from both FDI and APB, but not ADM. Surprisingly, the MEP modulation was greater in APB, even when controlling for the baseline MEP amplitude. These results indicate that iTBS modulation of cortico-spinal excitability extends beyond the representation of the targeted muscle. Results have implications both for how iTBS may be used in clinical treatment and for the safety guidelines for the application of iTBS.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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