Abstract

Abstract Transcranial magnetic stimulation (TMS) can non-invasively induce excitatory or inhibitory neural activity depending on the stimulation parameters. However, the neurophysiological basis for both kinds of modulation remains elusive. Here, with a controlled dosage over the 30-s interval, we elicited excitatory and inhibitory modulations over the human primary motor cortex (M1) with TMS bursts of high (10-Hz and 30-Hz; HF) and low frequency (0.5-Hz; LF), respectively, and took functional magnetic resonance images (fMRI) and electromyography (EMG) recordings simultaneously. We used a customized 8-channel head coil array to integrate with an MRI-compatible TMS coil connected to the stimulator on a 3T MRI scanner. Images were prescribed to cover the left M1. Each TMS-fMRI run consisted of five 30-second “TMS on” and 30-second “TMS off” blocks. One of five types of TMS stimuli was administered in the “TMS-on” block: 0.5-Hz, 10-Hz-3-pulses-per-burst (ppb), 10-Hz-5-ppb, 30-Hz-3-ppb, and 30-Hz-5-ppb. In each TR (2s), images were acquired between 0 and 1 s after the start of each volume acquisition, and TMS pulses were delivered during the MRI silent period. EMG responses were calculated the peak-to-peak amplitudes from the time interval between 20 and 40 ms after the TMS onset. Image pre-processing and General Linear Model were performed using SPM12. Excitatory and inhibitory modulations were evidenced by changes in EMG responses to the HF and LF stimulation, respectively. Significantly increased fMRI signal at M1 was only detected under excitatory HF TMS but not during inhibitory LF TMS. The supplementary motor area (SMA) had significant fMRI signal changes after both TMS. The topology of the activated M1 and SMA matched the activated sensorimotor network during voluntary movement. These findings demonstrated the asymmetric hemodynamic responses to excitatory HF and inhibitory LF TMS modulations with region-dependent relationships between the local fMRI signal changes and TMS dosage over different time scales. Keywords: Transcranial magnetic stimulation, Functional magnetic resonance imaging, Primary motor cortex, Frequency

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