Abstract
Repetitive transcranial magnetic stimulation (rTMS) is an increasingly common technique used to selectively modify neural excitability and plasticity. There is still controversy concerning the cortical response to rTMS of different frequencies. In this study, a novel in vitro paradigm utilizing the Multi-Electrodes Array (MEA) system and acute cerebellar slicing is described. In a controllable environment that comprises perfusion, incubation, recording and stimulation modules, the spontaneous single-unit spiking activity in response to rTMS of different frequencies and powers was directly measured and analyzed. Investigation using this in vitro paradigm revealed frequency-dependent modulation upon the excitability and functional connectivity of cerebellar slices. The 1-Hz rTMS sessions induced short-term inhibition or lagged inhibition, whereas 20-Hz sessions induced excitation. The level of modulation is influenced by the value of power. However the long-term response fluctuated without persistent direction. The choice of evaluation method may also interfere with the interpretation of modulation direction. Furthermore, both short-term and long-term functional connectivity was strengthened by 1-Hz rTMS and weakened by 20-Hz rTMS.
Highlights
Both multi-electrodes array (MEA) and neuroimaging techniques provide the spatiotemporal view of neural responses to Repetitive transcranial magnetic stimulation (rTMS), but unlike the latter, MEA measure the neural activity by direct electrophysiological recording to the neural firing
Previous studies have utilized computation modeling[25,26,27]. These simulation-based studies highlighted the importance of brain anatomy[28], geometry and positioning of the coil[29,30], which contributed to distribution of the electrical field
The results provide a precise measure of excitability based on the direct recording of the firing rate and information regarding functional connectivity consequences of rTMS that are not provided in traditional studies
Summary
The multi-electrodes array (MEA) system has been adapted to neural electrophysiological studies[11] It is capable of performing long-term, direct and noninvasive measurement of the extracellular electrical activity at the single-unit level. Apart from the complexity of the frequency effect itself, it has been suggested that many external factors may contributed to determine the level and direction of rTMS modulation, including coil geometry, positioning, stimulus duration, intensity, the number of stimuli, and cortical state[21,22] Among these factors, the rTMS-induced electrical field is especially important. The simulation together with measurement provided a map of the TMS-induced electrical field inside cerebellar slices, based on which the frequency-dependent modulation was evaluated. This MEA-based in vitro system has proved to be viable for evaluation of rTMS effects on cerebellar slices
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