In Vitro Assessment Reveals Parameters-Dependent Modulation on Excitability and Functional Connectivity of Cerebellar Slice by Repetitive Transcranial Magnetic Stimulation

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.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

“…In vitro , TMS can be utilized to assess the cellular (Vlachos et al, 2012 ; Tang et al, 2016 ) and sub-cellular impacts of TMS (Murphy et al, 2016 ). For instance, sub-cellular recordings using optical fiber imaging revealed that single-pulse TMS caused GABA B mediated inhibition of dendritic activity—a finding with direct relevance to the scalp EEG signal that reflects largely dendritic depolarization (Murphy et al, 2016 ).…”

“…For instance, sub-cellular recordings using optical fiber imaging revealed that single-pulse TMS caused GABA B mediated inhibition of dendritic activity—a finding with direct relevance to the scalp EEG signal that reflects largely dendritic depolarization (Murphy et al, 2016 ). In vitro studies in isolated brain slices examined the effect of rTMS in hippocampal (Vlachos et al, 2012 ) or cerebellar slice cultures to confirm that rTMS results in an LTP-like durable increase in glutamatergic synaptic strength (Vlachos et al, 2012 ), or leads to frequency-dependent modulation of functional connectivity (Tang et al, 2016 ).…”

Frequency-Dependent Effects of Cerebellar Repetitive Transcranial Magnetic Stimulation on Visuomotor Accuracy

“…In contrast, intermittent TBS (iTBS), a form of excitatory cerebellar TMS, was found to improve visuomotor learning ability in a visuomotor adaptation task (Koch et al, 2019). Furthermore, physiological evidence has demonstrated that cerebellar rTMS has frequency-dependent effects in the cerebellar cortex (Tang et al, 2016), including altered firing rates of cerebellar neurons (Tang et al, 2016) and synapse plasticity (Koch, 2010).…”

“…In particular, high-frequency (HF) rTMS increases while low-frequency (LF) rTMS decreases cortical excitability in the target region (Ziemann et al, 1996;Hallett, 2000;Maeda et al, 2000;Pascual-Leone et al, 2000;Walsh and Cowey, 2000). Regarding the rTMS frequency-dependent effects on the cerebellum, an in vitro study found that LF rTMS induced short-term inhibition, whereas HF rTMS induced the excitation effect with electrophysiological evidences (Tang et al, 2016). Langguth et al (2008) demonstrated that motor cortex excitability decreased after LF cerebellar rTMS with a frequency-dependent effect, but behavioral data were lacking (Langguth et al, 2008).…”

Baseline Cerebro-Cerebellar Functional Connectivity in Afferent and Efferent Pathways Reveal Dissociable Improvements in Visuomotor Learning

“…We calculated improvements in performance at the minimum distance from the target point as indices of accuracy and the trial-to-trial variability of distance from the target as indices of stability (Lien et al, 2022). Visuomotor learning performance can be modulated by repetitive cerebellar transcranial magnetic stimulation (rTMS) (Koch, 2010;Lee et al, 2014;Tang et al, 2016;Rastogi et al, 2017). Therefore, we used different frequencies (1 Hz and 10 Hz) of cerebellar rTMS to influence visuomotor coordination abilities in the pursuit rotor task.…”