Abstract
Although theta-burst stimulation (TBS) is known to differentially modify motor cortical excitability according to stimulus conditions in humans, whether similar effects can be seen in animals, in particular rats, remains to be defined. Given the importance of experimental rat models for humans, this study explored this stimulation paradigm in rats. Specifically, this study aimed to explore corticospinal excitability after TBS in anesthetized animals to confirm its comparability with human results. Both inhibition-facilitation configurations using paired electrical stimulation protocols and the effects of the TBS paradigm on motor-evoked potentials (MEPs) in rat descending motor pathways were assessed. Paired-stimulation MEPs showed inhibition [interstimulus interval (ISI): 3 ms] and facilitation (11 ms) patterns under medetomidine/midazolam/butorphanol (MMB) anesthesia. Furthermore, while ketamine and xylazine (K/X) anesthesia completely blocked facilitation at 11-ms ISI, inhibition at a 3-ms ISI was preserved. Continuous and intermittent TBS strongly facilitated MEPs depending on stimulus intensity, persisting for up to 25 min under both MMB and K/X anesthesia. These findings are similar to the intracortical inhibition and facilitation observed in the human motor cortex using paired-pulse magnetic stimulation, particularly the glutamate-mediated facilitation phase. However, different TBS facilitatory mechanisms occur in the rat motor cortex. These different TBS facilitatory mechanisms affect the comparability and interpretations of TBS between rat and human models.
Highlights
The non-invasive neuromodulation method can potentially be used as an adjuvant strategy in the rehabilitation of motor and cognitive deficits caused by neurological disorders (Müller-Dahlhaus and Vlachos, 2013; Rodger and Sherrard, 2015)
Theta-burst stimulation (TBS) of the motor cortex (3–5 pulses at 100 Hz repeated at 5 Hz), which was originally reported in animal studies in the hippocampus of cats and rats (Hess and Donoghue, 1996), has been successfully translated in the awake human motor cortex as either intermittent and facilitatory or continuous and inhibitory theta-burst stimulation (TBS) paradigms for motor-evoked potentials (MEPs) with repetitive transcranial magnetic stimulation
Direct motor cortical and epidural stimulation-induced MEPs were compared for accuracy verification
Summary
The non-invasive neuromodulation method can potentially be used as an adjuvant strategy in the rehabilitation of motor and cognitive deficits caused by neurological disorders (Müller-Dahlhaus and Vlachos, 2013; Rodger and Sherrard, 2015). Theta-burst stimulation (TBS) of the motor cortex (3–5 pulses at 100 Hz repeated at 5 Hz), which was originally reported in animal studies in the hippocampus of cats and rats (Hess and Donoghue, 1996), has been successfully translated in the awake human motor cortex as either intermittent and facilitatory or continuous and inhibitory TBS paradigms for motor-evoked potentials (MEPs) with repetitive transcranial magnetic stimulation (rTMS; Huang et al, 2005). Recent TMS-TBS protocols and MEP recording methods in animal models have been useful for translation purposes and for understanding the mechanisms underlying human results (Vahabzadeh-Hagh et al, 2011; Hsieh et al, 2012, 2015; Sykes et al, 2016). Electrical motor cortical stimulation would enable focal stimulation protocols with greater specificity and accuracy for basic MEP recording, intracortical inhibition-facilitation exploration, and TBS modulation in rat models
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