A new measure of cortical inhibition by mechanomyography and paired-pulse transcranial magnetic stimulation in unanesthetized rats

Abstract

A new measure of cortical inhibition by mechanomyography and paired-pulse transcranial magnetic stimulation in unanesthetized rats. J Neurophysiol 107: 966 -972, 2012. First published October 19, 2011 doi:10.1152/jn.00690.2011.-Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive tool for measuring cortical inhibition in humans, particularly in patients with disorders of cortical inhibition such as epilepsy. However, ppTMS protocols in rodent disease models, where mechanistic insight into the ppTMS physiology and into disease processes may be obtained, have been limited due to the requirement for anesthesia and needle electromyography. To eliminate the confounding factor of anesthesia and to approximate human ppTMS protocols in awake rats, we adapted the mechanomyogram (MMG) method to investigate the ppTMS inhibitory phenomenon in awake rats and then applied differential pharmacology to test the hypothesis that long-interval cortical inhibition is mediated by the GABA A receptor. Bilateral hindlimbevoked MMGs were elicited in awake rats by long-interval ppTMS protocols with 50-, 100-, and 200-ms interstimulus intervals. Acute changes in ppTMS-MMG were measured before and after intraperitoneal injections of saline, the GABA A agonist pentobarbital (PB), and GABA A antagonist pentylenetetrazole (PTZ). An evoked MMG was obtained in 100% of animals by single-pulse stimulation, and ppTMS resulted in predictable inhibition of the test-evoked MMG. With increasing TMS intensity, MMG amplitudes increased in proportion to machine output to produce reliable input-output curves. Simultaneous recordings of electromyography and MMG showed a predictable latency discrepancy between the motor-evoked potential and the evoked MMG (7.55 Ϯ 0.08 and 9.16 Ϯ 0.14 ms, respectively). With pharmacological testing, time course observations showed that ppTMS-MMG inhibition was acutely reduced following PTZ (P Ͻ 0.05), acutely enhanced after PB (P Ͻ 0.01) injection, and then recovered to pretreatment baseline after 1 h. Our data support the application of the ppTMS-MMG technique for measuring the cortical excitability in awake rats and provide the evidence that GABA A receptor contributes to long-interval paired-pulse cortical inhibition. Thus ppTMS-MMG appears a well-tolerated biomarker for measuring GABA A -mediated cortical inhibition in rats.long-interval intracortical inhibition; mechanomyogram; GABA TRANSCRANIAL MAGNETIC STIMULATION (TMS) is a well-tolerated technique for measuring regional cortical excitability that is gaining acceptance as a means to examine cortical physiology in healthy human subjects and in patients with neurological disorders such as epilepsy, stroke, and mild concussion (Manganotti et al. 2001(Manganotti et al. , 2008Tremblay et al. 2011;Valzania et al. 1999). In TMS, the cortex is activated by a powerful fluctuating extracranial magnetic field, which induces small intracranial electrical currents (reviewed in Kobayashi and PascualLeone 2003). In humans, TMS can be applied to the moto...

Novel Use of Theta Burst Cortical Electrical Stimulation for Modulating Motor Plasticity in Rats

“…To record cortical excitability in rats, settings similar to those described in earlier reports using TMS were applied here to measure cortical excitability in anesthetized rats [15,16,18]. The MEP morphology and latency are consistent with published cortically derived MEPs in rats, suggesting that the recorded MEP signal is from the target area of the motor cortex [19].…”

Novel insights into skeletal muscle function by mechanomyography: from the laboratory to the field

“…All the six studies catalogued within this area, used muscles from a mammalian model (four studies used rat's muscle and two cat's muscles). Five of them analysed the gastrocnemius muscle [8,[64][65][66][67], while the other investigated the tibialis anterior muscle [68].…”

“…Hsieh et al [68] used MMG signal to investigate the paired-pulse transcranial magnetic stimulation inhibitory phenomenon in awaked rats, and then applied differential pharmacology to test the hypothesis that long-interval cortical inhibition is mediated by the GABA A receptor. Their results demonstrated predictable latency discrepancy between the motor-evoked potential and the evoked MMG.…”

The Epilepsy Foundation's 4th Biennial Epilepsy Pipeline Update Conference

“…Uniquely among brain stimulation methods, TMS has robust diagnostic and therapeutic capacities that are relevant to the study and management of epilepsy. Transcranial magnetic stimulation protocols can be divided into three categories: repetitive TMS (rTMS), which modulates brain excitability; single-pulse TMS (spTMS), which evokes a motor response or other observable change in cortical function; and paired-pulse TMS (ppTMS), which is a means to assess the excitation:inhibition ratio [41,42]. In common spTMS and ppTMS protocols, a hand-held electromagnetic coil is positioned next to the scalp and generates a brief, approximately 2-Tesla, magnetic field, which induces an electrical current in the nearby cortex [41].…”