Lateralization of forelimb motor evoked potentials by transcranial magnetic stimulation in rats

Abstract

Objectives: To approximate methods for human transcranial magnetic stimulation (TMS) in rats, we tested whether lateralized cortical stimulation resulting in selective activation of one forelimb contralateral to the site of stimulation could be achieved by TMS in the rat.

Methods: Motor evoked potentials (MEP) were recorded from the brachioradialis muscle bilaterally in adult male anesthetized rats (n=13). A figure-of-eight TMS coil was positioned lateral to midline. TMS intensity was increased stepwise from subthreshold intensities to maximal machine output in order to generate input-output curves and to determine the motor threshold (MT) for brachioradialis activation.

Results: In 100% of the animals, selective activation of the contralateral brachioradialis, in the absence of ipsilateral brachioradialis activation was achieved, and the ipsilateral brachioradialis was activated only at TMS intensities exceeding contralateral forelimb MT. With increasing TMS intensity, the amplitudes of both the ipsilateral and contralateral signals increased in proportion to TMS strength. However, the input-output curves for the contralateral and ipsilateral brachioradialis were significantly different (p<0.001) such that amplitude of the ipsilateral MEP was reliably lower than the contralateral signal.

Conclusions: We demonstrate that lateralized TMS leading to asymmetric brachioradialis activation is feasible with conventional TMS equipment in anesthetized rats.

Significance: These data show that TMS can be used to assess the unilateral excitability of the forelimb descending motor pathway in the rat, and suggest that rat TMS protocols analogous to human TMS may be applied in future translational research.

Figure 1. Rat and TMS Coil Setup

Anesthetized rats were placed into an electrically isolated metal rodent stereotactic frame. EMG was recorded from the brachioradialis muscle bilaterally as the figure-8 TMS coil was positioned with its center anterior and lateral to bregma. Active (white arrow), reference (black arrow) and ground (gray arrow) electrodes are indicated. The TMS coil midline is marked by a white triangle. Note, direction of electrical current (arrows on coil) is constant in with the coil positioned over either the left or the right hemisphere.

Figure 2. Representative Motor Evoked Potential (MEPs)

Lateralized ipsilateral (left) and contralateral (right) MEPs recorded from the brachioradialis in four rats are shown. Each tracing is an average of five MEPs at 100% MT. Latency to the start of the first positive deflection (*) was used to calculate timing of MEP onset. Note, the polyphasic appearance of the MEP signal required rectification to absolute values for statistical integration of voltages. Upward trace deflections correspond to negative voltage.

Figure 3. Lateralized Forelimb MEP Activation

Asymmetry of the MEP response to eccentric TMS coil position is demonstrated in a Kaplan-Meier curve which shows a greater proportion of rats with contralateral (solid line) than ipsilateral (dashed line) activation at suprapthreshold stimulator intensities

Figure 4. Ipsilateral-contralateral MEP Size Discrepancy

Input-output curves show consistently greater mean integrated (A) and maximal (B) voltage in the brachioradialis contralateral to the stimulated hemisphere at intensities > 70% MO. Error bars represent standard error of mean. (*) p<0.05; (**) p<0.01

Figure 4. Ipsilateral-contralateral MEP Size Discrepancy

Input-output curves show consistently greater mean integrated (A) and maximal (B) voltage in the brachioradialis contralateral to the stimulated hemisphere at intensities > 70% MO. Error bars represent standard error of mean. (*) p<0.05; (**) p<0.01

Figure 5. Contralateral and Ipsilateral MEPs

(A) Representative averaged sweeps from two rats show a predominantly contralateral MEP at 100% MT. (B) Bilateral MEPs are evident at stimulator of 112.5% MT (top) and 133.3 % MT (bottom). Five sweeps were averaged per tracing. Upward trace deflections correspond to negative voltage.