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

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.

[1]  L. Cohen,et al.  Transcranial magnetic stimulation in the rat , 2001, Experimental Brain Research.

[2]  P. Fitzgerald,et al.  A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition , 2006, Clinical Neurophysiology.

[3]  L. Cohen,et al.  Modulation of rodent cortical motor excitability by somatosensory input , 2002, Experimental Brain Research.

[4]  B N Cuffin,et al.  Developing a more focal magnetic stimulator. Part I: Some basic principles. , 1991, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[5]  Bryan Kolb,et al.  The variability of the interaural line vs the stability of bregma in rat stereotaxic surgery , 1977, Physiology & Behavior.

[6]  A. Barker,et al.  NON-INVASIVE MAGNETIC STIMULATION OF HUMAN MOTOR CORTEX , 1985, The Lancet.

[7]  M. Fujiki,et al.  Conduction pathways of motor evoked potentials following transcranial magnetic stimulation: A rodent study using a “Figure‐8” coil , 1998, Muscle & nerve.

[8]  B. Alstermark,et al.  Lack of monosynaptic corticomotoneuronal EPSPs in rats: disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons. , 2004, Journal of neurophysiology.

[9]  W. Paulus,et al.  Safety aspects of chronic low-frequency transcranial magnetic stimulation based on localized proton magnetic resonance spectroscopy and histology of the rat brain. , 2003, Journal of psychiatric research.

[10]  D. Cohen,et al.  Developing a more focal magnetic stimulator. Part II: Fabricating coils and measuring induced current distributions. , 1991, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[11]  Á. Pascual-Leone,et al.  Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen’s encephalitis , 2008, Epilepsy & Behavior.

[12]  Alvaro Pascual-Leone,et al.  Seizure suppression by EEG-guided repetitive transcranial magnetic stimulation in the rat , 2008, Clinical Neurophysiology.

[13]  R. Hopf,et al.  Serial recording of sensory, corticomotor, and brainstem-derived motor evoked potentials in the rat. , 2001, Somatosensory & motor research.

[14]  Ulf Ziemann,et al.  TMS and drugs , 2004, Clinical Neurophysiology.

[15]  Transcranial Magnetic Stimulation , 2009 .

[16]  M. Hallett Transcranial Magnetic Stimulation: A Primer , 2007, Neuron.

[17]  Klaus Funke,et al.  High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain , 2008, Experimental Brain Research.

[18]  Simone Rossi,et al.  Transcranial magnetic stimulation , 2007, Neurology.

[19]  J. Bufler,et al.  Pentobarbital Has Curare-Like Effects on Adult-Type Nicotinic Acetylcholine Receptor Channel Currents , 2000, Anesthesia and analgesia.

[20]  J. Aimonetti,et al.  Evaluation of transcranial magnetic stimulation for investigating transmission in descending motor tracts in the rat , 2007, The European journal of neuroscience.

[21]  M. Wiesendanger,et al.  Corticomotoneuronal connections in the rat: Evidence from double‐labeling of motoneurons and corticospinal axon arborizations , 1991, The Journal of comparative neurology.

[22]  M. Wiesendanger,et al.  Modulation of sustained electromyographic activity by single intracortical microstimuli: comparison of two forelimb motor cortical areas of the rat. , 1993, Somatosensory & motor research.

[23]  A T Barker,et al.  Magnetic stimulation of the human brain and peripheral nervous system: an introduction and the results of an initial clinical evaluation. , 1987, Neurosurgery.

[24]  Alvaro Pascual-Leone,et al.  Transcranial Magnetic Stimulation in Child Neurology: Current and Future Directions , 2008, Journal of child neurology.

[25]  Á. Pascual-Leone,et al.  Transcranial magnetic stimulation in neurology , 2003, The Lancet Neurology.