Transcranial magnetic stimulation and PAS-induced cortical neuroplasticity in the awake rhesus monkey.
OBJECTIVE
Externally induced neuroplasticity may be of therapeutic value in several neuro-psychiatric disorders. To facilitate research on mechanisms and to make possible the design of prospective, advanced stimulation protocols without exposing human subjects to risk, we have developed a primate model which allows us to assess changes of motor cortical excitability using transcranial magnetic stimulation (TMS).


METHODS
TMS hand muscle representation and cortical excitability were determined in two awake trained rhesus monkeys. Neuroplastic changes of cortical excitability were established by 13min of paired associative stimulation (PAS) with interstimulus intervals of either 15 or 5ms.


RESULTS
The representational areas of FDI and APB muscles (3.02-4.96cm(2)) were located between the spur of the arcuate and the superior precentral sulcus, indicating the potential to carry out spatially selective cortical stimulation. PAS with an interstimulus interval of 15ms strongly increased cortical excitability for up to two hours, while 5ms interval had no effect.


CONCLUSIONS
This first systematic TMS and PAS primate study demonstrates that the trained rhesus monkeys represent an exceptional animal model that allows cortical TMS mapping as well as non-invasive assessment and induction of cortical neuroplasticity.


CONCLUSIONS
This animal model offers additional advantageous options not possible with humans, namely an alternative to invasive, morphological or molecular analyses, making it highly suitable for preclinical development of advanced neuroplasticity paradigms without exposing human subjects to risk.
Amaya
Franco
F
Department of Clinical Neurophysiology, Georg-August University, 37075 Göttingen, Germany.
Paulus
Walter
W
Treue
Stefan
S
Liebetanz
David
D
D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor / Q000502:physiology*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000379:methods; D008475:Median Nerve / Q000502:physiology; D009044:Motor Cortex / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D012146:Rest / Q000502:physiology; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation; D014851:Wakefulness / Q000502:physiology*