Transcranial magnetic stimulation and PAS-induced cortical neuroplasticity in the awake rhesus monkey

Abstract

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 13 min of paired associative stimulation (PAS) with interstimulus intervals of either 15 or 5 ms. Results The representational areas of FDI and APB muscles (3.02–4.96 cm 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 15 ms strongly increased cortical excitability for up to two hours, while 5 ms 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. Significance 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.