Efficacy and time course of paired associative stimulation in cortical plasticity: Implications for neuropsychiatry

Objective: Paired associative stimulation (PAS) has been used to study normal and abnormal cortical plasticity. However, a normative review of PAS effects has not been provided so far. To this end, the magnitude and time course of PAS protocols was systematically evaluated here. Methods: A literature search in PubMed using the search term paired associative stimulation was conducted. Main inclusion criteria were that experiments were conducted in primary motor cortex of healthy volunteers without motor training before intervention and motor evoked potentials as primary outcome measure. This search yielded in total 104 experiments, which were analyzed to examine the potentiating (PAS(LTP)) and depressing effects of PAS (PAS(LTD)) on cortical excitability levels in healthy volunteers. Results: PAS(LTP) induces reliable and stable potentiating effects (maximum +/- standard error 38.5 +/- 3.3%) on cortical excitability levels up to 90 min. PAS(LTP) was most effective when applied at frequencies of 0.05 and 0.2 Hz. Analyses of the PAS(LTD) studies demonstrated reliable and stable depression of cortical excitability levels up to 120 min (maximum +/- standard error -23.0 +/- 1.9%) Conclusions: PAS significantly modulates cortical excitability. The potentiating effects of PAS(LTP) are stronger than the depressing effects for PAS(LTD). Significance: Present findings offer normative insights into the magnitude and time course of PAS(LTP) and PASLTD-induced changes in cortical excitability levels. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.