title: Efficacy and time course of paired associative stimulation in cortical plasticity: Implications for neuropsychiatry.
abstract: 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 (PASLTP) and depressing effects of PAS (PASLTD) on cortical excitability levels in healthy volunteers.
  
  
  RESULTS
  PASLTP induces reliable and stable potentiating effects (maximum ± standard error 38.5 ± 3.3%) on cortical excitability levels up to 90 min. PASLTP was most effective when applied at frequencies of 0.05 and 0.2 Hz. Analyses of the PASLTD 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 PASLTP are stronger than the depressing effects for PASLTD.
  
  
  CONCLUSIONS
  Present findings offer normative insights into the magnitude and time course of PASLTP and PASLTD-induced changes in cortical excitability levels.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, The Netherlands. Electronic address: m.wischnewski@donders.ru.nl.
authors.forename: Miles
authors.initials: M
authors.lastname: Wischnewski
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, The Netherlands.
authors.forename: Dennis J L G
authors.initials: DJLG
authors.lastname: Schutter
mesh_terms: D001245:Association Learning / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000502:physiology*; D006801:Humans; D001523:Mental Disorders / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D009044:Motor Cortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D058027:Neuropsychiatry; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: Cortical excitability; Cortical plasticity; Long-term depression; Long-term potentiation; Motor cortex; Paired associative stimulation