Motor cortical plasticity in schizophrenia: A meta-analysis of Transcranial Magnetic Stimulation - Electromyography studies

Background: Several lines of investigations converge upon aberrant synaptic plasticity as a potential pathophysiological characteristic of schizophrenia. In vivo experiments using neuromodulatory perturbation techniques like Transcranial Magnetic and Direct Current Stimulation (TMS & tDCS) have been increasingly used to measure 'motor cortical plasticity' in schizophrenia. A systematic quantification of cortical plasticity and its moderators in schizophrenia is however lacking. Method: The PubMed/MEDLINE database was searched for studies up to December 31st, 2017 that examined case-control experiments comparing neuromodulation following single-session of TMS or tDCS. The primary outcome was the standardized mean difference for differential changes in motor evoked potential (MEP) amplitudes measured with single-pulse TMS (MEP Delta) between patients and healthy subjects following TMS or tDCS. After examining heterogeneity, meta-analyses were performed using fixed effects models. Results: A total of 16 datasets comparing cortical plasticity (MEP Delta) between 189 schizophrenia patients and 187 healthy controls were included in the meta-analysis. Patients demonstrated diminished MEP Delta with effect sizes (Cohen's d) ranging from 0.66 (LTP-like plasticity) to 0.68 (LTD-like plasticity). Heterosynaptic plasticity studies demonstrated a greater effect size (0.79) compared to homosynaptic plasticity studies (0.62), though not significant (P = 0.43). Clinical, perturbation protocol- and measurement-related factors, and study quality did not significantly moderate the aberrant plasticity demonstrated in schizophrenia. Conclusions: Schizophrenia patients demonstrate diminished LIP- and LTD-like motor cortical plasticity, which is not influenced by the various clinical and experimental protocol related confounders. These consistent findings should encourage the use of perturbation-based biomarkers to characterize illness trajectories and treatment response. (C) 2018 Elsevier B.V. All rights reserved.