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

Abstract

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 31 st , 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 Δ) between patients and healthy subjects following TMS or tDCS. After examining heterogeneity, metaanalyses were performed using fixed effects models. Results-A total of 16 datasets comparing cortical plasticity (MEP Δ) between 189 schizophrenia patients and 187 healthy controls were included in the meta-analysis. Patients demonstrated diminished MEP Δ 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 LTP-and LTD-like motor cortical plasticity, which is not influenced by the various clinical and experimental protocol related *

Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia

“…Importantly, these results are not consistent with a more recent study using a different visual cortical plasticity paradigm in which a stimulus-specific (analogous to “input specificity” in LTP) VEP plasticity effect was demonstrated and found to be intact in schizophrenia patients ( 44 ). However, they are broadly consistent with other studies showing schizophrenia patients to have LTP-like auditory plasticity deficits using a high frequency auditory stimulation paradigm ( 48 ) and motor plasticity deficits using transcranial magnetic stimulation [see ( 78 )] and transcranial direct current stimulation [see ( 79 )] plasticity induction paradigms. This observed LTP-like plasticity deficit in schizophrenia may be a consequence NMDAR hypofunction, which in turn may arise from schizophrenia risk genes ( 13 , 80 , 81 ).…”

Network-level mechanisms underlying effects of transcranial direct current stimulation (tDCS) on visuomotor learning

“…In addition to its specific findings regarding tDCS modulation of motor learning in the SRTT in healthy individuals, the present study may also have direct implications for use of network-targeted tDCS for treatment of motor manifestations of neuropsychiatric disorders. Thus, it has become increasingly appreciated that “whole brain” diseases such as schizophrenia have a prominent motor component including impairments in TMS-induced motor plasticity ( Mehta et al, 2019 ) that may significantly contribute to poor treatment outcome ( Green et al, 2004 ; Morrens et al, 2014 ). To this end, a motor domain has recently been added to the Research Domain Criteria (RDoC) matrix of the NIMH, facilitating future research ( Bernard and Mittal, 2015 ).…”

A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia

“…However, a recent meta-analysis reported that illness duration might not influence motor cortical plasticity in schizophrenia, and that altered plasticity may predate the manifestation of clinical symptoms. 181 Furthermore, Hasan and colleagues 45 speculated that patients with chronic schizophrenia might have disturbed GABAergic neurotransmission because tDCS enhanced SICI only in those with recent-onset schizophrenia. Still, no significant difference in SICI was found among those with recent-onset schizophrenia, multi-episode schizophrenia or healthy controls before tDCS administration in that study, and SICI was not correlated with the number of psychotic episodes or duration of psychosis in patients with schizophrenia.…”