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Meta-Analysis
. 2019 May:207:37-47.
doi: 10.1016/j.schres.2018.10.027. Epub 2018 Nov 6.

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

Urvakhsh Meherwan Mehta  1 , Milind Vijay Thanki  2 , Jaya Padmanabhan  3 , Alvaro Pascual-Leone  3 , Matcheri S Keshavan  4
Affiliations
Meta-Analysis

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

Urvakhsh Meherwan Mehta et al. Schizophr Res. 2019 May.

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 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 Δ) 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 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 confounders. These consistent findings should encourage the use of perturbation-based biomarkers to characterize illness trajectories and treatment response.

Keywords: Biological marker; Cortical plasticity; Motor cortex; Psychosis; Transcranial Magnetic Stimulation.

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Figures

Figure-1
Figure-1. Illustration of TMS-EEG or TMS-EMG cortical plasticity experiments
Figure-2
Figure-2. Flowchart representing the study selection process
Figure-3
Figure-3. Cortical plasticity (MEP Δ) meta-analysis forest plot for all datasets
Forest plot for cortical plasticity (MEP Δ) meta-analyses between schizophrenia patients and healthy subjects; MEP Δ = change in motor evoked potential amplitudes following a neuromodulatory perturbation protocol. See supplementary table-S1 for more details
Figure-4
Figure-4. Cortical plasticity (MEP Δ) meta-analysis forest plots for LTD-like and LTP-like cortical plasticity
4A and 4B are forest plots for LTD-like and LTP-like cortical plasticity (MEP Δ) meta-analyses respectively; MEP Δ = change in motor evoked potential amplitudes following a neuromodulatory perturbation protocol. See supplementary table-S1 for more details
Figure-5
Figure-5. Bubble plots of effect sizes representing cortical plasticity (MEP Δ) impairments in schizophrenia patients compared to healthy subjects
X-axes (5A: generic division & 5B: specific division) represent the different neuromodulatory perturbation protocols used in the selected studies and Y-axes represent the effect sizes (size of the circle is weighted for sample size
See this image and copyright information in PMC

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