Urvakhsh Meherwan Mehta1, Milind Vijay Thanki2, Jaya Padmanabhan3, Alvaro Pascual-Leone3, Matcheri S Keshavan4. 1. Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India. Electronic address: urvakhsh@nimhans.ac.in. 2. Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India. 3. Division of Cognitive Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 4. Department of Psychiatry, Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Harvard Medical School, Boston, MA, USA.
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.
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 schizophreniapatients 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:Schizophreniapatients 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.
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