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

Abstract

Background: Transcranial magnetic stimulation can be combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) to evaluate the excitatory and inhibitory functions of the cerebral cortex in a standardized manner. It has been postulated that schizophrenia is a disorder of functional neural connectivity underpinned by a relative imbalance of excitation and inhibition. The aim of this review was to provide a comprehensive overview of TMS-EMG and TMS-EEG research in schizophrenia, focused on excitation or inhibition, connectivity, motor cortical plasticity and the effect of antipsychotic medications, symptom severity and illness duration on TMS-EMG and TMS-EEG indices. Methods: We searched PsycINFO, Embase and Medline, from database inception to April 2020, for studies that included TMS outcomes in patients with schizophrenia. We used the following combination of search terms: transcranial magnetic stimulation OR tms AND interneurons OR glutamic acid OR gamma aminobutyric acid OR neural inhibition OR pyramidal neurons OR excita* OR inhibit* OR GABA* OR glutam* OR E-I balance OR excitation-inhibition balance AND schizoaffective disorder* OR Schizophrenia OR schizophreni*. Results: TMS-EMG and TMS-EEG measurements revealed deficits in excitation or inhibition, functional connectivity and motor cortical plasticity in patients with schizophrenia. Increased duration of the cortical silent period (a TMS-EMG marker of γ-aminobutyric acid B receptor activity) with clozapine was a relatively consistent finding. Limitations: Most of the studies used patients with chronic schizophrenia and medicated patients, employed cross-sectional group comparisons and had small sample sizes. Conclusion: TMS-EMG and TMS-EEG offer an opportunity to develop a novel and improved understanding of the physiologic processes that underlie schizophrenia and to assess the therapeutic effect of antipsychotic medications. In the future, these techniques may also help predict disease progression and further our understanding of the excitatory/inhibitory balance and its implications for mechanisms that underlie treatment-resistant schizophrenia.

The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity

“…In line with most studies, we noted no change in RMT in schizophrenia. 49 Similar to Tang et al ., 76 we found reduced MEP amplitudes in both schizophrenia groups. Furthermore, our MEP results are numerically similar to studies that found no difference from HC.…”

“…SICI resembles another indirect in vivo probe of GABA A -related activity. 45 , 49 Higher cortical inhibition seems to be associated with better motor execution and coordination. 50-53 A substantial body of evidence suggests reduced SICI in schizophrenia across different stages of this disorder.…”

“… 48 The amplitude of motor evoked potential (MEP) informs on the excitability of corticospinal neurons and the influence of GABAergic and glutamatergic tone. 49 The short-interval intracortical inhibition (SICI) paradigm applies two stimuli over M1, where the first subthreshold stimulus triggers a reduced response to a subsequent stimulus. SICI resembles another indirect in vivo probe of GABA A -related activity.…”

“… 50-53 A substantial body of evidence suggests reduced SICI in schizophrenia across different stages of this disorder. 49 , 54 , 55 But the association of this inhibitory impairment with symptoms remains unclear.…”

Prolonged Intermittent Theta Burst Stimulation Targeting the Left Prefrontal Cortex and Cerebellum Does Not Affect Executive Functions in Healthy Individuals

“…Schizophrenia is a heterogeneous disorder varying in symptomatology, aberrant cortical connectivity, brain plasticity, complex comorbidities and medication uses which differentially affect TMS cognitive and neurophysiological effects 41 . To provide further insights into whether HF-rTMS targeting the LDLPFC or cerebellum vermis may be more promising for improving negative symptoms and cognition in schizophrenia, this study aimed to better understand the neurophysiological effects of rTMS to these two brain sites, by investigating effects on higher level neurocognitive function and electrophysiological measures, in healthy participants without confounding factors.…”