Test-retest reliability of short-interval intracortical inhibition and intracortical facilitation in patients with schizophrenia

Abstract

Impaired short-interval intracortical inhibition (SICI) elicited by paired-pulse TMS (ppTMS) has emerged as one of the most consistent TMS findings in patients with schizophrenia. Reduction of SICI has been reproducibly found, suggesting that SICI may be a new biomarker indexing the inhibitory dysfunction in schizophrenia. This study evaluated whether SICI has the test-retest reliability suitable for clinical trial and research applications. SICIs, intracortical facilitation (ICF), and other ppTMS effects were obtained using inter-stimulus intervals (ISIs) from 1 to 500 ms, on 2 occasions about 3-4 weeks apart in patients with schizophrenia and healthy individuals. Acceptable test-retest reliabilities were found for SICI (at 1 and 3 ms ISIs) in both patients and controls (all intraclass correlation coefficients r > 0.6). However, test-retest reliability in longer ISIs and in ICF were modest or poor. To our knowledge, this is the first study demonstrated the acceptable reliability of SICI measure in patients with schizophrenia. The data support SICI as a reliable biomarker for schizophrenia.

Mapping local and long-distance resting connectivity markers of TMS-related inhibition reduction in schizophrenia

“…Trials were randomized and delivered in one session, with intertrial intervals jittered between 4 and 10 s. Participants were evaluated in two sessions about 4 weeks apart. High reproducibility of the paired-pulse effects between the two sessions was was observed and previously reported ( Du and Hong, 2018 ). Therefore, we merged the data from the two sessions to obtain robust and reliable representation of SICI (i.e., 24 trials for test stimulation and 24 trials for SICI).…”

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

“…Interpretation of the few other studies that demonstrated increased and decreased RMT may reflect disease heterogeneity or the persisting effects of medication. 97 Amplitude of motor evoked potentials Amplitudes of MEPs did not differ between patients with chronic schizophrenia (medicated and unmedicated) and healthy controls, regardless of whether the hand area of the primary motor cortex was stimulated with a suprathreshold intensity, 87 at 120% RMT 79,82 or with the lowest stimulus intensity required to produce maximum MEPs. 94 Similarly, MEPs did not differ between patients (most of whom were medicated) and healthy controls when the motor cortex was stimulated with an intensity intended to elicit an average MEP of 1 mV amplitude (SI-1mV), in either intensity 76,89,97,99 or amplitude.…”

“…In 15 of the 19, no significant differences in RMT were reported between patients and healthy controls. 54,60,[78][79][80][81][82][83][84][85][86][87][88][89][90] This lack of difference in RMT was observed in patients with chronic schizophrenia but also extended to medication-naive or minimally treated (< 1 month) patients with first-episode psychosis. 91 Lower RMT values (indicating increased corticospinal excitability) were reported in only 1 study of medicated patients with schizophrenia, but also in patients with major depressive disorder and manic disorder.…”

“…Resting motor threshold Fifteen studies reported no significant differences between medicated patients with chronic schizophrenia and healthy controls; 54,60,[78][79][80][81][82][83][84][85][86][87][88][89][90] 1 study 91 reported no significant difference between medication-naive or minimally treated (< 1 month) patients with first-episode psychosis and healthy controls; 1 study reported lower RMT in medicated patients; 92 2 studies reported higher RMT in medicated patients with chronic schizophrenia; 93,94 1 study showed higher RMT in medicated patients 45 Patients would show deficits in GABA-mediated cortical inhibition as measured by CSP and pairedpulse inhibition paradigms (e.g., SICI and LICI). Intracortical facilitation may not be significantly different between patients and healthy controls Active motor threshold Two studies reported no significant differences between patients with chronic schizophrenia (mostly medicated) and healthy controls 84,86 or healthy siblings 86 Amplitude of motor evoked potentials Four studies found no significant differences between medicated and unmedicated patients with chronic schizophrenia and healthy controls; 81,82,87,94 2 studies reported unaltered MEP sizes in medicated patients with first-episode schizophrenia 58 and medicated patients; 89 1 study found smaller MEP sizes in medicated chronic patients; 54 1 study found increased MEP sizes in medicated patients with chronic schizophrenia; 88 1 study found no significant differences between patients with recent-onset and multi-episode schizophrenia, people at risk and healthy controls; 1 study found smaller MEP sizes in people at risk compared to patients with first-episode schizophrenia and healthy controls 45 Duration of cortical silent period Four studies found no significant differences between medicated patients with chronic schi...…”

“…Eight studies reported reduced SICI in medicated patients with chronic schizophrenia, 45,54,60,81,82,89,93 patients with recent-onset schizophrenia 60 and medicated patients with first-episode schizophrenia; 58 1 study reported unchanged SICI in patients with chronic schizophrenia and medication resistance; 95 1 study reported unchanged SICI in medicated patients with chronic schizophrenia at interstimulus intervals of 1, 2, 3 and 4 ms but when data for the 4 interstimulus intervals were pooled, patients showed reduced SICI; 84 1 study reported reduced SICI in people at risk; 56 1 study found unchanged SICI in people at risk. 54 Intracortical facilitation Seven studies reported no significant differences between medicated patients with chronic schizophrenia and healthy controls; 45,54,60,82,84,93,95 1 study found no significant difference between people at risk, medicated patients with chronic schizophrenia and healthy controls; 54 1 study reported mixed results: reduced intracortical facilitation in medicated patients with chronic schizophrenia compared to healthy controls in 1 experimental session, but no difference between the groups in another session that was 4~8 days apart 89 Long-interval intracortical inhibition…”