Test-retest reliability of short-interval intracortical inhibition and intracortical facilitation in patients with schizophrenia.
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ABSTRACT:
SUBMITTER: Du X
PROVIDER: S-EPMC6131061 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Test-retest reliability of short-interval intracortical inhibition and intracortical facilitation in patients with schizophrenia.
Du Xiaoming X Hong L Elliot LE
Psychiatry research 20180619
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 ppT ...[more]
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Project description:GABAergic and glutamatergic dysfunction in the dorsolateral prefrontal cortex (DLPFC) are thought to be the core pathophysiological mechanisms of schizophrenia. Recently, we have established a method to index these functions from the DLPFC using the paired transcranial magnetic stimulation (TMS) paradigms of short interval intracortical inhibition (SICI) and facilitation (ICF) combined with electroencephalography (EEG). In this study, we aimed to evaluate neurophysiological indicators related to GABAA and glutamate receptor-mediated functions respectively from the DLPFC in patients with schizophrenia using these paradigms, compared to healthy controls. Given that these activities contribute to cognitive functions, the relationship between the TMS-evoked potential (TEP) modulations by SICI/ICF and cognitive/clinical measures were explored. Compared to controls, patients showed reduced inhibition in P60 (t22?=?-4.961, p?<?0.0001) by SICI and reduced facilitation in P60 (t22?=?5.174, p?<?0.0001) and N100 (t22?=?3.273, p?=?0.003) by ICF. In patients, the modulation of P60 by SICI was correlated with the longest span of the Letter-Number Span Test (r?=?-0.775, p?=?0.003), while the modulation of N100 by ICF was correlated with the total score of the Positive and Negative. Syndrome Scale (r?=?0.817, p?=?0.002). These findings may represent the pathophysiology, which may be associated with prefrontal GABAA and glutamatergic dysfunctions, in the expression of symptoms of schizophrenia.
| S-EPMC5719013 | biostudies-literature
Project description:The reliability of magnetoencephalography (MEG) resting-state functional connectivity in schizophrenia (SZ) is unknown as previous research has focused on healthy controls (HC). Here, we examined reliability in 26 participants (13-SZ, 13-HC). Eyes opened and eyes closed resting-state data were collected on 4 separate occasions during 2 visits, 1 week apart. For source modeling, we used minimum norm software to apply dynamic statistical parametric mapping. Source analyses compared the following functional connectivity metrics from each data run: coherence (coh), imaginary coherence (imcoh), pairwise phase consistency (ppc), phase-locking value (plv), phase lag index (pli), weighted phase lag index (wpli), and weighted phase lag index debiased (wpli2). Intraclass correlation coefficients (ICCs) were calculated for whole brain, network, and network pair averages. For reliability, ICCs above 0.75 = excellent, above 0.60 = good, above 0.40 = fair, and below 0.40 = poor reliability. We found the reliability of these metrics varied greatly depending on frequency band, network, network pair, and participant group examined. Broadband (1-58 Hz) whole brain averages in both HC and SZ showed excellent reliability for wpli2, and good to fair reliability for ppc, plv, and coh. Broadband network averages showed excellent to good reliability across 1 hour and 1 week for coh, imcoh, ppc, plv, wpli within default mode, cognitive control, and visual networks in HC, while the same metrics had excellent to fair reliability in SZ. Regional network pair averages showed good to fair reliability for coh, ppc, plv within default mode, cognitive control and visual network pairs in HC and SZ. In general, HC had higher reliability compared to SZ, and the default mode, cognitive control, and visual networks had higher reliability compared to somatosensory and auditory networks. Similar reliability levels occurred for both eyes opened and eyes closed resting-states for most metrics. The functional connectivity metrics of coh, ppc, and plv performed best across 1 hour and 1 week in HC and SZ. We also found that SZ had reduced coh, plv, and ppc in the dmn average and pair values indicating dysconnectivity in SZ. These findings encourage collecting both eyes opened and eyes closed resting-state MEG, while demonstrating that clinical populations may differ in reliability.
| S-EPMC7772354 | biostudies-literature
Project description:BackgroundPulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction.ObjectivesTo investigate whether SICI evaluated with AP and PA conditioning stimuli (CSPA and CSAP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TSPA).MethodsUsing two superimposed TMS coils, CSPA and CSAP were applied at interstimulus intervals (ISI) of 1-5 ms before a TSPA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICICSPA3 and SICICSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICICSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICICSPA3 and SICICSAP3.ResultsCSAP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CSAP and CSPA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICICSPA3 or SICICSAP3 with other forms of inhibition led to quite different results: SICICSPA3 interacted in complex ways with CBI, SAI and SICICSPA2, whereas the effect of SICICSAP3 appeared to be quite independent of them. Although SICICSPA and SICICSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICICSAP was disinhibited much earlier following the imperative signal than SICICSPA.ConclusionsSICICSPA appears to activate a different inhibitory pathway to that activated by SICICSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.
| S-EPMC8460995 | biostudies-literature
Project description:BackgroundShort-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear.ObjectiveTo compare T-SICI and its reliability with conventional A-SICI measurements.MethodsIn twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50-80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator.ResultsAcross the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7-0.3x, R2 = 0.99), but there was considerable interindividual variability. At CS 60-80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81-0.92) and adequate-to-excellent interday (ICC 0.61-0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17-0.42 intraday, 0.37-0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies.ConclusionThe close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique.
| S-EPMC6028741 | biostudies-literature
Project description:Besides stimulus intensities and interstimulus intervals (ISI), the electric field (E-field) orientation is known to affect both short-interval intracortical inhibition (SICI) and facilitation (SICF) in paired-pulse transcranial magnetic stimulation (TMS). However, it has yet to be established how distinct orientations of the conditioning (CS) and test stimuli (TS) affect the SICI and SICF generation. With the use of a multi-channel TMS transducer that provides electronic control of the stimulus orientation and intensity, we aimed to investigate how changes in the CS and TS orientation affect the strength of SICI and SICF. We hypothesized that the CS orientation would play a major role for SICF than for SICI, whereas the CS intensity would be more critical for SICI than for SICF. In eight healthy subjects, we tested two ISIs (1.5 and 2.7 ms), two CS and TS orientations (anteromedial (AM) and posteromedial (PM)), and four CS intensities (50, 70, 90, and 110% of the resting motor threshold (RMT)). The TS intensity was fixed at 110% RMT. The intensities were adjusted to the corresponding RMT in the AM and PM orientations. SICI and SICF were observed in all tested CS and TS orientations. SICI depended on the CS intensity in a U-shaped manner in any combination of the CS and TS orientations. With 70% and 90% RMT CS intensities, stronger PM-oriented CS induced stronger inhibition than weaker AM-oriented CS. Similar SICF was observed for any CS orientation. Neither SICI nor SICF depended on the TS orientation. We demonstrated that SICI and SICF could be elicited by the CS perpendicular to the TS, which indicates that these stimuli affected either overlapping or strongly connected neuronal populations. We concluded that SICI is primarily sensitive to the CS intensity and that CS intensity adjustment resulted in similar SICF for different CS orientations.
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Project description:Short-interval intracortical inhibition (SICI) represents an inhibitory phenomenon acting at the cortical level. However, SICI estimation is based on the amplitude of a motor-evoked potential (MEP), which depends on the discharge of spinal motoneurones and the generation of compound muscle action potential (M-wave). In this study, we underpin the importance of taking into account the proportion of spinal motoneurones that are activated or not when investigating the SICI of the right flexor carpi radialis (normalization with maximal M-wave (Mmax) and MEPtest, respectively), in 15 healthy subjects. We probed SICI changes according to various MEPtest amplitudes that were modulated actively (four levels of muscle contraction: rest, 10%, 20% and 30% of maximal voluntary contraction (MVC)) and passively (two intensities of test transcranial magnetic stimulation (TMS): 120 and 130% of motor thresholds). When normalized to MEPtest, SICI remained unchanged by stimulation intensity and only decreased at 30% of MVC when compared with rest. However, when normalized to Mmax, we provided the first evidence of a strong individual relationship between SICI and MEPtest, which was ultimately independent from experimental conditions (muscle states and TMS intensities). Under similar experimental conditions, it is thus possible to predict SICI individually from a specific level of corticospinal excitability in healthy subjects.
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Project description:ObjectiveProgressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)-induced long-interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short-interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1.MethodsTMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3 ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed.ResultsThe study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho = 0.872; p < .001) and SICI (rho = 0.689; p = .006).SignificanceOur results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.
| S-EPMC10107775 | biostudies-literature
Project description:BackgroundAuditory steady-state response (ASSR) paradigms have consistently demonstrated gamma band abnormalities in schizophrenia at a 40-Hz driving frequency with both electroencephalography (EEG) and magnetoencephalography (MEG). Various time-frequency measures have been used to assess the 40-Hz ASSR, including evoked power, single trial total power, phase-locking factor (PLF), and phase-locking angle (PLA). While both EEG and MEG studies have shown power and PLF ASSR measures to exhibit excellent test-retest reliability in healthy adults, the reliability of these measures in patients with schizophrenia has not been determined.MethodsASSRs were obtained by recording EEG data during presentation of repeated 20-Hz, 30-Hz and 40-Hz auditory click trains from nine schizophrenia patients (SZ) and nine healthy controls (HC) tested on two occasions. Similar ASSR data were collected from a separate group of 30 HC on two to three test occasions. A subset of these HC subjects had EEG recordings during two tasks, passively listening and actively attending to click train stimuli. Evoked power, total power, PLF, and PLA were calculated following Morlet wavelet time-frequency decomposition of EEG data and test-retest generalizability (G) coefficients were calculated for each ASSR condition, time-frequency measure, and subject group.ResultsG-coefficients ranged from good to excellent (> 0.6) for most 40-Hz time-frequency measures and participant groups, whereas 20-Hz G-coefficients were much more variable. Importantly, test-retest reliability was excellent for the various 40-Hz ASSR measures in SZ, similar to reliabilities in HC. Active attention to click train stimuli modestly reduced G-coefficients in HC relative to the passive listening condition.DiscussionThe excellent test-retest reliability of 40-Hz ASSR measures replicates previous EEG and MEG studies. PLA, a relatively new time-frequency measure, was shown for the first time to have excellent reliability, comparable to power and PLF measures. Excellent reliability of 40 Hz ASSR measures in SZ supports their use in clinical trials and longitudinal observational studies.
| S-EPMC6587022 | biostudies-literature
Project description:ObjectiveTo establish if induced current direction across the motor cortex alters the sensitivity of transcranial magnetic stimulation (TMS)-evoked short-interval intracortical inhibition (SICI) as an ALS biomarker.MethodsThreshold tracking-TMS was undertaken in 35 people with ALS and 39 controls. Using a coil orientation which induces posterior-anterior (PA)-directed current across the motor cortex, SICI (1 ms and 3 ms interstimulus intervals) and intracortical facilitation (ICF, 10 ms interstimulus interval) were recorded. SICI3ms was also recorded using a coil orientation which induces anterior-posterior (AP)-directed current across the motor cortex.ResultsAt group level, SICI3ms-PA (AUROC = 0.7), SICI3ms-AP (AUROC = 0.8) and SICI1ms (AUROC = 0.66) were substantially lower in those with ALS, although there was considerable interindividual heterogeneity. Averaging across interstimulus intervals (ISIs) marginally improved SICIPA sensitivity (AUROC = 0.76). Averaging SICI values across ISIs and orientations into a single SICI measure did not substantially improve sensitivity (AUROC = 0.81) compared to SICI3ms-AP alone. SICI3ms-AP and SICI3ms-PA did not significantly correlate (rho = 0.19, p = 0.313), while SICI1ms-PA and SICI3ms-PA did (rho = 0.37, p = 0.006). Further, those with ALS with the lowest SICI3ms-PA were not those with the lowest SICI3ms-AP. ICF was similar between groups (AUROC = 0.50).ConclusionsSICIPA and SICIAP are uncorrelated measures of motor cortical inhibitory functions which are useful as distinct, unequally affected, measures of disinhibition in ALS.SignificanceExamining both SICIPA and SICIAP may facilitate more comprehensive characterisation of motor cortical disinhibition in ALS.
| S-EPMC11002888 | biostudies-literature
Project description:ObjectiveTo evaluate the convergent validity of the six-minute stepper test (6MST) with the variables used in the diagnosis of sarcopenia (appendicular muscle mass, handgrip strength and six-meter gait speed test), as well as to evaluate test-retest reliability and safety when applied to hospitalized elderly patients. Finally, we aimed to compare the performance in the 6MST between hospitalized elderly patients and healthy elderly from the community.Materials and methodsObservational and cross-sectional study. Elderly patients admitted to a private hospital and healthy elderly from the community were recruited. On the first day, the patients included underwent the following assessments: anthropometric, handgrip strength (HGS), six-meter gait speed test (6GST) and 6MST. On the second day, before breakfast, patients underwent body composition assessment. The healthy elderly were evaluated on a single day and performed only anthropometric assessment and 6MST.Results30 hospitalized patients (age 71.0±7.9 years) and 15 healthy elderly (age 68.1±5.8 years) were included. There was a high correlation of 6MST with 6GST (r = 0.78; p<0.001), moderate correlation with HGS (r = 0.59; p<0.001) and low correlation with appendicular muscle mass (r = 0.45; p = 0.01). There was no statistical difference between the first and second 6MST performed by hospitalized elderly (196.2±91.0 cycles vs. 191.3±103.7 cycles; p = 0.66), in addition to an excellent agreement between these measures (ICC = 0.90; 95% IC 0.78-0.95). Only one adverse event (3.3%) occurred in the sample.Conclusion6MST showed convergent validity with the functional variables used in the diagnosis of sarcopenia. In addition, excellent test-retest reliability was observed, which indicates the need for a single assessment in hospitalized elderly patients. The prevalence of adverse events during the application of the test is low, without resulting in clinical symptoms; therefore, the test is considered safe for this population. In addition, hospitalized elderly patients perform worse in the 6MST compared to healthy elderly from the community.
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