MEG Microstates: An Investigation of Underlying Brain Sources and Potential Neurophysiological Processes.

Microstates are transient scalp configurations of brain activity measured by electroencephalography (EEG). The application of microstate analysis in magnetoencephalography (MEG) data remains challenging. In one MEG dataset (N = 113), we aimed to identify MEG microstates at rest, explore their brain sources, and relate them to changes in brain activity during open-eyes (ROE) or closed-eyes resting state (RCE) and an auditory Mismatch Negativity (MMN) task. In another dataset of simultaneously recorded EEG-MEG data (N = 21), we investigated the association between MEG and EEG microstates. Six MEG microstates (mMS) provided the best clustering of resting-state activity, each linked to different brain sources: mMS 1-2: left/right occipito-parietal; mMS 3: fronto-temporal; mMS 4: centro-medial; mMS 5-6: left/right fronto-parietal. Increases in occipital alpha power in RCE relative to ROE correlated with greater mMS 1-2 time coverage (τbs < 0.20, ps > .002), while the lateralization of deviance detection in MMN was associated with mMS 5-6 time coverage (τbs < 0.16, ps > .012). No temporal correlation was found between EEG and MEG microstates (ps > .05), despite some overlap in brain sources and global explained variance between mMS 2-3 and EEG microstates B-C (rs > 0.60, ps < .002). Hence, the MEG signal can be decomposed into microstates, but mMS brain activity clustering captures phenomena different from EEG microstates. Source reconstruction and task-related modulations link mMS to large-scale networks and localized activities. Thus, mMSs offer insights into brain dynamics and task-specific processes, complementing EEG microstates in studying physiological and dysfunctional brain activity.

Reduced magnetic mismatch negativity: a shared deficit in psychosis and related risk.

BACKGROUND: Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). METHODS: Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). RESULTS: The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. CONCLUSIONS: Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear. Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs. Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs. Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs. Results: Across 11 head-to-head RCTs (n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99). Conclusion: LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed. Trial registration: CRD42023407120 (PROSPERO).

OBJECTIVE: We aimed to uncover whether LAIs or regular antipsychotic pills demonstrate better outcomes over the medium and long term for individuals in the early stages of schizophrenia. METHOD: We scrutinized several studies comparing LAIs to regular pills in treating early-stage schizophrenia. Employing a combined analysis, we assessed factors such as preventing relapses and hospitalizations, as well as patient treatment adherence. DESIGN: We combined different study results in one unique analysis. We delved into whether LAIs surpassed regular pills in preventing relapses and hospitalizations and in patient treatment adherence. RESULTS: In our study of 11 trials involving over 2000 participants, we observed that LAIs and regular antipsychotic pills were generally comparable regarding preventing relapses, hospitalizations, and treatment adherence. However, on closer inspection, LAIs appeared slightly more effective for specific groups in the early stages of schizophrenia. CONCLUSION: While LAIs and regular antipsychotic pills showed similar results for most individuals in the early stages of schizophrenia, our findings hint at the possibility that LAIs might have a slight edge for certain groups. Nevertheless, we emphasize the need for more high-quality studies to gain a clearer understanding. REGISTRATION: This study is registered under CRD42023407120 (PROSPERO).

Comparing long-acting injections and pills for early schizophrenia: a study review and combined analysis Background: We explored whether antipsychotics long-acting injections (LAIs) might outperform regular antipsychotics pills for people dealing with early-stage conditions like schizophrenia. While LAIs have clear benefits for those with long-term challenges, their effectiveness for those just starting to grapple with these issues is less certain.