Resting-State fMRI Functional Connectivity Alterations in Drug-Resistant Epilepsy Compared to Well-Controlled Epilepsy and Healthy Controls

Alterations in static and dynamic intrinsic brain local connectivity and associated molecular analysis in drug-naïve first-episode schizophrenia: Insights from resting-state functional magnetic resonance imaging.

Schizophrenia is a severe psychiatric disorder marked by widespread brain abnormalities. Recent studies suggest that pathological changes may originate from focal 'epicenter' regions and subsequently spread to other brain areas strongly connected to them. Investigating drug-naïve first-episode schizophrenia (dn-FES) patients may help characterize early-stage regional functional abnormalities and their potential neurochemical underpinnings. Resting-state functional magnetic resonance imaging data were acquired from 50 dn-FES patients and 50 age- and sex-matched healthy controls (HCs). Static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were compared between groups, and correlations with psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). We further used the JuSpace toolbox to test whether spatial patterns of ReHo alterations were associated with specific neurotransmitter receptor/transporter densities. Compared with HCs, dn-FES patients showed reduced sReHo in the bilateral postcentral/precentral gyri, bilateral paracentral lobules and right supplementary motor area, and increased dReHo in the left lingual gyrus. sReHo in the right postcentral gyrus was inversely correlated with PANSS positive scores, whereas dReHo in the left lingual gyrus was negatively correlated with PANSS general scores. Schizophrenia-related sReHo alterations showed significant spatial associations with serotonergic, dopaminergic, noradrenergic and cholinergic systems, whereas dReHo alterations were associated with serotonergic, dopaminergic, cannabinoid and opioid systems. Taken together, this study identifies abnormal static and dynamic local functional connectivity in sensorimotor and visual regions in drug-naïve first-episode schizophrenia, and the spatial correspondence between these alterations and receptor/transporter distributions may offer insight into the molecular substrates associated with these functional abnormalities.

Abnormal Local Brain Activity in SCA3 Patients with Cognitive Impairment: A Resting-State Functional MRI Study

Nucleus basalis functional connectivity aberrations in temporal lobe epilepsy and improvements after successful epilepsy surgery.

Successful TLE surgery is associated with partial restoration of cholinergic arousal network connectivity, supporting the idea that seizure cessation enables recovery of brain networks disrupted by recurrent seizures.

Characterizing functional connectivity alterations in functional/ dissociative seizures using resting-state and naturalistic fMRI.

OBJECTIVE This study investigates alterations in brain functional networks in patients with functional/dissociative seizures (FDS) using a novel functional connectivity framework, with the goal of showing network-level biomarkers that may differentiate FDS from healthy controls. METHODS We conducted a 7-Tesla fMRI study involving 11 patients with FDS and 11 healthy controls (HC) gotten during both resting-state (rs) and a naturalistic-stimulus (ns) movie paradigm. Functional connectivity) was computed using parcel-wise Pearson correlations, and centrality measures, including eigenvector centrality, were derived to assess network influence. Group differences were evaluated using motion-controlled general linear models A sensitivity index found key ROIs, which were used in cross-validated logistic regression models. The classification model uses eigenvector centrality with 5-fold cross-validation. RESULTS FDS patients showed consistent alterations in eigenvector centrality across both resting-state and naturalistic-stimulus fMRI, particularly within limbic, somatomotor, and ventral attention network. Three key ROIs during rest and fifteen during naturalistic stimulation yielded high classification accuracies (96% and 93%, respectively). Several hubs found in the movie condition remained altered at rest. Logistic regression models using these network features distinguished FDS from controls, though findings require cautious interpretation due to sample size limitations. CONCLUSIONS Using high-field fMRI and a novel connectivity analysis, this study found abnormal network hubs across multiple systems in FDS. These findings support a predictive processing model and offer preliminary biomarkers to improve FDS differentiation, pending validation in larger cohorts.

Divergent cortical-subcortical intrinsic neural timescales in first-episode drug-naïve or minimally treated schizophrenia.

BACKGROUND The neuropathological mechanisms of schizophrenia remain unclear. Intrinsic neural timescale (INT) reflects the temporal organization of neural activity. This study aimed to characterize INT alterations in patients with first-episode schizophrenia who were drug-naïve or minimally treated, while minimizing confounding effects of chronic illness and medication exposure. METHODS Resting-state fMRI data were collected from 123 first-episode, drug-naïve or minimally treated schizophrenia patients and 102 matched healthy controls. INT values were derived from the autocorrelation function of the fMRI signal. Group differences in INT were assessed using analysis of covariance (ANCOVA), controlling for age, gender and scanner site. Additional analyses included correlation analyses, gene annotation and enrichment analyses, and spatial correlation analyses. RESULTS Patients exhibited a divergent cortical-subcortical pattern, characterized by reduced cortical INT and prolonged subcortical INT. Compared with healthy controls, patients showed significant INT alterations in 13 regions of interest (p-fdr < 0.05), predominantly involving the default mode network (5 regions) and subcortical network (4 regions), as well as the sensorimotor network, memory retrieval network, salience network, and ventral attention network. Regions with altered INT were enriched for synapse-related genes, and their spatial distribution was correlated with cerebral blood flow. CONCLUSIONS Our findings show that first-episode drug-naïve or minimally treated schizophrenia patients are characterized by disrupted intrinsic neural timescales with distinct cortical-subcortical alterations. These abnormalities may be related to cerebral perfusion, synaptic function and symptom severity. The distinct cortical-subcortical alterations of INTs may represent a candidate neurobiological marker of early-stage schizophrenia.

Uncovering Individual Language Vulnerability in Epilepsy Through Functional Connectivity Laterality.

BACKGROUND Language processing is organized in brain networks, generally lateralized to the left hemisphere. In clinical routine, task-based functional MRI (fMRI) is the gold standard for non-invasive evaluation of language lateralization. However, standard fMRI does not account for the individual heterogeneity of language networks. fMRI-based functional connectivity analysis (FCA) has addressed this shortcoming by identifying correlates of dysfunctional language networks in epilepsy patients. In order to individualize FCA, translation of group-based network analysis to individual epilepsy patients is necessary. Here, we introduce the functional connectivity laterality index (LIFC) as a potential clinical parameter. METHODS This retrospective study included adults with unilateral temporal lobe epilepsy (TLE) who underwent task-based fMRI and a control group. To account for individual variations, fMRI was performed at a 3T scanner and processed entirely in native space. Laterality indices were computed from both activation maps and seed-based functional connectivity across frontal, temporal, and combined language regions. Group comparisons and associations with neuropsychological language performance were analysed. RESULTS Forty patients with unilateral TLE and 25 healthy controls were included. Groups were comparable in terms of sex, handedness, imaging findings, and epilepsy duration, although the controls were younger. Classical LI showed predominantly left-lateralization, while LIFC showed mostly bilateral language lateralization. Neuropsychological performance did not differ between TLE-left and TLE-right patients. While a difference in semantic fluency was initially observed, it did not survive correction for multiple comparisons. However, analyses based on functional network organization revealed a critical pattern: Patients with language networks lateralized to the seizure side-as quantified by LIFC-showed significantly poorer semantic fluency and lower composite language scores. This potential clinically relevant result was exclusive to FCA and was not captured by activation data alone. CONCLUSION Our findings suggest an individual vulnerability of language networks to seizure burden, although this uncorrected, exploratory finding requires replication in larger, independent samples. Incorporating functional connectivity measures into presurgical clinical fMRI analysis may enhance our ability to predict and protect language function in patients with TLE by prioritizing further therapies or surgical interventions for those at higher risk of language decline.