Autonomic dysfunction is common in multiple sclerosis (MS), and autonomic symptoms are independent contributors to MS fatigue. Aerobic training (AT) has been shown to reduce fatigue severity and to promote functional network reorganization in MS. We explored resting-state (RS) functional connectivity (FC) of the central autonomic network (CAN) in MS, its relationship with fatigue severity, and its modifications after AT vs non-AT. Seventy-five patients with MS (38 with relapsing-remitting [RR] and 37 with progressive [P]) underwent 3T RS functional MRI at baseline and at the end of AT (24 training sessions, 2-3 times per week for 2-3 months) or non-AT of equivalent duration. Sixty-seven matched healthy controls (HCs) served as a reference for baseline RS FC. At both visits, all patients were assessed using the Modified Fatigue Impact Scale (MFIS). Seed-based RS FC used core CAN modulatory regions: left/right ventromedial prefrontal cortex (vmPFC), mid-cingulate cortex (MCC), amygdala, hypothalamus, and anterior and posterior insula. Compared with HCs, patients with MS showed increased baseline RS FC of the right amygdala, anterior insula, and vmPFC with superior frontal gyri, precentral gyri and right precuneus. Considering disease phenotype, we found a divergent behavior of baseline RS FC in the interaction analysis (p < 0.05, corrected), with patients with RRMS showing predominantly increased RS FC of the amygdala, anterior insula, and MCC with supplementary motor areas (SMAs) and deep gray matter, whereas patients with PMS showed widespread baseline RS FC decrease, particularly involving posterior insula connections with the cerebellum and parietal regions, and MCC connections with frontotemporal areas. In patients with RRMS, increased baseline CAN RS FC inversely correlated with fatigue severity (r = range -0.33/-0.54, p range = 0.046/0.001), while no significant correlations were found in patients with PMS. In patients who underwent AT, decreased hypothalamic network RS FC at follow-up vs baseline was observed (p < 0.001, significant time-by-treatment interaction vs non-AT), with more prominent changes in patients with RRMS compared with patients with PMS. No correlations were found between longitudinal RS FC modifications and concomitant fatigue changes. CAN dysregulation is present in MS, with distinct RS FC abnormalities characterizing patients with RRMS and PMS and correlating with fatigue severity. AT modulates CAN RS FC, particularly in patients with RRMS.

Resting-state functional connectivity in HIV - Findings from the ENIGMA HIV working group.

Effects of escitalopram on resting-state functional connectivity in comorbid depressive and anxious adolescents.

Associations between childhood trauma and amygdala- and insula-centered resting-state functional connectivity in alcohol use disorder.

Resting-state functional connectivity correlates of emotional memory control under cognitive load in subclinical anxiety.

BackgroundAmong aging individuals, some develop Alzheimer's disease (AD) while others remain cognitively stable. Understanding how structural and functional brain changes interact, could clarify this heterogeneity particularly among individuals at increased risk for AD.ObjectiveThis study aims to explore how structure-function connectivity changes relate to subsequent long-term cognitive trajectories in older adults with SMC and varying amyloid burden.MethodsWe analyzed data from the INSIGHT-preAD cohort, which includes older individuals with subjective cognitive complaints followed neuropsychologically over five years. Multiplex connectome integrating resting-state EEG functional connectivity and diffusion-weighted imaging-based structural connectivity was used to characterize brain network organization. We computed the multiplex participation coefficient (PC) as an index of structure-function similarity and examined its association with individual cognitive trajectories across the follow-up period.ResultsSignificant differences in multiplex connectivity were observed among amyloid positive participants who later progressed to AD compared to amyloid positive stable (e.g., non-progressors) and amyloid negative controls. Specifically, higher PC values in the delta band were observed in amyloid positive individuals who later developed AD. This pattern, particularly within the default mode network, was associated with subsequent cognitive decline suggesting that delta band structure-function similarity may represent a potential candidate marker of cognitive vulnerability and progression in AD.ConclusionsMost studies investigating AD have primarily examined functional or structural connectivity separately. By integrating both modalities using a multiplex approach, our study provides interesting preliminary evidence that structure-function connectivity may capture network-level changes associated with cognitive trajectories along AD continuum.

Regional structural-functional coupling alterations associated with subjective sleep quality in young adults.

Suicide remains a critical global public health issue, and the ideation-to-action framework suggests that suicidal ideation and attempts involve distinct processes. However, the neurobiological mechanisms underlying the transition from suicidal ideation (SI) to suicide attempts (SA) have not been fully understood, particularly in clinically heterogeneous psychiatric populations. This study aimed to investigate whether resting-state electroencephalography (EEG) connectivity patterns can differentiate suicidal ideation and attempts. Resting-state functional connectivity as measured by EEG was analyzed among 244 participants, categorized into three groups: non-suicidal, suicidal ideation only, and suicide attempt. The analysis focused on the default mode network (DMN) and inhibition network using source-level analysis. Group differences were examined first in the full sample and then repeated in the depressive disorder subgroup (N = 78) to evaluate whether findings were more evident within a diagnostically more homogeneous context. In the full sample, no significant group differences survived either global or network-based false discovery rate correction in either network. In the depressive disorder subgroup, however, the suicidal group (SI + SA) showed reduced theta-band functional connectivity within the DMN, particularly between the dorsomedial prefrontal cortex and right inferior parietal lobule, compared with the non-suicidal group. No significant differences were observed between the SI-only and SA groups, and no significant findings emerged in the inhibition network. Altered DMN connectivity may be relevant to suicidal ideation in depressive disorders, while inhibition-network connectivity did not differentiate SA from SI-only. These findings are broadly consistent with aspects of the ideation-to-action framework and highlight the importance of considering diagnostic context when interpreting resting-state EEG findings in suicide research.

Effects of riluzole on excitation-inhibition imbalance and functional connectivity in 22q11.2 deletion syndrome: a multimodal 7-Tesla MRI study.

The global prevalence of problematic use of the internet (PUI) has increased over time, particularly among youth. To enhance the efficacy of treatments and identify personalized intervention targets, it is important to classify subtypes based on differences in underlying mechanisms rather than solely on symptom severity. This study aimed to identify reliable subtypes of PUI among youth by examining three neurofunctional domains commonly implicated in addictive behaviors-reward processing, negative emotionality, and executive function - and to assess how the identified subtypes differed regarding clinical characteristics and resting-state functional connectivity. Data were drawn from the Healthy Brain Network (HBN) study, comprising 484 children and adolescents (ages 6-21; 37.4% female), including 242 individuals with PUI and 242 matched controls. Latent profile analysis, along with sensitivity analyses, was conducted on phenotypic data reflecting the three addiction-related domains. The resulting subtypes were then evaluated for clinical characteristics and resting-state brain functional connectivity to consider their clinical and biological relevance. Three stable PUI subtypes were identified: a 'High approach with low executive function' subtype characterized by steeper delay discounting and poorer executive function, frequently co-occurring with learning disorders (n = 20); a 'Negative emotionality' subtype with elevated negative affect, frequently co-occurring with affective disorders (n = 37); an 'Emotional stress' subtype that only exhibited higher negative affect compared to matched controls and showed no marked dysfunction across other domains (n = 185). Furthermore, each subtype demonstrated distinct patterns of resting-state functional connectivity. The findings provide empirical evidence that youth with PUI are heterogeneous across three core neurofunctional domains, offering insights for the development of more tailored, subtype-specific interventions.

Growing evidence in preclinical and clinical models suggests that prenatal cannabis exposure (PCE) is associated with changes in brain functioning and behavior. This observational longitudinal study examines these associations using biological measures of PCE in a sample of Black mother-infant dyads (N=42), who have historically been underrepresented in developmental neuroimaging studies. Maternal urine samples collected during pregnancy (8-14 weeks of gestation) were assayed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC) metabolites, providing a biologically verified measure of prenatal cannabis exposure. Newborns (57% female) completed a resting-state fMRI scan and were assessed using the NICU Network Neurobehavioral Scale at approximately 1 month postpartum. We performed voxelwise seed connectivity analyses using seeds in the bilateral hippocampus, insula, and caudate. We found that COOH-THC levels in early pregnancy were significantly associated with altered connectivity patterns in the hippocampus, insula, and caudate in infants. These functional connectivity patterns, however, were not correlated with indices of newborn neurobehavior. These preliminary results suggest that cannabis exposure early in pregnancy may impact neural connectivity shortly after birth, with effects that withstand the influence of co-occurring maternal psychosocial factors.

Neuroimaging is prevalent in psychiatric research, but there is limited evidence that it improves clinical outcomes. Functional connectivity neuroimaging was recently used to target individualized brain circuits with accelerated transcranial magnetic stimulation (aTMS), with rapid antidepressant effects and US Food and Drug Administration clearance, but the importance of connectivity-based targeting remains unclear. To estimate the effect size of connectivity- vs scalp-based targeting of aTMS for treatment-resistant depression. This randomized clinical trial comparing connectivity- to scalp-based aTMS treatment was conducted between July 2023 and March 2025 with the primary outcome assessed at 1 month posttreatment and follow-up every 3 months for 1 year. Participants, TMS technicians, and study physicians were blinded. The study took place at the Center for Brain Circuit Therapeutics at Mass General Brigham and Harvard Medical School in Boston, Massachusetts. Forty adults aged 22 to 80 years with a primary diagnosis of major depressive disorder with moderate to severe depression per Montgomery-Åsberg Depression Rating Scale (MADRS) score and moderate to severe treatment resistance per Maudsley Staging Method were included. Key exclusion criteria included contraindications to TMS or magnetic resonance imaging, primary psychiatric diagnoses other than major depressive disorder or anxiety disorders, recent rapid-acting antidepressant treatments, and significant neurological or substance use disorders. All participants underwent a 41-minute multiecho resting-state functional connectivity scan prior to aTMS, and half of them received treatment guided by these data. The connectivity-based target was defined as the left dorsolateral prefrontal cortex region with the greatest correlation to a published and publicly available convergent depression circuit. This circuit includes multiple brain regions linked to depression, including negative connectivity to the subgenual cingulate cortex. The scalp-based target was identified with the Beam F3 method. MADRS score 1 month after treatment, adjusted for baseline. In total, 40 participants (22 female [55%]; mean [SD] age, 45.7 [15.2] years) were randomized and treated. The median (IQR) MADRS score reduction was 24 (19-28) vs 18 (10-23) points with connectivity- vs scalp-based targeting, respectively (P = .02). Connectivity-based targeting had an effect size of 0.8 (Cohen d analog) and 95% CI of 0.26-1.54, with a number needed to scan of 5 individuals. Individualized targets were reproducible within an individual (4.47 mm split-half distance) and different between individuals (12.97 mm) (P < .001). In this randomized clinical trial, individualized, connectivity-based targeting of the convergent depression circuit enhanced the antidepressant effects of high-dose aTMS. These results could facilitate cost-effectiveness analyses and help to power a confirmatory efficacy trial. ClinicalTrials.gov Identifier: NCT05680727.

Association of APOE rs405509 (-219 T/G) with multidimensional cognitive function, brain structure, and resting-state networks in Chinese community-dwelling older adults.

Cyclical alcohol craving is linked with estradiol-based modulation of ventral tegmental area functional connectivity and is blunted by childhood maltreatment.

Shifts in the brain sex continuum in major depressive disorder: Evidence for a persistent neurobiological marker.

Ebselen has been shown to induce a positive emotional processing bias and brain neurochemistry in healthy volunteers. However, little is known about its effects on resting-state functional connectivity (rs-FC) in depressed patients who show inadequate responses to standard antidepressants. The study aimed to investigate the effect of ebselen as an add-on treatment on rs-FC in this population. We conducted a randomised, double-blind, placebo-controlled trial involving depressed patients who were not responsive to their current treatment. Participants received either ebselen 600mg twice daily or placebo for seven days. Resting-state functional magnetic resonance imaging was conducted at baseline and on day seven. Resting-state data were analysed using seed-based analysis and independent component analysis. Greater changes in rs-FC between the pregenual anterior cingulate cortex and the cerebellum were observed in ebselen than in placebo, but became negligible after corrections for multiple comparisons. We identified treatment effects within visual networks and between visual and sensorimotor networks, however, these did not survive correction for multiple comparisons. Short-term ebselen treatment in depressed patients with inadequate antidepressant responses did not produce significant changes in rs-FC. These findings may reflect limitations related to the short treatment duration and small and heterogeneous sample.

Reorganization of brain-autonomic integration in alcohol use disorder.

Repetitive transcranial magnetic stimulation combined with Tai Chi improves working memory in older adults with sleep disorders and mild cognitive impairment: An fMRI-based randomized controlled trial.

Cognitive ability in childhood predicts adolescent structural and functional brain development: A longitudinal study.

To investigate the changes in cognition, anaerobic power, and corresponding cerebral cortex activation characteristics and functional connectivity (FC) following fatigue induced by an acute simulated tennis match. Eighteen healthy adult male tennis enthusiasts (tennis experience: 5 ± 1.4 years, age: 24.5 ± 2.4 years) participated in this study. The participants performed a 90-minute simulated tennis match to induce fatigue. Behavioral data from 2-back task and Wingate tests were collected at three time points: pre-fatigue, immediately post-fatigue, and 1-hour post-fatigue. Functional near-infrared spectroscopy (fNIRS) was simultaneously used to measure oxyhemoglobin (HbO) levels and 3-minute resting-state FC in the frontal and parietal lobes. At 1-hour post-fatigue, 2-back reaction times (RT) increased compared to pre-fatigue, with no significant change in accuracy. During the 2-back task, HbO levels decreased in the right dorsolateral prefrontal cortex (R-DLPFC) at both post-fatigue time points, whereas frontopolar area (FPA) reductions were more evident at 1-hour post-fatigue. The R-DLPFC was found to play a more critical role in cognitive tasks than the L-DLPFC, and an increase in RT was observed to be negatively correlated with HbO in the R-DLPFC. Peak power and average power output declined immediately and 1-hour post-fatigue compared to pre-fatigue. During the Wingate test, HbO reductions were observed in the R-DLPFC and R-PMSMC at both post-fatigue time points, and in the L-PMSMC at 1-hour post-fatigue. FC decreased more prominently 1-hour post-fatigue, marked by reduced connection strength in specific regions of interest and channels. The decline in cognitive and physical performance following tennis-induced fatigue is accompanied by decreased cerebral HbO and FC. This reduction in HbO may indicate a decreased supply of oxygen to the brain and lower levels of brain activation, which could be crucial factors influencing both central and peripheral fatigue during tennis fatigue.