Most recent paper

Biol Psychiatry Glob Open Sci. 2026 Jun 10;6(5):100768. doi: 10.1016/j.bpsgos.2026.100768. eCollection 2026 Sep.

ABSTRACT

BACKGROUND: Disrupted maturation of functional brain networks has been increasingly linked to elevated risk of psychosis, but the spatiotemporal characteristics of these deviations remain unclear. We used longitudinal connectome fingerprinting and jointly analyzed the functional connectivity (FC) and intraclass correlation coefficient (ICC) to obtain age-dependent trajectories of functional brain organization in 22q11.2 deletion syndrome (22q11DS), a high-risk model for psychosis.

METHODS: Resting-state functional magnetic resonance imaging from 62 individuals with 22q11DS and 63 control participants (ages 8-30 years, 2-5 visits) were analyzed. Patients were stratified by the presence or absence of positive psychotic symptoms (PPSs) [PPS(+), PPS(-)]. The FC and ICC characterization of connectome fingerprints were projected onto a joint principal component (PC) space, yielding 3 orthogonal axes of maturation: PC1 (sensory-association axis), PC2 (emotional-cognitive balance), and PC3 (executive-sensory control). Longitudinal trajectories along these axes characterized the directionality and coordination of connectome maturation.

RESULTS: Control participants showed a clear decrease in identifiability and stability during adolescence, followed by recovery into adulthood, reflecting coordinated, direct maturation along all 3 axes. PPS(-) individuals exhibited a partial decrease and subsequent recovery, preserving adaptive reorganization along PC3. In contrast, PPS(+) participants displayed disorganized and irregular trajectories in the PC space and a decline in PC3, indicating disrupted temporal coordination of network maturation and fragmented executive-sensory integration.

CONCLUSIONS: Loss of developmental synchrony in FC was associated with psychosis vulnerability in 22q11DS. PC analysis-based multiaxis mapping revealed that resilience and vulnerability are determined by the direction and synchrony of brain maturation rather than by stability alone, highlighting a novel marker for tracking neurodevelopmental risk across psychiatric disorders.

PMID:42502641 | PMC:PMC13400943 | DOI:10.1016/j.bpsgos.2026.100768

J Mood Anxiety Disord. 2026 Jul 10;15:100192. doi: 10.1016/j.xjmad.2026.100192. eCollection 2026 Sep.

ABSTRACT

BACKGROUND: Individuals with bipolar disorder spend significantly more time depressed than manic, and treatment alternatives for treatment-resistant patients are greatly needed. Although the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) intermittent theta-burst stimulation (iTBS) protocol has shown efficacy in unipolar depression, its utility in bipolar depression remains largely unexplored. This study aims to assess the feasibility and safety of SAINT in patients with bipolar I depression that have failed to respond to a first-line treatment and examine underlying neural mechanisms of treatment response.

METHODS: Ten participants with bipolar I disorder underwent a modified SAINT protocol in this open-label study. Depressive and manic symptoms were assessed throughout. Personalized left dorsolateral prefrontal cortex (DLPFC) stimulation targets exhibiting negative resting-state connectivity with the subgenual anterior cingulate cortex (sgACC) were generated using resting-state functional MRI. We then investigated changes in resting-state (DLPFC and sgACC) seed-to-whole brain connectivity, and its relationship to treatment response.

RESULTS: Immediately post-treatment, depressive symptoms decreased by an average of 56.7 (SD=19.7%)%. Following treatment, participants exhibited increased connectivity between sgACC and two bilateral frontal pole clusters. Greater reductions in depressive severity were significantly associated with increased negative connectivity between left DLPFC target seed and four clusters in prefrontal and temporal cortices.

CONCLUSION: SAINT iTBS was well-tolerated in a bipolar I depression sample and associated with sgACC functional connectivity changes. Increased negative connectivity between the DLPFC target and prefrontal/temporal cortex was associated with treatment response. Larger, sham-controlled studies are needed to confirm these findings and explore predictors of treatment response in bipolar depression.

PMID:42502622 | PMC:PMC13400662 | DOI:10.1016/j.xjmad.2026.100192

Brain Stimul. 2026 Jul 25:103173. doi: 10.1016/j.brs.2026.103173. Online ahead of print.

ABSTRACT

BACKGROUND: Targeting methods for repetitive transcranial magnetic stimulation (rTMS) in patients with depression now include individual functional magnetic resonance imaging (fMRI) scans to target specific functional connectivity (FC) patterns. Potential biomarkers of rTMS response include target FC with the subgenual anterior cingulate cortex (SGC) or the causal depression circuit (CDC), each of which may be candidates for individualized functional targets (iFTs). We retrospectively assessed the relationship of these two approaches to outcomes in secondary analyses of two large rTMS clinical trials.

METHODS: 501 subjects with moderate to severe depression underwent 4-6 weeks of daily rTMS to the left dorsolateral prefrontal cortex (DLPFC), targeted using neuronavigation to an optimized DLPFC-SGC-FC group-based functional target. Baseline resting-state scans were used to retrospectively compute iFTs using either SGC-DLPFC or CDC-DLPFC FC. Proximity (Euclidean distance) of the stimulated target to iFTs were correlated with outcomes. Electric field magnitude at iFTs was computed to capture non-linear stimulation propagation.

RESULTS: Most iFTs were within 2cm of their group-target. Proximity to either an SGC- or CDC-iFT was not associated with better outcomes. Sensitivity analyses accounting for treatment target FC, methodology, data quality, or treatment parameters did not change results. Electric field-based measures were highly similar to Euclidean distance and likewise showed no association with outcomes.

CONCLUSIONS: Under the specific fMRI acquisition parameters used, proximity to optimized DLPFC-SGC-iFTs was not associated with better outcomes in patients receiving neuronavigated rTMS to an optimized DLPFC-SGC group-target. Prospective randomized clinical trials definitively assessing the clinical utility of iFTs are warranted. .

PMID:42501968 | DOI:10.1016/j.brs.2026.103173

Brain Topogr. 2026 Jul 25;39(5):84. doi: 10.1007/s10548-026-01239-x.

ABSTRACT

The amygdala is a central hub for emotional processing, whose interactions with large-scale brain networks have been implicated in the pathophysiology of depression. Investigating how amygdala-centered connectivity relates to depression in a community-based sample, rather than focusing exclusively on patients with major depressive disorder, may provide broader insights into depression vulnerability. To this end, functional connectivity (via cross-correlation) and effective connectivity (via Granger causality) were computed using resting-state functional magnetic resonance imaging (fMRI) data from 161 adults obtained from the Nathan Kline Institute (NKI)/Rockland community sample. Subsequently, a behavior-guided windowed association analysis identified connectivity indicators correlated with depression severity (Beck Depression Inventory scores), whose contributions to depression prediction were subsequently ranked using machine learning based on a support vector machine. Specifically, higher Beck Depression Inventory (BDI) scores were associated with increased amygdala functional connectivity with the salience/ventral attention system and the dmPFC component of the default mode network, together with decreased connectivity involving dorsal attention, sensorimotor, and visual regions. Granger causality analyses further revealed predominantly reduced directional influences both to and from the amygdala, particularly between the amygdala and distributed default mode, salience/ventral attention, visual, and subcortical regions, suggesting weakened large-scale information exchange. Machine learning analyses identified amygdala-centered connectivity features, especially those involving the default mode and salience-related systems, as among the most informative predictors of depression severity. Overall, these findings delineate an amygdala-centered multi-system network pathology underlying depressive vulnerability, providing quantifiable neural signatures for early detection and potential targets for intervention.

PMID:42501214 | DOI:10.1007/s10548-026-01239-x

Cerebellum. 2026 Jul 25;25(4):119. doi: 10.1007/s12311-026-02061-8.

ABSTRACT

Cognitive impairment (CI) has been reported in spinocerebellar ataxia 3 (SCA3). However, the link between alterations in intrinsic brain activity and cognitive functions remains poorly understood. This study aimed to explore these alterations and their association with cognitive functions to elucidate the pathophysiological mechanisms underlying CI in SCA3. Eighty-four SCA3 patients and 41 healthy controls (HCs) were enrolled. Patients were classified into CI and non-CI groups based on their neuropsychological test performance relative to HCs. We calculated resting-state fMRI (rs-fMRI) metrics, including amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC), and compared them between the two patient groups. Whole-brain correlation analyses were used to explore the neural correlates of cognitive deficits by correlating rs-fMRI metrics with composite cognitive z-scores. Compared to SCA3 patients without CI, those with CI showed: (1) increased ALFF in fronto-striatal regions and decreased ALFF in the default mode network; (2) decreased fALFF in the dorsolateral prefrontal cortex but increased fALFF in the supplementary motor area and paracentral lobule; (3) increased ReHo in cerebellar cognitive regions; and (4) reduced DC in the left putamen, insula, and superior frontal gyrus. These alterations were primarily located within the cortico-striato-thalamo-cortical loop and cerebellar cognitive regions. Whole-brain correlation analyses confirmed that these rs-fMRI metric alterations correlated with cognitive performance. Our study revealed distinct patterns of spontaneous brain activity associated with cognitive impairment in SCA3. These findings provide novel imaging evidence for the pathophysiological mechanisms underlying cognitive decline in these patients.

PMID:42501193 | DOI:10.1007/s12311-026-02061-8

Am J Alzheimers Dis Other Demen. 2026 Jan-Dec;41:15333175261460967. doi: 10.1177/15333175261460967. Epub 2026 Jul 25.

ABSTRACT

BackgroundThis study aimed to investigate the correlation between multi-metric resting-state fMRI (rs-fMRI) changes and cognitive performance in amnestic mild cognitive impairment (aMCI), moving beyond single-metric analyses.MethodsForty aMCI patients and twenty healthy controls underwent 3.0T rs-fMRI and neurocognitive assessment (MoCA, DST). Multiple rs-fMRI metrics (ReHo, ALFF/fALFF, RSFC) were analyzed for their association with cognition.ResultsaMCI patients showed increased frontal ReHo, decreased ALFF in default mode network hubs, and reduced prefrontal-parietal-temporal RSFC. Frontal hyper-synchronization correlated negatively with cognitive scores, while DMN ALFF correlated positively.ConclusionsMulti-metric fMRI detects characteristic functional alterations in aMCI, indicating regional brain damage or compensatory changes linked to cognitive performance.

PMID:42501010 | DOI:10.1177/15333175261460967

Front Neurol. 2026 Jul 10;17:1849749. doi: 10.3389/fneur.2026.1849749. eCollection 2026.

ABSTRACT

BACKGROUND: Brainstem infarction is a clinically important subtype of posterior circulation infarction and is often associated with disability and poor functional recovery. Disease-specific therapeutic strategies remain limited, and rehabilitation-oriented evidence specifically targeting functional recovery in this population remains insufficient. Acupuncture has been studied and applied as an adjunctive approach for stroke rehabilitation in multiple regions; however, high-quality evidence for its use in brainstem infarction remains scarce. This trial primarily aims to evaluate whether adjunctive Shallow Acupuncture improves activities of daily living in patients with brainstem infarction; as an exploratory objective, it will examine associated neural changes assessed by resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI).

METHODS AND ANALYSIS: This is a single-center, randomized, assessor- and statistician-blinded, pragmatic add-on controlled trial. A total of 62 patients with brainstem infarction will be randomly assigned in a 1:1 ratio to a conventional acupuncture group or an adjunctive Shallow Acupuncture group. In keeping with routine inpatient practice in the acupuncture department, both groups will receive standard medical management, routine rehabilitation, and conventional acupuncture, while the adjunctive Shallow Acupuncture group will additionally receive Shallow Acupuncture once daily for 14 consecutive days. The primary clinical outcome will be activities of daily living, assessed by the Barthel Index. Secondary clinical outcomes will include the National Institutes of Health Stroke Scale and the modified Rankin Scale. Exploratory indicators will include measures derived from rs-fMRI and DTI. rs-fMRI analyses will focus primarily on resting-state functional connectivity, whereas DTI analyses will focus primarily on fractional anisotropy; mean diffusivity will be examined as an exploratory diffusion metric. Clinical outcomes will be assessed at baseline, post-treatment, and 1-month follow-up, and neuroimaging assessments will be performed at baseline and post-treatment.

ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (approval numbers: YE2024-202-01 and YE2024-203-01). The findings will be disseminated through peer-reviewed publications and academic conferences.

CLINICAL TRIAL REGISTRATION: https://itmctr.ccebtcm.org.cn/zh/index.html. Identifier, ITMCTR2024000456.

PMID:42500390 | PMC:PMC13395598 | DOI:10.3389/fneur.2026.1849749

Compr Psychoneuroendocrinol. 2026 Jul 16;27:100365. doi: 10.1016/j.cpnec.2026.100365. eCollection 2026 Aug.

ABSTRACT

Menopause is a major psychoneuroendocrine transition which can impact emotional functioning and mental health. Although emotion regulation (ER) is fundamental for mental health, intrinsic neural connectivity supporting ER across the menopausal transition remains unexplored. Addressing this gap, this study provides the first examination of intrinsic effective connectivity within an ER-related network across menopausal stages. Resting-state fMRI data were acquired from 76 healthy premenopausal (n = 32), perimenopausal (n = 19), and postmenopausal (n = 25) women. Effective connectivity within a predefined ER network was examined using spectral dynamic causal modeling. Further, we assessed how intrinsic connectivity predicts self-reported ER ability within each group. While self-reported ER ability did not differ across groups, resting-state effective connectivity within the ER network varied in a stage-specific manner, with the most heterogeneous effects observed between pre- and perimenopause, suggesting a non-monotonic pattern of between-group differences. Perimenopause was characterized by distinct frontal interaction patterns, reflecting a stage-specific redistribution of network organization rather than a gradual intermediate between pre- and postmenopausal connectivity profiles. Differences regarding postmenopause were restricted to greater weighting of temporo-parietal network components. Connectivity-ER ability associations revealed stage-specific predictive profiles, with distributed fronto-temporal connectivity predicting ER ability in premenopause, frontal-restricted connectivity in perimenopause, and a single frontal connection with reversed predictive direction in postmenopause. Our findings demonstrate that comparable levels of trait-based ER ability are associated with divergent intrinsic network configurations rather than a uniform architecture. Identifying perimenopause as distinct stage of intrinsic network organization advances hormone-sensitive models of intrinsic connectivity and provides a framework for understanding how baseline network organization may adapt during psychoneuroendocrine transitions in women.

PMID:42499590 | PMC:PMC13396911 | DOI:10.1016/j.cpnec.2026.100365

Int Psychogeriatr. 2026 Jul 25:100239. doi: 10.1016/j.inpsyc.2026.100239. Online ahead of print.

ABSTRACT

BACKGROUND: Subcortical vascular mild cognitive impairment (svMCI) is an early stage of cognitive decline, frequently accompanied by emotional disturbances like depressive symptoms. While previous studies have explored cognitive and emotional symptoms in svMCI, research on the associated brain functional changes remains limited. Dynamic functional magnetic resonance imaging (fMRI) provides a novel approach to examining temporal variability in brain activity, offering insights into dynamic neural function changes. This study aims to investigate alterations in dynamic fMRI metrics in svMCI patients and analyze their relationships with cognitive function and depressive symptom.

METHODS: This study enrolled 116 patients with svMCI (60 with depressive symptoms (svMCI+D) and 56 without depressive symptoms (svMCI-D)) and 36 healthy controls (HC). All participants underwent resting-state functional magnetic resonance imaging (fMRI). Dynamic amplitude of low-frequency fluctuations (dALFF), dynamic fractional ALFF (dfALFF), and dynamic regional homogeneity (dReHo) were calculated as key indices. Group differences were tested using one-way analysis of covariance (ANCOVA) with age and gender as covariates, followed by post hoc two-sample t-tests for pairwise comparisons. Partial correlation analyses examined associations between dynamic metrics and cognitive performance (MMSE and MoCA) as well as affective symptoms (HAMD and HAMA). Mediation analyses were then conducted to further probe potential pathways linking altered brain dynamics to clinical measures.

RESULTS: Compared with HC, both the svMCI + D and svMCI-D showed significantly reduced dALFF in several regions, including the left lingual gyrus, left superior temporal gyrus, left cuneus, and right paracentral lobule. In addition, the svMCI + D group exhibited increased dALFF in the right hippocampus. The svMCI-D group showed lower dALFF in the left gyrus rectus and left cuneus. For dReHo, the svMCI + D group demonstrated higher values in the right cingulate gyrus and adjacent cortex, along with lower values in the left thalamus and left inferior frontal gyrus. These altered dynamic measures were positively correlated with depressive severity and negatively correlated with cognitive performance.

CONCLUSIONS: The study showed that patients with svMCI, especially those with depressive symptoms, exhibited significant alterations in dynamic fMRI metrics across multiple brain regions. These changes were associated with cognitive performance and depressive symptom severity. Dynamic measures, including dALFF and dReHo, provide neurobiological markers to better characterize cognitive and emotional disturbances in svMCI.

PMID:42498578 | DOI:10.1016/j.inpsyc.2026.100239

J Affect Disord. 2026 Jul 24:122313. doi: 10.1016/j.jad.2026.122313. Online ahead of print.

ABSTRACT

OBJECTIVE: First-episode, drug-naïve (FEDN) patients with major depressive disorder (MDD) frequently exhibit disturbances in stress perception and cognitive function, yet the neural correlates remain unclear. This study investigated associations of altered regional homogeneity (ReHo) in the right precuneus with subjective stress perception in FEDN MDD.

METHODS: We enrolled 139 FEDN patients and 65 healthy controls. Propensity score matching (PSM) balanced age, sex, and head motion, yielding 63 pairs. Resting-state fMRI was acquired and preprocessed; whole-brain ReHo maps were computed. Voxel-wise group comparison with GRF correction identified decreased ReHo in the right precuneus, which was defined as the region of interest. Within patients, partial correlations between right precuneus ReHo and Perceived Stress Scale (PSS) total, helplessness, and self-efficacy scores were examined, controlling for age, sex, mean framewise displacement, HAMD-17, and HAMA.

RESULTS: Compared to controls, FEDN patients showed significantly decreased right precuneus ReHo. In patients, after controlling for age, sex, mean framewise displacement, HAMD-17 score, and HAMA score, right precuneus ReHo was negatively associated with the self-efficacy dimension of the PSS (r = -0.497, p = 0.011). A nominal positive association was also observed between right precuneus ReHo and the PSS total score (r = 0.399, p = 0.048), whereas no significant association was found with helplessness.

CONCLUSION: Altered right precuneus spontaneous activity was associated with perceived stress-related cognitive appraisal, particularly stress-coping self-efficacy, in FEDN patients with MDD after controlling for depressive and anxiety symptom severity. These findings highlight a potential role of the right precuneus in stress-coping self-efficacy in FEDN MDD patients.

PMID:42498121 | DOI:10.1016/j.jad.2026.122313

Neuroscience. 2026 Jul 24:S0306-4522(26)00489-6. doi: 10.1016/j.neuroscience.2026.07.045. Online ahead of print.

ABSTRACT

BACKGROUND: Neurovascular coupling (NVC) impairment contributes to mild cognitive impairment (MCI), but its relationship with NVC in MCI remains unclear.

OBJECTIVE: To explore the associations between CR, NVC, and cognition in MCI patients, and to clarify their potential correlational patterns.

MATERIALS AND METHODS: We enrolled 113 MCI and 83 healthy controls, all undergoing resting-state fMRI and arterial spin labeling to calculate CBF/neural activity ratios (ALFF, fALFF, ReHo, DC) as NVC measures. Cognitive reserve was assessed using the Cognitive Reserve Index Questionnaire.

RESULTS: Compared to HCs, MCI patients showed heterogeneous NVC alterations: whole-brain CBF-ALFF coupling significantly increased, while CBF-fALFF, ReHo, and DC coupling showed non-significant decreasing trends. Regionally, NVC ratios elevated in visual/subcortical areas but reduced in frontal/temporal lobes. CR, especially education, was the strongest cognitive predictor, with antagonistic interactions among reserve dimensions. CBF-fALFF coupling positively correlated with global cognition, whereas CBF-ALFF negatively correlated with memory. NVC ratios in the right lingual gyrus and medial orbital frontal region significantly mediated the reserve-cognition relationship.

CONCLUSION: This cross-sectional study suggests two potential patterns of association linking CR to cognitive performance in MCI: a neural reserve pattern weakly related to NVC, and a neural compensation pathway potentially involving NVC as an correlate. Multidimensional CR assessment and NVC may serve as promising indicators of neural compensation in MCI.

PMID:42498065 | DOI:10.1016/j.neuroscience.2026.07.045

Behav Brain Res. 2026 Jul 24:116397. doi: 10.1016/j.bbr.2026.116397. Online ahead of print.

ABSTRACT

Problematic smartphone use (PSU) has emerged as a significant concern, associated with disruptions in cognitive function, emotional regulation, and neural processing. Previous studies have shown that the global signal (GS) in resting-state functional magnetic resonance imaging (fMRI) influences neuronal activity within the 0.01-0.1Hz frequency range, yet its spatial pattern in PSU remains poorly understood. In this study, we examined frequency-specific alterations in GS topography in 78 participants (41 PSU and 37 nonPSU individuals) across four frequency bands: slow-2 (0.198-0.25Hz), slow-3 (0.073-0.198Hz), slow-4 (0.027-0.073Hz), and slow-5 (0.01-0.027Hz). Significant group differences in GS topography were observed, particularly in the left calcarine region. Additionally, significant interaction effects between group and frequency band were identified in the supplementary motor area (SMA). Correlation analyses revealed associations between GS alterations and clinical measures, including the pop-up notification frequency and smartphone usage frequency, especially in the higher frequency bands (slow-2 and slow-3). These findings suggest that PSU is associated with frequency-dependent alterations in GS topography, as supported by a significant Group × Frequency interaction in the SMA-particularly in regions implicated in cognitive control and visual processing. The observed alterations in GS coherence, particularly the elevated coherence at slow-5 and correlations in higher bands, may reflect neural dysfunctions related to attentional control and self-regulation, which are central to the behavioral manifestations of PSU. These results enhance our understanding of the neural mechanisms underlying PSU and emphasize the importance of considering frequency-specific brain activity in PSU research.

PMID:42497963 | DOI:10.1016/j.bbr.2026.116397

Addict Behav. 2026 Jul 23;183:108802. doi: 10.1016/j.addbeh.2026.108802. Online ahead of print.

ABSTRACT

BACKGROUND: Alcohol use disorder (AUD) is frequently comorbid with sleep disturbances, yet the neural mechanisms through which sleep and AUD jointly shape brain organization remain unclear. Conventional resting-state analyses describe connectivity but not the energetic cost of transitions between large-scale network states.

METHODS: Resting-state fMRI data from 93 individuals with AUD and 91 demographically matched healthy controls (HC) from the Human Connectome Project were analyzed. Sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI). Static inter-network transition energies were computed across eight canonical networks using network control theory. Group × PSQI interactions were tested for directed transitions, with Bonferroni correction. Exploratory ROI analyses examined limbic-to-subcortical ROI pairs.

RESULTS: Individuals with AUD showed greater sleep impairment than HC, particularly in sleep latency, efficiency, and nocturnal disturbances. A significant Group × PSQI interaction was observed for limbic-to-subcortical transition energy (Bonferroni-corrected p = 0.020). In HC, poorer sleep was associated with lower transition energy; this coupling was absent in AUD. Uncorrected effects converged on transitions targeting the subcortical network. Eleven ROI pairs survived correction, linking parahippocampal, amygdalar, and temporal regions to thalamic subnuclei.

CONCLUSION: Comorbid sleep disturbance in AUD may reflect disrupted energetic regulation of limbic-subcortical state transitions. Network control energy provides a mechanistic framework for understanding sleep-brain interactions in addiction.

PMID:42497733 | DOI:10.1016/j.addbeh.2026.108802

J Psychopharmacol. 2026 Jul 24:2698811261464981. doi: 10.1177/02698811261464981. Online ahead of print.

ABSTRACT

Adolescence is a critical neurodevelopmental stage marked by heightened plasticity and vulnerability to environmental influences such as nicotine. Nicotine disrupts neural function via nicotinic acetylcholine receptors, leading to long-term impairments in reward processing, cognition, and emotional regulation. While links between adolescent nicotine exposure and adult psychiatric or cognitive deficits are established, the influence of genetics and sex remains unclear. We examined the long-term effects of adolescent nicotine exposure on adult behavior and neural circuitry in male and female C57BL/6J and DBA/2J mice. Nicotine (24 mg/kg/day) or saline was administered via subcutaneous osmotic minipumps from postnatal day 37 for 12 days. Behavioral assessments 4 weeks later included the elevated plus maze for anxiety-related behavior and the open field test for locomotor activity after acute nicotine (0.81 mg/kg). Resting-state functional magnetic resonance imaging evaluated brain connectivity changes. Nicotine exposure altered both behavior and functional connectivity, depending on strain and sex. Adult female C57BL/6J mice exposed to nicotine during adolescence had lower anxiety-like behavior and higher locomotor activity, along with increased striatal-hippocampal connectivity, suggesting adaptations either directly related to nicotine exposure or compensatory adaptations. In contrast, adult female DBA/2J mice exposed to nicotine during adolescence showed widespread disruptions in cortico-striatal-thalamic, polymodal association, and hippocampal networks critical for cognitive and emotional regulation. Overall, greater effects were seen in female mice. Findings reveal that adolescent nicotine exposure drives enduring, strain- and sex-dependent changes in adult brain connectivity and behavior. Considering genetics and sex is essential for tailoring interventions for nicotine addiction and its neuropsychiatric consequences.

PMID:42495975 | DOI:10.1177/02698811261464981

Front Neurosci. 2026 Jul 9;20:1877959. doi: 10.3389/fnins.2026.1877959. eCollection 2026.

ABSTRACT

OBJECTIVE: To explore abnormal changes in brain entropy (BEN) and resting-state functional connectivity (RSFC) in peritoneal dialysis (PD) patients and their associations with cognitive impairment (CI).

METHODS: Fifty-three PD patients and 49 age-, gender-, and education-matched healthy controls (HCs) were enrolled. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to calculate BEN and RSFC. Neuropsychological assessments and clinical indicator collection were conducted. PD patients were divided into mild cognitive impairment (MCI) and non-cognitive impairment (NCI) groups using Montreal Cognitive Assessment (MoCA) scores. Correlation analyses were performed between BEN/RSFC values and neuropsychological/clinical indicators.

RESULTS: PD patients exhibited significantly poorer performance in multiple cognitive scales than HCs (all p < 0.001). Compared with HCs, PD patients had decreased BEN in the right middle occipital gyrus and left caudate nucleus, and increased BEN in the left middle temporal gyrus and right fusiform gyrus. Reduced RSFC was found between the right middle occipital gyrus and the right fusiform gyrus, right middle frontal gyrus, and right precuneus in PD patients. BEN and RSFC values were correlated with emotional scale scores, cognitive scale subscores, and clinical indicators (e.g., glycosylated hemoglobin, transferrin saturation).

CONCLUSION: Patients with end-stage kidney disease undergoing peritoneal dialysis present abnormal brain entropy and functional connectivity patterns. These alterations are associated with systemic metabolic disorders, long-term dialysis treatment, and cognitive/emotional impairment.

PMID:42495268 | PMC:PMC13391916 | DOI:10.3389/fnins.2026.1877959

J Alzheimers Dis. 2026 Jul 23:13872877261469189. doi: 10.1177/13872877261469189. Online ahead of print.

ABSTRACT

BackgroundThe mechanisms of early brain damage in cerebral amyloid angiopathy (CAA), a highly prevalent comorbid condition in Alzheimer's disease, are not completely understood. While current CAA diagnosis relies on late-stage MRI markers, impaired neurovascular coupling (NVC) has emerged as a promising early marker.ObjectiveTo investigate whether early vascular changes in CAA are associated with functional brain consequences, we examined the association between NVC and various functional connectivity metrics.MethodsWe analyzed MRI data from 93 older adults (71 ± 9 years old). A subgroup meeting Boston criteria v2.0 for possible or probable CAA (n = 46) was analyzed separately to investigate associations in confirmed CAA-related pathology. NVC (time to peak, time to baseline, and BOLD amplitude) was assessed in the occipital cortex using a visual stimulation task. Functional connectivity was assessed at multiple scales using resting-state fMRI, including within ten standard networks, between individual brain regions (edgewise analysis), and across the whole brain (graph theory).ResultsGeneral linear models, adjusted for age, sex, and clinical diagnosis, showed no significant associations between NVC and global connectivity metrics (networks and graph theory). Edgewise analyses revealed limited significant localized functional connections for each NVC measure. Findings were consistent across the total sample and the CAA subgroup.ConclusionsEarly CAA-related pathology is associated with localized rather than global functional connectivity. While large-scale connectivity remains preserved, edgewise analyses indicate subtle localized functional alterations. This suggests that functional connectivity disruption may originate as small-scale deficits that only progress into widespread, global impairment in advanced disease stages.

PMID:42489441 | DOI:10.1177/13872877261469189

Front Pharmacol. 2026 Jul 8;17:1840628. doi: 10.3389/fphar.2026.1840628. eCollection 2026.

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia (BPD) in preterm infants is frequently accompanied by neurodevelopmental impairment, yet the central neuropharmacological actions of dexamethasone (DEX), a commonly used therapy for severe or evolving BPD, remain incompletely understood. In particular, whether DEX exerts timing-dependent neuroprotection in the developing brain and the mechanisms underlying such effects are unclear.

METHODS: We investigated the neuroprotective effects of DEX in a neonatal rat double-hit model combining prenatal maternal lipopolysaccharide exposure with postnatal hyperoxia. A tapered DEX regimen was initiated on postnatal day (P)1, P3, or P8 to evaluate the therapeutic window. Lung pathology, survival, hippocampal injury, microglial reactivity, behavioral outcomes, resting-state functional magnetic resonance imaging (rs-fMRI), targeted metabolomics, and microglia-neuron coculture experiments were used to characterize pharmacological efficacy and mechanism.

RESULTS: Among the tested regimens, DEX initiated at P3 produced the most consistent protective effects, improving alveolar structure, survival, hippocampal pathology, and microglial reactivity. P3-initiated DEX also improved recognition memory, exploratory/anxiety-related behavior, spatial memory retention, and motor coordination, and was associated with partial restoration of hippocampal functional connectivity. At the molecular level, DEX partially restored hippocampal glutamate/GABA balance, reduced Synapsin I phosphorylation, and normalized VGLUT1/VGAT associated synaptic abnormalities. Mechanistically, microglia-derived IL-1β promoted neuronal ERK/Syn1 activation, whereas DEX interrupted this inflammatory signaling axis in a microglia-neuron coculture system. Targeted metabolomics and perturbation experiments further showed that DEX increased Acod1-dependent itaconate reprogramming under inflammatory priming, thereby suppressing microglial IL-1β and downstream neuronal P-Syn1/Syn1 signaling.

CONCLUSION: These findings identify a developmentally sensitive therapeutic window for DEX neuroprotection in neonatal BPD-associated brain injury and suggest that microglial Acod1-itaconate-dependent regulation of IL-1β/ERK/Syn1 signaling contributes to its central protective effects. This study expands the pharmacological interpretation of DEX beyond pulmonary benefit and supports an immunometabolic framework for understanding corticosteroid actions in the developing brain.

PMID:42488574 | PMC:PMC13388472 | DOI:10.3389/fphar.2026.1840628

Hum Brain Mapp. 2026 Aug;47(11):e70615. doi: 10.1002/hbm.70615.

ABSTRACT

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise in enhancing cognitive and emotional functions, yet its neural mechanisms remain unclear largely because existing analytical methods cannot characterize multiscale functional connectivity nor reliably infer causal interactions between brain regions in the presence of hemodynamic delays in fMRI signals. To address these limitations, we propose a Multiscale Spatiotemporal Causal Mapping (MSTCM) algorithm that integrates community-aware multiscale functional connectivity with delay-compensated causal inference. This design enables MSTCM to characterize multiscale connectivity structure and infer directed information flow with enhanced robustness. In evaluations using simulated fMRI data, MSTCM significantly outperformed seven existing causal inference algorithms across multiple evaluation metrics, including precision, sensitivity, Matthews correlation coefficient (MCC), and area under the receiver operating characteristic curve (AUC). Applied to resting-state fMRI across four predefined large-scale cortical networks before and after taVNS, MSTCM revealed that taVNS reduced functional coupling between the left lateral sensorimotor cortex (L-LSMC) and the right intraparietal sulcus (R-IPS), increased global efficiency, enhanced causal integration within the salience network (SN), weakened causal connectivity within the dorsal attention network (DAN), and strengthened information flow from DAN to SN. These findings suggest that taVNS may enhance cognitive flexibility and emotional regulation by shifting information processing from exteroceptive toward interoceptive pathways and improving large-scale network efficiency. Consequently, this study provides not only a novel methodological approach but also new neuroimaging evidence supporting the clinical potential of taVNS.

PMID:42487269 | DOI:10.1002/hbm.70615

BMC Psychiatry. 2026 Jul 22;26(1):559. doi: 10.1186/s12888-026-08409-y.

ABSTRACT

BACKGROUND: The gut microbiota is intricately implicated in the pathogenesis of Major Depressive Disorder (MDD), with the vagus nerve serving as a key regulatory bridge. Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) has emerged as a promising non-invasive therapeutic strategy for MDD by modulating the gut-brain axis, yet the precise brain-gut interaction mechanisms underlying its antidepressant effects remain poorly characterized. This study is a registered clinical trial (ChiCTR2200059591; Registered 4 May 2022; https://www.chictr.org.cn ).

OBJECTIVE/HYPOTHESIS: This study aimed to verify the clinical efficacy of taVNS for MDD and elucidate the underlying brain-gut crosstalk mechanisms, by integrating comprehensive clinical assessments, resting-state functional magnetic resonance imaging (rs-fMRI) neuroimaging data and gut metagenomic profiling.

METHODS: Ninety-five patients diagnosed with MDD were randomly allocated at a 1:1 ratio to either the active taVNS group (auricular concha stimulation) or the sham taVNS group (superior concha of mid-helix stimulation). Eighty patients (40 per group) completed the entire intervention course and were included in the final statistical analysis. All participants underwent 30-minute stimulation twice daily (4/20 Hz, 3-8 mA) for 8 consecutive weeks (5 days per week). Standardized clinical assessments were administered at baseline and post-intervention, including the 17-item Hamilton Depression Rating Scale (HAMD-17), 14-item Hamilton Anxiety Rating Scale (HAMA-14), and Gastrointestinal Symptom Rating Scale (GSRS). Rs-fMRI was performed to quantify core neural activity metrics, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC); fecal samples were collected for high-throughput metagenomic analysis. Spearman correlation analysis and mediation analysis were further conducted to dissect the interactive relationships between brain neural activity and gut microbiota.

RESULTS: The active taVNS group achieved significantly superior clinical efficacy relative to the sham group, with a HAMD-17 response rate of 62.50% and remission rate of 35.00%, versus 30.00% and 2.50% in the sham group (all P < 0.05). Rs-fMRI analyses revealed significant group×time interaction effects on neural activity: decreased ALFF in the right calcarine sulcus; altered fALFF in the right inferior temporal gyrus, left cuneus, right superior frontal gyrus (SFG) and right angular gyrus; reduced ReHo in the right calcarine sulcus and bilateral insula; and increased DC in the right caudate nucleus and left anterior cingulate gyrus. Gut microbiota profiling identified anaerobic butyrate-producing bacteria and Faecalibacterium prausnitzii as potential biomarkers linked to taVNS therapeutic effects. HAMD-17 scores were negatively correlated with Faecalibacterium prausnitzii abundance (r=-0.566, P < 0.01) and positively correlated with anaerobic butyrate-producing bacteria abundance (r = 0.406, P < 0.01). Mediation analysis suggested that fALFF values in the right SFG may indirectly modulate depressive symptoms via regulating Faecalibacterium prausnitzii abundance (indirect effect 95% CI: 0.3039-2.4466), with a significant partial mediation effect observed, though future studies controlling for dietary and other confounding variables are needed to confirm this relationship.

CONCLUSION: taVNS effectively alleviates depressive symptoms in MDD patients via dual complementary pathways: directly modulating neural activity in the right SFG to regulate depression-related brain function, and indirectly maintaining gut microbiota homeostasis by enriching beneficial taxa such as Faecalibacterium prausnitzii. These findings provide novel mechanistic insights into the brain-gut interaction underlying the antidepressant effects of taVNS, laying a theoretical foundation for its clinical application in MDD management.

PMID:42487113 | DOI:10.1186/s12888-026-08409-y

Mol Psychiatry. 2026 Jul 22. doi: 10.1038/s41380-026-03779-x. Online ahead of print.

ABSTRACT

The STRATIFY (Brain Network-Based Stratification of Reinforcement-Related Disorders) and ESTRA (Eating Disorders Stratification) studies were established as harmonised "sibling" cohorts to develop a mechanistically informed framework for stratifying psychiatric disorders. Here, we describe the study design, methodology, and cohort characteristics. Both studies investigate how network properties of brain structure and function, together with biological markers derived from blood-based genomics, epigenetics, and proteomics, relate to reinforcement-related behaviours that cut across major depressive disorder, alcohol use disorder, psychosis, and eating disorders. A further objective is to identify discriminative multimodal features that predict disease onset, symptom course, and functional outcomes, thereby supporting the development of targeted interventions. STRATIFY and ESTRA recruited 674 patients and 70 healthy controls aged 18-30 years (76% females), supplemented by 199 age- and sex-matched healthy controls from the population-based IMAGEN cohort assessed at the same sites using harmonised protocols. Multimodal assessment included structured clinical interviews, self-report measures, cognitive testing, biosamples for molecular analyses, and multimodal MRI (structural, diffusion, resting-state, and task-based fMRI). ESTRA participants additionally completed longitudinal follow-up, and all cohorts were assessed during the COVID-19 pandemic. STRATIFY and ESTRA together constitute a large-scale, open-science resource integrating multimodal brain, behavioural, and biological data across transdiagnostic patient cohorts in early adulthood. The anonymised dataset is available to the research community through managed access, supporting international collaboration and accelerating the development of mechanistically informed classification systems and predictive tools in psychiatry.

PMID:42486943 | DOI:10.1038/s41380-026-03779-x