Most recent paper

Alpha Psychiatry. 2026 Jul 15;27(4):50313. doi: 10.31083/AP50313. eCollection 2026 Aug.

ABSTRACT

BACKGROUND: Adolescent depression necessitates the development of novel therapeutic approaches. Temporal interference stimulation (TIS) is a promising noninvasive neuromodulation technique capable of modulating deep-brain circuits; however, its feasibility in adolescent populations has not yet been established. This open-label pilot study evaluated the feasibility, safety, and tolerability of a five-day TIS protocol targeting the right amygdala in adolescents with depression. Clinical outcomes and neuroimaging findings were assessed as exploratory, hypothesis-generating objectives.

METHODS: Twelve adolescents with depression received five consecutive daily sessions of TIS (2000 Hz carrier frequency with a 100 Hz difference frequency; 20 min/day) targeting the right amygdala. Feasibility was evaluated on the basis of tolerability and adherence rates. Clinical outcomes were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Åsberg Depression Rating Scale (MADRS), 14-item Hamilton Anxiety Rating Scale (HAMA-14), and the THINC-integrated tool (THINC-it) at baseline, post-treatment, and at one-week and four-week follow-up assessments. Exploratory resting-state functional magnetic resonance imaging (fMRI) was performed to investigate neuromodulatory effects.

RESULTS: Nine participants completed the study, corresponding to a completion rate of 75%, with a tolerability rate of 100%. No device-related adverse events were reported. Trends toward improvement were observed in depressive symptoms, anxiety symptoms, and subjective cognitive functioning. From baseline to post-treatment, HAMD-17 and HAMA-14 scores decreased by 52.0% and 56.7%, respectively, and these improvements were maintained at the four-week follow-up, with a 53.3% reduction in depression severity. Exploratory fMRI analyses demonstrated acute increases in functional connectivity between the right amygdala and sensorimotor cortical regions during the first stimulation session.

CONCLUSIONS: A five-day course of right amygdala-targeted TIS was feasible, safe, and well tolerated in adolescents with depression. The observed improvements in depressive and anxiety symptoms, together with acute alterations in amygdala-cortical functional connectivity, provide hypothesis-generating signals that warrant further investigation in rigorously designed sham-controlled trials. However, given the open-label and uncontrolled nature of the study, these improvements cannot be causally attributed to the intervention.

CLINICAL TRIAL REGISTRATION: The study has been registered on https://clinicaltrials.gov/ (registration number: No: NCT06452849; registration link: https://clinicaltrials.gov/study/NCT06452849).

PMID:42694557 | PMC:PMC13539988 | DOI:10.31083/AP50313

Front Endocrinol (Lausanne). 2026 Aug 20;17:1913085. doi: 10.3389/fendo.2026.1913085. eCollection 2026.

ABSTRACT

CONTEXT: Mild autonomous cortisol secretion (MACS) is increasingly recognized as a condition associated with subtle cognitive, functional, and clinical alterations, despite the absence of overt hypercortisolism. Its impact on brain function, sleep quality, and mood, however, remains incompletely understood.

OBJECTIVE: The aim of this observational, cross-sectional study was to investigate cognitive performance, sleep quality, mood, and structural and functional brain alterations in patients with MACS compared with those with non-functioning adrenal tumors (NFAT).

PARTICIPANTS: Forty-eight patients with adrenal incidentalomas were enrolled, including 28 patients with MACS and 20 with NFAT, all without clinical signs of overt hypercortisolism at study entry.

METHODS: Participants had a confirmed failure to suppress cortisol on 1 mg of dexamethasone and underwent comprehensive neuropsychological testing, sleep quality assessment (PSQI), mood evaluation (BDI-II), and brain magnetic resonance imaging (MRI) including structural imaging, voxel-based morphometry, and resting-state functional MRI (fMRI).

RESULTS: Compared with patients with NFAT, those with MACS exhibited slightly lower Mini-Mental State Examination (MMSE) scores and poorer delayed verbal recall, both negatively correlated with serum cortisol levels. Patients with MACS also showed significantly poorer sleep quality, with MACS status and female sex emerging as independent predictors. No group differences were observed in depressive symptoms. Resting-state fMRI revealed altered hippocampal connectivity in MACS, with reduced connectivity with the caudate nucleus and increased connectivity with mesial occipital regions. Voxel-based morphometry showed no structural differences between groups.

CONCLUSIONS: Even mild, clinically silent cortisol excess can be associated with subtle cognitive alterations, impaired sleep, and early functional connectivity changes, despite preserved brain morphology. Longitudinal studies are needed to determine whether these alterations progress over time and whether they improve with targeted treatment.

PMID:42694206 | PMC:PMC13538016 | DOI:10.3389/fendo.2026.1913085

Brain Topogr. 2026 Sep 4;39(6):94. doi: 10.1007/s10548-026-01247-x.

ABSTRACT

The persistent sensitivity to sensory and painful stimuli of people with migraine has been associated with disruption of the salience network (SN). Although migraine is characterized by severe head pain attacks, brain changes have been observed in people with migraine in between attacks (i.e., during the interictal phase). We hypothesized that SN dynamics may be altered in people with migraine during spontaneous attacks as well as an attack imagery task engaging sensory, emotional, and cognitive aspects of pain. To test this, we analysed the SN dynamics in patients with episodic menstrually related migraine without aura across three conditions: at rest during a spontaneous attack; during the interictal phase while performing an imagery task recalling a previous attack and at interictal rest. Healthy controls were studied in matching conditions, including rest and a non-migraine head-pain imagery. We collected functional magnetic resonance imaging (fMRI) data, using a dynamic functional connectivity (dFC) analysis to examine SN temporal features from a total of 26 participants. A significant between-group difference was observed during the pain imagery task, with people with migraine exhibiting a shorter SN dwell time than controls. Such differences were not detected during spontaneous attacks or interictal rest. The between-group difference in SN dynamics observed during the pain imagery condition suggests that this paradigm may be useful for engaging the cognitive and emotional dimensions of pain. However, further work is needed to determine whether this difference is migraine-specific or rather reflects differences in the salience and affective content of the recalled experiences.

PMID:42693231 | DOI:10.1007/s10548-026-01247-x

Seizure. 2026 Aug 25;142:137-145. doi: 10.1016/j.seizure.2026.08.025. Online ahead of print.

ABSTRACT

BACKGROUND: Functional/dissociative seizures (FDS) involve alterations in emotional processing, agency, self-monitoring, and motor control. Post-traumatic stress disorder (PTSD) involves brain systems related to emotional processing, salience detection, memory, and cognitive control. FDS and PTSD converge on several clinical and neurobiological dimensions-including trauma-related vulnerability, emotional processing, dissociation, and alterations involving limbic and regulatory networks-while producing markedly different clinical manifestations. However, it remains unclear which neural abnormalities reflect these shared dimensions and which may be more specifically associated with the emergence of functional seizures.

METHODS: The study included 25 FDS patients, 20 PTSD patients, and 23 healthy controls (HC) who underwent functional and structural 3T MRI. Functional connectivity between 12 predefined brain regions was analyzed using seed-to-voxel analysis. Cluster-based inference and Gaussian random field theory were applied with p-corrected <0.05 and p-uncorrected <0.001 thresholds. Cortical and subcortical structures, including specific hippocampal and amygdala subregions, were segmented using FreeSurfer, and volumes were expressed as mean ± SD.

RESULTS: FDS patients showed lower bilateral dentate gyrus volume (FDS: 142.75 ± 16.28, control: 157.75 ± 17.11, p-adj= 0.019) and greater left anterior cingulate cortical thickness (FDS: 2.85 ± 0.14, control: 2.75 ± 0.17, p-adj= 0.01). Compared with PTSD patients, FDS patients had lower right amygdala central nucleus (FDS: 39.81 ± 5.43, PTSD: 44.15 ± 4.15, p-adj= 0.01) and right pars orbitalis cortical thickness (FDS: 2.62 ± 0.19, PTSD: 2.75 ± 0.17, p-adj= 0.04). Hyperconnectivity was observed from the right hippocampus to the right temporoparietal junction (FDS vs. controls) and from the right insula to the orbitofrontal cortex (FDS vs. PTSD).

CONCLUSION: Anatomical and functional alterations were observed in FDS and PTSD groups versus HC and between FDS and PTSD groups. These findings suggest both shared and disorder-specific brain alterations in FDS and PTSD.

PMID:42691788 | DOI:10.1016/j.seizure.2026.08.025

Dev Cogn Neurosci. 2026 Sep 1;81:101806. doi: 10.1016/j.dcn.2026.101806. Online ahead of print.

ABSTRACT

Entropy is a novel brain measure that holds important information about brain flexibility and functioning, with promise for informing brain development in adolescence, as it has been shown to change across the lifespan. However, little is known about how it changes during the critically important phase of pubertal development, which kickstarts a period of broad neural reorganization and restructuring. This proof-of-concept cross-sectional study examined associations between fMRI signal entropy and early pubertal development in a large, diverse sample of children. Data (N = 6838; 49.6% male; ages 8.92-11.08) was drawn from the first wave of the Adolescent Brain Cognitive Development study. Sample entropy was calculated on the time series of the resting-state fMRI signals for every grayordinate (i.e., cortical vertex and subcortical voxel). Parent-reported pubertal development (approximated Tanner stage) and salivary hormone levels (dehydroepiandrosterone; estradiol; testosterone) were correlated with sample entropy across the whole brain. The patterns of association between sample entropy and pubertal stage/hormone levels were inspected for males and females separately. Findings indicated pubertal development was associated with higher levels of resting state fMRI signal entropy, specifically in the occipital, parietal, and temporal lobes. Associations were apparent in females across most pubertal metrics. For males the constrained range of pubertal development may in part account for weaker associations observed. Further, adjustment for variables associated with early timing of pubertal development (socioeconomic status, body mass index) reduced the strength of puberty-entropy associations for both sexes. Longitudinal research is needed to confirm the associations between sample entropy and puberty, to evaluate whether stronger associations emerge as more males enter puberty in earnest, and to disentangle potential confounds.

PMID:42691580 | DOI:10.1016/j.dcn.2026.101806

Psychiatry Res Neuroimaging. 2026 Aug 22;363:112310. doi: 10.1016/j.pscychresns.2026.112310. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical large-scale brain network organization. Using the comprehensive Autism Brain Imaging Data Exchange (ABIDE-I and ABIDE-II; n = 2013 participants), this study systematically evaluated three representative graph neural network (GNN) architectures for ASD classification based on resting-state functional MRI. The Graph Convolutional Network (GCN), Graph Attention Network (GAT), and Self-Attention Graph Pooling (SAGPool) models were applied to graph representations of functional connectivity among 200 brain regions, following standardized preprocessing and ComBat harmonization. Across 100 repetitions of 10-fold stratified cross-validation, all three models achieved consistent and reproducible accuracy (∼61% balanced accuracy), establishing a robust performance benchmark for connectome-based ASD classification. Permutation-based feature importance analysis revealed convergent brain regions across models, including the bilateral thalamus, right superior temporal gyrus, right middle occipital gyrus, and bilateral precuneus, which are involved in sensory integration, social cognition, and default mode network functioning. These findings indicate that distinct GNN architectures converge on common neurobiological signatures of ASD, highlighting their potential for reliable brain network modeling and biomarker discovery in psychiatry research.

PMID:42691573 | DOI:10.1016/j.pscychresns.2026.112310

Neuroradiology. 2026 Sep 3. doi: 10.1007/s00234-026-04174-7. Online ahead of print.

ABSTRACT

PURPOSE: Presurgical functional mapping is essential for maximizing tumor resection while preserving motor and language function. While task-based fMRI (tb-fMRI) is the current non-invasive standard, its utility is substantially limited in patients with aphasia, paresis, or cognitive impairment who cannot comply with active paradigms. Resting-state fMRI (rs-fMRI) offers a task-free alternative, yet its spatial fidelity and clinical validity compared to task-based methods remain under rigorous evaluation.

METHODS: In this prospective study, we evaluated 12 patients with histologically confirmed brain tumors who underwent rs-fMRI and tb-fMRI for preoperative sensorimotor and language mapping. Motor mapping utilized a bilateral finger tapping block-design paradigm. Language mapping utilized three distinct task paradigms (Silent Word Generation, Rhyming, and Synonym). Spatial concordance was quantified using Dice Similarity Coefficients (DSC), Jaccard Indices, and Receiver Operating Characteristic (ROC) analysis.

RESULTS: rs-fMRI demonstrated fair to moderate spatial concordance with tb-fMRI. For motor mapping, the mean DSC was 0.62 ± 0.08 with high specificity (0.93 ± 0.02). In the language domain, rs-fMRI showed the highest concordance with the Silent Word Generation task (DSC 0.63 ± 0.11). Notably, rs-fMRI exhibited superior signal stability, with significantly fewer motion-censored volumes compared to language task paradigms (p < 0.01). While rs-fMRI demonstrated moderate sensitivity (~ 0.62), it achieved high specificity (0.93-0.94) across all domains however the moderate sensitivity indicates that functionally important regions may remain undetected.

CONCLUSIONS: In this preliminary single-center study, rs-fMRI demonstrates fair to moderate spatial concordance with tb-fMRI and high specificity in delineating core eloquent cortex, though with moderate sensitivity that may leave functionally important regions undetected. The study provides hypothesis-generating evidence supporting the integration of rs-fMRI into multimodal presurgical workflows for neuro-oncology patients who cannot comply with task-based paradigms.

PMID:42690342 | DOI:10.1007/s00234-026-04174-7

Mov Disord. 2026 Sep 3. doi: 10.1002/mds.70510. Online ahead of print.

ABSTRACT

INTRODUCTION: Network attack tolerance (NAT) measures the brain's ability to sustain information flow despite the loss of critical brain regions. In Parkinson's disease (PD), NAT has been linked to cognitive and motor function. However, it remains unclear how dopaminergic degeneration shapes NAT, and whether it relates to motor symptom progression.

OBJECTIVE: To examine dopamine deficiency-related changes in NAT across the early PD disease continuum and its association with longitudinal motor outcomes.

METHODS: We used cross-sectional resting-state functional magnetic resonance imaging of 28 healthy controls, 60 prodromal, and 94 clinical PD patients to create graph-theoretical networks. NAT was assessed at the global and subnetwork levels by calculating the global efficiency upon iterative node removal at different network densities. Using linear mixed-effects models, we assessed how putaminal dopamine transporter (DaT) binding or disease status affected NAT, controlling for network density, age, sex, and education. Baseline somatomotor (SMN) NAT was examined as a predictor of motor symptom progression in 145 patients.

RESULTS: Lower putaminal DaT signal was associated with higher SMN NAT across groups. PD patients exhibited elevated SMN NAT relative to controls. Neither global nor other subnetworks showed effects. While the effect of baseline SMN NAT on motor progression was not significant, an exploratory analysis (Johnson-Neyman) suggested that higher SMN NAT may associate with slower motor decline across most of the observed NAT range.

CONCLUSIONS: Dopaminergic depletion is associated with a targeted SMN reorganization, potentially maintaining network information flow despite progressive hub loss. Whether this reorganization represents compensation or a consequence of progressive pathology requires further longitudinal assessment. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:42689420 | DOI:10.1002/mds.70510

Front Aging Neurosci. 2026 Aug 19;18:1879851. doi: 10.3389/fnagi.2026.1879851. eCollection 2026.

ABSTRACT

INTRODUCTION: This study investigated neurovascular-cerebrospinal fluid dynamic interactions using blood-oxygen-level-dependent-cerebrospinal fluid (BOLD-CSF) coupling metrics and examined their associations with cognitive impairment in patients with MRI-negative unilateral temporal lobe epilepsy (TLE).

METHODS: In this retrospective study, 36 patients with MRI-negative unilateral TLE and 26 healthy controls (HCs) recruited during the same study period were enrolled. Resting-state functional MRI (rs-fMRI) was used to quantify global BOLD-CSF (gBOLD-CSF) and temporal BOLD-CSF (tBOLD-CSF) coupling. Comprehensive neuropsychological assessments included the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Block Design, Phonological Fluency Test (PFT), and semantic verbal fluency (SVF). Partial correlations and multivariable linear regression were performed to evaluate associations between imaging metrics and cognitive performance.

RESULTS: Compared with HCs, TLE patients showed significantly poorer performance on MoCA (p = 0.007), DSST, DST, Block Design, PFT, and SVF (all p < 0.001). Both gBOLD-CSF and tBOLD-CSF coupling strengths were markedly reduced in TLE patients (FDR-p < 0.001 for both). After adjustment for age, sex, education level, and sleep duration, both coupling metrics were positively associated with SVF performance. False discovery rate (FDR) correction was applied to the three prespecified primary imaging-SVF associations-gBOLD-CSF coupling, tBOLD-CSF coupling, and CPV-using the Benjamini-Hochberg procedure. The associations between the BOLD-CSF coupling metrics and SVF performance remained significant after FDR correction (gBOLD-CSF coupling: partial r = 0.723, unadjusted p < 0.001, FDR-adjusted p < 0.001; tBOLD-CSF coupling: partial r = 0.396, unadjusted p = 0.025, FDR-adjusted p = 0.038).

DISCUSSION: Reduced tBOLD-CSF and gBOLD-CSF coupling may serve as functional imaging correlates of semantic network vulnerability in patients with MRI-negative TLE.

PMID:42688357 | PMC:PMC13534037 | DOI:10.3389/fnagi.2026.1879851

Front Neurol. 2026 Aug 19;17:1906087. doi: 10.3389/fneur.2026.1906087. eCollection 2026.

ABSTRACT

BACKGROUND: Cognitive impairment is a common but underrecognized comorbidity in chronic obstructive pulmonary disease (COPD). Lower arterial oxygenation may be associated with altered spontaneous brain activity, but the regional functional correlates linking oxygenation and cognition remain incompletely understood. This study examined amplitude of low-frequency fluctuation (ALFF) abnormalities in COPD patients with cognitive impairment and explored their associations with arterial oxygenation and cognitive performance.

METHODS: This cross-sectional study included 90 participants: 30 healthy controls, 30 COPD patients without cognitive impairment, and 30 COPD patients with cognitive impairment. Cognitive status was assessed using the Montreal Cognitive Assessment (MoCA); one point was added for participants with ≤12 years of education, with the adjusted score capped at 30, and an education-adjusted score <26 was used to define cognitive impairment. All participants underwent arterial blood gas analysis and resting-state functional MRI. Whole-brain voxel-wise ALFF differences were evaluated using analysis of covariance, with an uncorrected voxel-wise cluster-forming threshold of p < 0.001; clusters were considered significant at a cluster-level FDR-corrected threshold of p < 0.05. Adjusted regression, restricted cubic spline, and exploratory cross-sectional mediation analyses were performed in patients with COPD.

RESULTS: COPD patients with cognitive impairment showed lower ALFF in the left precuneus, left putamen, and bilateral parahippocampal gyri, with all clusters surviving cluster-level FDR correction (P_FDR = 0.004-0.021). Higher PaO₂ was associated with higher MoCA total score and higher ALFF in the left precuneus and left putamen after adjustment for multiple comparisons. Higher regional ALFF was also associated with better cognitive performance, with the strongest association observed in the left precuneus. In an exploratory cross-sectional mediation model, left precuneus ALFF statistically accounted for part of the association between PaO₂ and MoCA total score.

CONCLUSION: Reduced left precuneus ALFF may represent a candidate neuroimaging correlate of lower arterial oxygenation and poorer cognitive performance in COPD. Because of the cross-sectional design, the exploratory mediation findings do not establish temporal or causal relationships and require confirmation in larger longitudinal cohorts.

PMID:42688015 | PMC:PMC13533676 | DOI:10.3389/fneur.2026.1906087

Res Sq [Preprint]. 2026 Aug 27:rs.3.rs-10770821. doi: 10.21203/rs.3.rs-10770821/v1.

ABSTRACT

White matter blood-oxygenation-level-dependent (BOLD) signals in resting-state functional magnetic resonance imaging (rs-fMRI) are increasingly recognized for their physiological significance, yet their intrinsic spectral architecture remains largely uncharted. In this work, using high quality data from the Human Connectome Project (HCP), we mathematically model and quantitatively characterize a robustly detectable "second peak" superimposed on the canonical exponentially decaying white matter BOLD spectrum. The spectral signature, with a peak frequency around ~ 0.06 Hz, emerges as a stable individual-level phenotype with broad spatial penetrance across white matter. Cross-tissue analyses reveal that while BOLD signals in cerebrospinal fluid (CSF) exhibit similar low frequency dynamics, white matter provides the most prominent and organized manifestation of this spectral feature. Spatially, the peak follows distinct gradients that mirror macroscopic white matter anatomy. Exploratory analyses in the HCP-Aging cohort further suggest that this band-specific spectral signature undergoes systematic evolution with age. Synthesizing the frequency profile, spatial distribution, and aging trajectory, we propose that the white matter second peak may serve as an organized, tissue-modulated readout of ubiquitous low-frequency physiological dynamics, potentially linked to glymphatic or perivascular clearance mechanisms in the brain. Together, these findings point to a robust spectral phenotype that may open a new noninvasive dimension for investigating white matter functional integrity, brain aging, and relevant physiological mechanisms.

PMID:42687944 | PMC:PMC13533017 | DOI:10.21203/rs.3.rs-10770821/v1

Res Sq [Preprint]. 2026 Aug 25:rs.3.rs-10282950. doi: 10.21203/rs.3.rs-10282950/v1.

ABSTRACT

Amyloid-β and tau, pathological hallmarks of AD, silently accumulate years before clinical symptoms' onset and are associated with neuronal dysfunction and cognitive impairment. Although functional connectivity has shown promise in tracking AD proteinopathy, how large-scale brain functional connections and their temporal variability relate to longitudinal pathological and cognitive changes during the preclinical stage remains unclear. Here, we examined both static and time-varying functional connectivity across brain networks in cognitively unimpaired older adults with a family history of AD, who underwent resting-state fMRI, longitudinal amyloid- and tau-PET imaging, and decade-long neuropsychological assessments. We found that lower static connectivity across multiple large-scale networks was associated with faster longitudinal tau accumulation and, selectively in individuals with elevated amyloid burden, with accelerated cognitive decline. These associations were not observed for time-varying connectivity. Together, our results demonstrate a role of static functional network organization in early pathological and cognitive progression of AD.

PMID:42687915 | PMC:PMC13532734 | DOI:10.21203/rs.3.rs-10282950/v1

Andrology. 2026 Sep 3. doi: 10.1111/andr.70373. Online ahead of print.

ABSTRACT

BACKGROUND: Nonorganic erectile dysfunction (nonorganic ED) is a common subtype of ED characterized by impaired erectile function in the absence of identifiable organic causes. Although ED is increasingly recognized as a multidimensional condition involving interacting biological, psychological, relational, and sociocultural factors, how these influences are integrated within central neural systems in nonorganic ED remains incompletely understood. Objective neurobiological markers are therefore still lacking.

OBJECTIVES: To investigate whether patients with nonorganic ED exhibit abnormalities in local intrinsic brain activity and to examine the association between these alterations and erectile function.

MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging data were acquired from 29 patients with nonorganic ED and 29 age-matched healthy controls. Regional homogeneity (ReHo) was used to assess local synchronization of spontaneous neural activity across the whole brain. Between-group differences were evaluated using voxel-wise analysis. Correlation analyses were performed to assess associations between altered ReHo and erectile function as measured by the International Index of Erectile Function (IIEF).

RESULTS: Compared with healthy controls, patients with nonorganic ED exhibited significantly decreased ReHo in the right anterior insula (family-wise error corrected). Furthermore, reduced ReHo in this region was significantly associated with greater ED severity.

DISCUSSION: These findings indicate that nonorganic ED is associated with disrupted local functional coherence in the anterior insula, a key region involved in integrating interoceptive, emotional, cognitive, and autonomic processes. The observed association with erectile function suggests that impaired integration of these processes may contribute to the central neural mechanisms underlying nonorganic ED.

CONCLUSION: Patients with nonorganic ED exhibit reduced local functional coherence in the anterior insula, which is associated with ED severity. These findings provide preliminary evidence linking central neural dysfunction to clinical symptoms and support the further evaluation of resting-state fMRI metrics as candidate neurobiological markers for nonorganic ED.

PMID:42687555 | DOI:10.1111/andr.70373

CNS Neurosci Ther. 2026 Sep;32(9):e71111. doi: 10.1002/cns.71111.

ABSTRACT

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology.

METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements.

RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting.

CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

PMID:42687126 | DOI:10.1002/cns.71111

Mol Psychiatry. 2026 Sep 2. doi: 10.1038/s41380-026-03839-2. Online ahead of print.

ABSTRACT

Dopaminergic signalling is critical for regulating large-scale brain network dynamics and is implicated in the pathophysiology of psychotic disorders. 22q11.2 deletion syndrome (22q11DS), a high-penetrance genetic risk factor for schizophrenia, is associated with both dopaminergic alterations and disruptions in functional connectivity (FC), yet the degree to which these separate people with 22q11DS from healthy controls and their inter-relationship remains unclear. Eighteen individuals with 22q11DS (no history of psychosis or antipsychotic use) and 22 controls underwent [18F]-DOPA PET imaging to assess striatal dopamine synthesis (indexed by Kicer values) and resting-state fMRI to examine FC. Classification performance using FC, dopamine measures, and their combination was assessed via repeated 10-fold cross-validation. Associations between Kicer, connectivity, and psychotic symptoms were evaluated using linear regression. FC alone classified 22q11DS with 68% balanced accuracy (p = 0.004), Kicer alone with 77% (p < 0.001), and combined measures with 85% balanced accuracy (p < 0.001), indicating additive value. The somatomotor and auditory networks contributed most to group discrimination. Across individuals, higher Kicer was significantly associated with more control-like connectivity profiles (p = 0.011), with significant effects in all striatal subdivisions. No association was found between FC and subclinical psychotic symptoms. This multimodal study demonstrates a significant association between striatal dopamine synthesis capacity and functional brain network architecture in 22q11DS. Higher dopamine synthesis was linked to more normative FC, potentially suggesting FC differences reflect a compensatory, rather than pathogenic role. These findings bridge genetic risk at the 22q11.2 locus with dopamine dysfunction and large-scale networks, offering novel insights into the neurobiology of 22q11DS and related neuropsychiatric risk.

PMID:42686995 | DOI:10.1038/s41380-026-03839-2

Oncologist. 2026 Sep 2:oyag070. doi: 10.1093/oncolo/oyag070. Online ahead of print.

ABSTRACT

BACKGROUND: Life expectancy for cancer patients has improved due to new therapies, but many survivors experience long-lasting side effects, including cancer-related cognitive impairment (CRCI). CRCI symptoms-such as difficulties with attention, memory, processing speed, fatigue, and concentration-can persist for years post-treatment. While clinical evidence of CRCI exists, its underlying mechanisms and neural correlates remain unclear. This study aimed to identify functional brain networks associated with CRCI in breast cancer (BC) patients using structural and functional neuroimaging data.

METHODS: We reviewed studies on CRCI-related brain changes assessed via Diffusion Tensor Imaging (DTI, n = 282), Voxel-Based Morphometry (VBM, n = 177), and functional MRI (fMRI, n = 328). Using the Yeo 7-network resting-state functional atlas, we evaluated the overlap between CRCI-related brain alterations and known functional networks. Overlapping percentages were calculated, and statistical independence tests assessed associations between CRCI and specific networks.

RESULTS: Based on inclusion criteria, six DTI, six VBM, and ten fMRI studies were selected. Chi-square analyses revealed significant associations between CRCI-related changes and several networks: the Dorsal Attention Network (DAN, χ2 = 17.71, p = 0.0001), Default Mode Network (DMN, χ2 = 21.08, p = 0.0000002), Frontoparietal Network (FPN, χ2 = 110.63, p = 0.000002), and Ventral Attention Network (VAN, χ2 = 8.203, p = 0.01).

CONCLUSIONS: Findings highlight network-specific alterations linked to CRCI symptoms in breast cancer survivors. These results enhance understanding of CRCI and may guide targeted therapeutic strategies.

PMID:42684047 | DOI:10.1093/oncolo/oyag070

Front Psychiatry. 2026 Aug 18;17:1892660. doi: 10.3389/fpsyt.2026.1892660. eCollection 2026.

ABSTRACT

OBJECTIVE: To investigate whether structure-informed functional connectivity patterns derived from the Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOL) framework can distinguish children and adolescents with high-functioning autism spectrum disorder (HF-ASD) from typically developing (TD) controls, and to explore the clinical relevance of the identified connectivity features.

METHODS: Multimodal magnetic resonance imaging data, including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI), were acquired from 37 participants with HF-ASD and 33 TD controls. A total of 358 DICCCOL landmarks were localized in each participant's individual brain space based on DTI-derived white matter connectivity patterns. rs-fMRI data were aligned to the corresponding DTI space, and whole-brain functional connectivity was calculated among DICCCOL landmarks. Classification was performed using a linear support vector machine within a fully nested leave-one-out cross-validation framework. All supervised procedures, including FDR-corrected group comparisons, correlation-based feature selection, feature standardization, and hyperparameter optimization, were conducted exclusively within the training data of each cross-validation iteration. Stable discriminative functional connections were further characterized according to their functional network affiliations, and exploratory associations with clinical measures were examined.

RESULTS: The DICCCOL-based functional connectivity model achieved an out-of-fold classification accuracy of 84.29%, with a sensitivity of 83.78%, a specificity of 84.85%, and an area under the receiver operating characteristic curve of 0.832. The stable discriminative functional connections included both increased and decreased connectivity in the HF-ASD group and involved both intra-network and inter-network interactions. These connections were primarily distributed across cognitive-cognitive, cognitive-affective, and affective-affective systems. In addition, several stable functional connections showed significant negative associations with clinical measures, including ADI-R total scores, ADI-R Social Interaction scores, and GEM-PR scores, suggesting potential links between altered connectivity patterns and individual differences in autism-related symptom burden, social functioning, and empathic ability.

CONCLUSIONS: Structure-informed functional connectivity features based on individualized DICCCOL landmarks demonstrated good discriminative potential for identifying HF-ASD in the present sample. The identified connectivity patterns may reflect altered functional integration across cognitive and affective systems and may be related to clinical heterogeneity in ASD. These findings should be considered preliminary, and the identified patterns should be regarded as candidate neuroimaging signatures rather than established diagnostic biomarkers. Validation in larger, longitudinal, independent, and multi-center cohorts is warranted.

PMID:42682665 | PMC:PMC13530007 | DOI:10.3389/fpsyt.2026.1892660

Hum Brain Mapp. 2026 Sep;47(13):e70627. doi: 10.1002/hbm.70627.

ABSTRACT

Brain-age prediction from neuroimaging data provides a proxy of biological aging, yet most models rely on structural magnetic resonance imaging (MRI), a modality that captures macroanatomy but offers limited biological specificity. We tested whether integrating molecular-enriched functional connectivity (FC) from resting-state functional MRI (rs-fMRI) data improves brain-age prediction and biological explainability. We analyzed MRI data of 2120 healthy adults (1243/877 F/M; 18-90 years) from three public datasets. Molecular-enriched connectivity maps were derived with Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) using receptor-density templates for the dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporter systems. Support vector regression models were applied to predict chronological age from molecular-enriched FC, structural morphometry, or both combined. The effect of multi-site variability was mitigated via ComBat harmonization with and without Empirical Bayes pooling. We additionally conducted a common-parcellation analysis to assess the impact of differing parcellations between modalities. Single-transporter molecular-enriched FC explained up to 51% of age variance. The most predictive transporter varied by dataset, with DAT dominating in the harmonized and common-parcellation settings. Combining the three molecular-enriched maps consistently improved prediction over any single map and increased explained variance up to 64%. Structural morphometry remained the strongest single modality overall. In the merged multi-site cohort using a common parcellation, adding transporter-enriched FC to structural features yielded a small but consistent reduction in prediction error (mean absolute error (MAE) from 6.02 to 5.81 years), supporting limited complementarity between the two modalities. Residual-level paired comparisons across repeated cross-validation confirmed that this improvement is statistically reliable but modest in magnitude. In contrast, when different parcellations were applied, incorporating molecular-enriched FC into brain age prediction resulted in a 2% higher MAE compared to structural morphometry alone, suggesting that parcellation mismatch may obscure the functional contributions. In conclusion, molecular-enriched FC is a feasible and biologically informative extension to brain-age modeling; however, its added predictive value over structural morphometry was modest and depended on harmonization and atlas alignment.

PMID:42681925 | DOI:10.1002/hbm.70627

Exp Neurol. 2026 Sep 1:116005. doi: 10.1016/j.expneurol.2026.116005. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI) is a serious health concern in the United States and worldwide. Understanding the mechanisms underlying resting-state functional activity can play an important role in profiling induced disruptions, potentially enabling accurate and timely interventions. Due to its homology to the human brain, the porcine brain is a valuable translational model for investigating focal TBI. In this study, we used the porcine controlled cortical impact TBI model targeting the motor cortex to evaluate dynamic disruptions in functional activity in mild or severe TBI, including hemispheric imbalance, reorganization, and compensation mechanisms, using independent component analysis (ICA). Our whole-brain findings revealed that immediately after TBI, high-level resting-state networks (RSNs), including the executive control (ECN) and cerebellar (CN), showed significantly decreased activity, whereas the sensory motor (SMN) network displayed preserved functional activity. Further hemispheric findings demonstrated a significant decrease in ipsilateral functional activity, whereas contralateral functional activity increased in SMN. Additionally, cortical areas (CoAs) associated with the SMN demonstrated a pronounced hemispheric imbalance at the acute phase. Hemispheric and CoAs analyses revealed a restoration of functional activity over a two-month period. These alterations and lateral imbalance suggest potential lateral reorganization, compensation mechanisms, and temporal recovery processes. These findings are consistent with outcomes previously demonstrated in human TBI patients, further underscoring the importance of the porcine translational model for investigating changes in brain activity or connectivity due to TBI and future novel treatments.

PMID:42679942 | DOI:10.1016/j.expneurol.2026.116005

Neuroscience. 2026 Sep 1:S0306-4522(26)00599-3. doi: 10.1016/j.neuroscience.2026.08.056. Online ahead of print.

ABSTRACT

Intellectual disability (ID) is one of the most serious developmental disorders of children, characterized by significant limitations in intellectual function and adaptive behaviors. However, topological alterations of functional brain networks in children with ID remain unclear. This study combined resting-state functional MRI (rs-fMRI) data and graph theory analysis to quantify the topological properties of functional brain networks in children with ID. Thirty-four children diagnosed with ID and twenty-eight sex-, age-, and education-matched healthy controls (HC) were included. Global, modular and nodal characteristics were calculated to investigate ID-related alterations in functional brain networks. Compared with HCs, decreased clustering coefficient and local efficiency were revealed in children with ID, indicating reduced functional segregation. At the nodal level, children with ID exhibited nodal alterations concentrated in the ventral attention network (VAN), particularly in the left middle cingulate gyrus and bilateral insula, together with nodes in the dorsal attention network (DAN) and the subcortical network (SubN). At an uncorrected threshold, modular connectivity analysis revealed exploratory decreases of subcortical-cortical connectivity between SubN and the somato-motor network (SMN), between the SubN and VAN, between the SubN and frontoparietal network (FPN), and between the SMN and VAN, as well as altered connector and provincial hub indices across the default mode, limbic, frontoparietal, visual and subcortical networks in the ID group. Together, our findings provided preliminary multi-level evidence of functional network reorganization spanning subcortical, sensory, attention, and control systems in children with ID, providing new insights into the topological organization of the cognitive dysfunction in ID.

PMID:42679919 | DOI:10.1016/j.neuroscience.2026.08.056