Most recent paper

Front Neurosci. 2026 Mar 23;20:1787670. doi: 10.3389/fnins.2026.1787670. eCollection 2026.

ABSTRACT

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social communication and restricted, repetitive behaviors. Increasing evidence suggests that neuroinflammatory processes are closely associated with the pathophysiology of ASD, linking immune dysregulation with altered brain development and function. This review synthesizes current findings on the relationships between neuroinflammatory mechanisms, biochemical and metabolic alterations, and functional brain connectivity, as revealed by neuroimaging-particularly functional magnetic resonance imaging (fMRI). Across clinical, postmortem, and imaging studies, individuals with ASD show consistent evidence of microglial and astroglial activation, altered cytokine profiles (including IL-1β, IL-6, and TNF-α), and markers of oxidative stress such as glutathione imbalance and lipid peroxidation. These immune and metabolic alterations are associated with changes in synaptic plasticity, neurotransmission, and large-scale neuronal network organization, including altered functional connectivity within the default mode, salience, and executive control networks. Complementary imaging modalities further support links between glial activity, excitatory-inhibitory imbalance, and aberrant connectivity patterns. Emerging evidence also highlights interactions between inflammation, lipid metabolism, neurotransmitter systems (notably serotonin and dopamine), and genetic and epigenetic factors that modulate immune responses in ASD. Integrating inflammatory and metabolic biomarkers with fMRI and spectroscopic measures provides a promising framework for characterizing biologically informed ASD subtypes and advancing precision diagnostic and therapeutic strategies. Overall, current evidence supports a multilevel neuroimmune framework in which chronic inflammation and oxidative stress are associated with atypical functional brain connectivity in ASD. Future longitudinal and multimodal studies are required to validate candidate biomarkers, clarify mechanistic pathways, and evaluate interventions targeting neuroinflammatory processes.

PMID:41947852 | PMC:PMC13050867 | DOI:10.3389/fnins.2026.1787670

Neural Plast. 2026;2026(1):e9968808. doi: 10.1155/np/9968808.

ABSTRACT

Persistent postural-perceptual dizziness (PPPD) is a disabling functional vestibular disorder characterized by chronic dizziness and visually and motion-induced unsteadiness that markedly impairs daily activities, yet it lacks objective neurobiological markers. We acquired resting-state functional MRI (rs-fMRI) in 52 patients with PPPD and 50 age- and sex-matched healthy controls (HCs) and analyzed the data using a three-tier approach: (i) functional network connectivity (FNC) of independent component analysis (ICA-FNC), (ii) voxel-wise measures of spontaneous amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), and (iii) seed-based connectivity using a priori vestibular and subcortical regions of interest (ROIs; e.g., cerebellar (CB) nodulus, parafascicular thalamus, and caudate). Integrating these analytic tiers, we observed a coherent pattern: broadly increased connectivity of CB and primary visual (VIS) networks together with selective hypoconnectivity between a brainstem-cerebellar (BSC) component and the multimodal vestibular cortex (MVC), oculomotor (frontal eye field [FEF]), and default-mode networks (DMN). Voxel metrics revealed decreased ALFF in parietal and frontal opercular cortices-key vestibular integration regions-contrasting with increased fALFF in mid-cingulate, lateral occipital, and premotor areas. Seed-based mapping identified strengthened thalamo-VIS, striato-limbic, and nodulus-hippocampal connectivity. Importantly, increased BSC-to-VIS coupling correlated positively with depressive symptom severity and state anxiety, but negatively with balance confidence and psychological resilience, linking network imbalance to the biopsychosocial phenotype of PPPD. These findings support a multiscale signature of vestibular cortical disengagement accompanied by maladaptive VIS-CB reinforcement and motivate multicenter validation of network-level markers as adjuncts to symptom-based diagnosis.

PMID:41947631 | DOI:10.1155/np/9968808

Hum Brain Mapp. 2026 Apr 1;47(5):e70526. doi: 10.1002/hbm.70526.

ABSTRACT

Network topology measures characterise brain networks' organisation. Graph theoretical approaches have shown fMRI topology metrics' association with cognitive performance. Because arbitrary connectivity threshold selection biases such metrics, alternatives including the minimum spanning tree (MST) and novel measures following principles of persistent homology were proposed. The present study compared alternative and graph theoretical metrics in association with cognition for resting-state and task-fMRI. Functional connectivity matrices were computed from Human Connectome Project (Young Adult) fMRI scans during resting-state, working memory (WM), gambling, language, motor, relational processing, social cognition, and movie-watching conditions. Global efficiency, clustering coefficient (at three thresholds), diameter, leaf fraction (LF), backbone strength (BS), and cycle strength were measured. Each was tested in association with cognitive test scores. ResultsBS significantly predicted general cognitive performance, specifically progressive matrices score, composite fluid and crystallised cognition, vocabulary, spatial orientation, and WM. Diameter significantly predicted WM. WM task BS outperformed the predictive performance of graph theory measures, but not at rest, where MST LF outperformed other measures. Stronger associations were observed between cognitive test scores and topology measures derived from task-based fMRI, especially the N-Back task, as opposed to resting-state fMRI. Among task-based topology measures, BS was the most strongly related to cognition.

PMID:41947425 | DOI:10.1002/hbm.70526

Brain Imaging Behav. 2026 Apr 7;20(2):71. doi: 10.1007/s11682-026-01135-9.

ABSTRACT

Irritable bowel syndrome (IBS) affects 9.3%–35.5% of the population, with women at greater risk. It is often comorbid with anxiety, depression, and cognitive dysfunction. Understanding the neural mechanisms underlying these comorbidities is crucial for identifying IBS pathology and developing targeted treatments. Functional magnetic resonance imaging (fMRI) offers valuable insights into brain connectivity and psychopathology. This review evaluates research on the link between functional connectivity, mood, and cognition in IBS. We systematically searched Embase, PubMed, and PsycINFO for studies published between 2010 and 2024, identifying 49 studies using both resting-state and task-based fMRI. Of these, 12 studies meeting inclusion criteria were reviewed. Across studies, IBS was associated with altered connectivity in the salience (SN), sensorimotor (SMN), default mode (DMN), and executive control (ECN) networks. Reported cognitive findings largely reflected executive and attentional control processes occurring in the context of pain anticipation, salience detection, and interoceptive awareness rather than domain-general cognitive impairment. Alterations in the SN, particularly involving the pregenual anterior cingulate cortex and anterior midcingulate cortex, were linked to increased visceral sensitivity and affective symptoms. Disrupted DMN connectivity was associated with altered self-referential processing and emotional regulation, while changes in the SMN and ECN suggested differences in sensory integration and top-down control. Notably, several studies showed that group differences in functional connectivity were reduced or no longer significant after accounting for anxiety and depression, suggesting that mood symptoms may play a mediating role in brain network alterations in IBS. While the literature is limited by small samples and sex imbalance, this review highlights a multi-network model of IBS that emphasizes emotional–cognitive–visceral interactions and points to important directions for future longitudinal research.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11682-026-01135-9.

PMID:41945210 | PMC:PMC13056754 | DOI:10.1007/s11682-026-01135-9

PLoS One. 2026 Apr 7;21(4):e0339921. doi: 10.1371/journal.pone.0339921. eCollection 2026.

ABSTRACT

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that is primarily characterized by deficits in social communication and restricted or repetitive behavioral patterns. Although psychologists contribute significantly to the understanding of ASD, offering insights into its cognitive, emotional, and behavioral dimensions through assessments, diagnoses, therapeutic approaches, and family support, the diagnostic process remains complex. This complexity arises from the diverse manifestations of the disorder and the challenges associated with data sharing. In addition, conventional machine learning approaches for ASD detection may struggle with high-dimensional neuroimaging data and may require careful feature engineering. Consequently, this motivated us to enhance ASD diagnosis by incorporating deep learning (DL) techniques for feature extraction alongside a modified exponential-trigonometric optimization (ETO) algorithm as a feature selection (FS) technique. The modified ETO integrates the Arithmetic Optimization Algorithm (AOA) and the Guided Learning Strategy (GLS) to improve diagnostic performance. To evaluate the effectiveness of the proposed model, we utilized resting-state functional MRI (rs-fMRI) data from the Autism Brain Imaging Data Exchange (ABIDE I). Furthermore, the performance of the proposed model was compared with that of established models. The results indicate that the proposed model achieves competitive and, in most cases, superior performance compared with the benchmark methods, demonstrating superior accuracy, sensitivity, and AUC in diagnosing ASD. On average across the three atlas-based feature sets, the proposed model has an accuracy, sensitivity, and AUC of 73%, 78%, and 79%, respectively.

PMID:41945612 | DOI:10.1371/journal.pone.0339921

Dig Liver Dis. 2026 Apr 6:S1590-8658(26)00323-3. doi: 10.1016/j.dld.2026.03.012. Online ahead of print.

ABSTRACT

BACKGROUND: Minimal hepatic encephalopathy (MHE) is a neuropsychiatric syndrome that significantly affects quality of life. It is associated with neural activity changes, reflected by the amplitude of low-frequency fluctuation (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI). Zinc deficiency compromises cognition; however, its relationship with the neural activity changes in MHE remains unclear.

AIMS: To investigate blood zinc variations in MHE and their associations with ALFF.

METHODS: Blood zinc levels were compared in 150 patients with cirrhosis. Among them, 49 underwent rs-fMRI to evaluate associations between zinc levels and ALFF, after adjusting for confounders.

RESULTS: Blood zinc levels were significantly lower in patients with MHE than in those with no hepatic encephalopathy (4.63 vs. 5.06 mg/L; P = 0.022). MHE prevalence was higher in females than in males (35.2% vs. 19.0%; P = 0.025). ALFFs in the bilateral angular gyrus and precuneus were positively correlated with blood zinc levels, whereas those in the bilateral fusiform gyrus were negatively correlated (P < 0.05 and P < 0.05, respectively).

CONCLUSIONS: Low blood zinc levels in patients with MHE are associated with altered neural activity in the bilateral angular gyrus, precuneus, and bilateral fusiform gyrus, representing a neural basis for cognitive impairment in MHE.

PMID:41945038 | DOI:10.1016/j.dld.2026.03.012

Psychol Med. 2026 Apr 7;56:e93. doi: 10.1017/S0033291726103869.

ABSTRACT

BACKGROUND: Working memory (WM) impairment is a core cognitive deficit in schizophrenia, associated with dysfunction of large-scale brain networks, particularly the triple-network system comprising the default mode, frontoparietal, and salience networks. Given the role of environmental risks like childhood trauma (CT) in cognitive deficits, we investigated whether trauma relates to altered triple-network flexibility and WM in schizophrenia.

METHODS: We enrolled 190 patients with schizophrenia (SZ) and 117 healthy controls (HCs). Among them, 162 SZ and 99 HCs underwent n-back task-based functional magnetic resonance imaging. We computed temporal variability (TV) in the triple-network connectivity, defining ΔTV as the change between 0-back and 2-back conditions. Subgroup comparisons of ΔTV were conducted within each group based on trauma status. Associations of ΔTV with WM performance and clinical symptoms were examined in SZ, followed by mediation analyses testing whether ΔTV mediates the relationship between trauma and WM.

RESULTS: Among HCs, individuals with childhood trauma showed reduced ΔTV across triple-network connections, whereas no such differences appeared in SZ. In SZ, greater ΔTV within the frontoparietal network (FPN) was correlated with lower positive symptom severity (r = -0.211, p-fdr = 0.046) and better n-back target accuracy (r = 0.303, p-fdr = 0.002). Furthermore, ΔTV within the FPN partially mediated the association between trauma and n-back accuracy.

CONCLUSIONS: Our findings highlight the central role of FPN flexibility in mediating childhood trauma's effect on working memory in schizophrenia. This outlines a key pathway through which an early environmental risk (trauma) translates into cognitive and clinical manifestations in schizophrenia.

PMID:41943939 | DOI:10.1017/S0033291726103869

Alzheimers Res Ther. 2026 Apr 6. doi: 10.1186/s13195-026-02003-w. Online ahead of print.

NO ABSTRACT

PMID:41943113 | DOI:10.1186/s13195-026-02003-w

Transl Psychiatry. 2026 Apr 6. doi: 10.1038/s41398-026-03985-9. Online ahead of print.

ABSTRACT

Mild cognitive impairment (MCI) is widely recognized as an early stage of dementia. Epidemiological studies suggest that MCI is more prevalent in females than in males. Notably, there are sex differences in MCI-related brain changes. Resting-state functional magnetic resonance imaging (rs-fMRI) offers a valuable method for assessing brain activity during rest. This study aims to explore sex-specific regional brain activity in participants with MCI during resting states. 86 MCI participants (21 males and 65 females) and 107 normal controls (NCs) (38 males and 69 females) were included in the present study. Regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF), and fractional ALFF (fALFF) were used to assess brain activity. MCI females showed increased ReHo values in the right cerebellum inferior compared to NC females and MCI males. However, MCI males exhibited increased ReHo values in the left hippocampus compared to NC males and MCI females. ReHo values in the right cerebellum inferior were associated with visuospatial skills in MCI males, and language function in MCI females. Additionally, ReHo values in the left hippocampus were associated with attention function in MCI females but not in MCI males. In MCI participants, sex moderated the relationship between ReHo values in the right cerebellum inferior and cognitive function (visuospatial skills and language function), as well as the association between ReHo values in the left hippocampus and attention function. In conclusions, this study revealed sex differences in ReHo of right inferior cerebellum and left hippocampus in MCI, and the association between ReHo and cognitive impairment in MCI differs by sex. These sex-specific patterns of regional brain activity can aid in the development of sex-specific precision medicine.

PMID:41942447 | DOI:10.1038/s41398-026-03985-9

Int Neurourol J. 2026 Mar;30(1):63-72. doi: 10.5213/inj.2550210.105. Epub 2026 Mar 31.

ABSTRACT

PURPOSE: Changes in regional brain activity and functional connectivity (FC) in patients with neurogenic detrusor overactivity (NDO) following spinal cord injury (SCI) remain unclear. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate regional brain activity and FC in NDO patients after SCI.

METHODS: Resting-state fMRI scans were obtained from 20 NDO patients after SCI and 20 healthy controls (HCs). Regional brain activity was measured using regional homogeneity (ReHo). Subsequently, a seed-based whole-brain FC analysis was performed using the regions with significantly different ReHo as seeds. Partial correlation analysis was conducted to examine the relationship between FC values and clinical scores in the NDO patients with SCI.

RESULTS: Compared to HC, patients with NDO exhibited significantly decreased ReHo in the right medial frontal gyrus (MFG). Furthermore, compared to HC, NDO patients demonstrated stronger FC between the seed (right MFG) and voxels in the left pyramis, right cerebellum posterior lobe, and left middle temporal gyrus. Weaker FC was observed between the seed (right MFG) and voxels in the right paracentral lobule. Correlation analyses revealed that the Overactive Bladder Symptom Score and urgency urinary incontinence scores were positively correlated with FC values between the right MFG and the left pyramis.

CONCLUSION: SCI-related NDO patients exhibit abnormalities in both regional brain activity and FC, with supraspinal connectivity deviation extent associated with the severity of lower urinary tract symptom. This study contributes to a better understanding of the potential supraspinal neural mechanisms underlying SCI-related NDO.

PMID:41942338 | DOI:10.5213/inj.2550210.105

Andrology. 2026 Apr 6. doi: 10.1111/andr.70233. Online ahead of print.

ABSTRACT

INTRODUCTION: Delayed ejaculation (DE) is a common sexual dysfunction with unclear neurobiological mechanisms. Few studies have explored its neural substrates using functional magnetic resonance imaging (fMRI), especially combining resting-state and task-state paradigms.

METHODS: Forty-two DE patients and 36 healthy controls (HCs) were enrolled. Clinical data (demographics, IIEF-5, GAD-7, PHQ-9, serum testosterone) and fMRI data (resting-state and visual sexual stimulation-induced task-state) were collected. Data were analyzed using regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuations (fALFF), independent component analysis (ICA), and functional connectivity assessments.

RESULTS: Demographically, DE patients and HCs showed no differences in height, weight, or BMI (all p > 0.05), but DE patients had lower serum total testosterone, reduced IIEF-5 scores, and higher GAD-7/PHQ-9 ratings (all p < 0.05), with higher comorbidity of erectile dysfunction, anxiety, and depression. Resting-state fMRI revealed no significant voxel-wise differences in ReHo or fALFF between groups (all p > 0.05). However, during visual sexual stimulation, the two groups exhibited diametrically opposite responses in sensorimotor network regions. For ReHo, the bilateral precentral gyrus, postcentral gyrus, and rolandic operculum exhibited significant inhibition in DE patients (e.g., PoCG.L: T = -6.56) and robust activation in HCs (e.g., PoCG.L: T = 7.57). For fALFF, DE patients showed inhibition in these regions, including the supplementary motor area and the middle cingulate gyrus, whereas HCs activated them; post-correction, DE patients still showed significant inhibition in the left precentral/postcentral gyrus compared with the HC group. (e.g., PoCG.L: T = -4.44). ICA identified the parahippocampal gyrus (PHG) as a dual-functional hub-core node of the default mode network and cross-network connector-with disrupted functional connectivity to supplementary motor area, inferior parietal lobule, and temporal regions in DE patients.

CONCLUSIONS: DE is associated with stimulus-dependent neural dysregulation rather than inherent resting-state abnormalities. Inhibition of the sensorimotor network and PHG-centered connectivity disruption underlie DE's neurobiological basis, providing potential targets for clinical interventions.

PMID:41940829 | DOI:10.1111/andr.70233

Front Neurol. 2026 Mar 19;17:1756996. doi: 10.3389/fneur.2026.1756996. eCollection 2026.

ABSTRACT

BACKGROUND: High myopia (HM) is a common eye disorder which has become a public health problem globally. Previous neuroimaging studies demonstrated that HM is associated with brain structural abnormalities, whereas the spontaneous brain activity changes in HM are not well studied.

METHODS: 30 HM patients and 31 healthy controls were included in this study. The altered spontaneous brain activity in HM patients and their relationships with disease durations were explored, using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI.

RESULTS: Compared with controls, HM patients showed significant increased ALFF in the left insula, hippocampus, increased fALFF in the right hippocampus, calcarine fissure, superior temporal gyrus, lingual gyrus, increased ReHo in the left middle frontal gyrus, calcarine fissure and right cingulate gyrus, and decreased ALFF, fALFF in the left inferior frontal gyrus (opercular part), left inferior parietal lobule respectively. Besides, the mean ALFF value of left hippocampus and the mean ReHo value of left middle frontal gyrus exhibited significantly positive correlations with disease duration, and the mean fALFF value of left inferior parietal lobule showed significantly negative correlations with disease duration.

CONCLUSION: HM patients associated with neural dysfunctions in the vision network, attention network and limbic system, which may implicate the presence of neurobiological changes involving deficits in sensorimotor, vision and limbic system in HM patients, providing early useful diagnostic biomarkers for HM as well.

PMID:41940298 | PMC:PMC13043415 | DOI:10.3389/fneur.2026.1756996

Front Neurol. 2026 Mar 20;17:1758013. doi: 10.3389/fneur.2026.1758013. eCollection 2026.

ABSTRACT

INTRODUCTION: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by involuntary motor and phonic tics, with diagnosis often delayed due to the 1-year symptom duration criterion. This study aimed to explore early neuroimaging biomarkers of TS in young children, by investigating spatiotemporal alterations in dynamic brain network connectivity in 4-6-year-old children with TS.

METHODS: This retrospective case-control study collected resting-state functional magnetic resonance imaging (fMRI) data from 24 children aged 4-6 years, including 12 drug-naive TS patients and 12 matched healthy controls (N group). Group Independent Component Analysis (GICA) and Independent Vector Analysis (IVA) were used to assess group differences in temporal and spatial dynamic functional network connectivity (FNC), respectively. Correlations between these connectivity alterations and Yale Global Tic Severity Scale (YGTSS) scores as well as disease duration were analyzed.

RESULTS: Statistically significant between-group differences were found in temporal dynamic FNC (p < 0.05), with marginal differences observed in spatial dynamic connectivity (p < 0.1), primarily involving the ventral default mode network (VDMN), primary visual network (PVN), and precuneus network (PCN). The N group showed a wider range and higher strength of FNC values, while the TS group exhibited abnormally enhanced connectivity in the insula region, which was positively correlated with disease duration.

DISCUSSION: This study revealed abnormal temporal and spatial dynamic brain network connectivity in young children at the early stage of TS, particularly in insula-related circuits. These findings provide novel insights into the early neuropathological mechanisms of TS and support the potential of dynamic FNC metrics as early imaging biomarkers for TS in young children.

PMID:41940292 | PMC:PMC13046543 | DOI:10.3389/fneur.2026.1758013

Front Neurol. 2026 Mar 20;17:1782025. doi: 10.3389/fneur.2026.1782025. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aimed to investigate white matter microstructural damage, spontaneous brain activity, and functional connectivity alterations in patients with thyroid-associated ophthalmopathy (TAO) and visual impairment using multimodal MRI.

METHODS: Forty-five TAO patients with visual impairment and 32 healthy controls (HCs) underwent diffusion kurtosis imaging (DKI) and resting-state functional MRI (rs-fMRI). Microstructural changes along the visual pathway were quantified using fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD). Regional spontaneous activity was assessed using the amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF), and seed-based functional connectivity (FC) analyses were employed. Group differences were examinded using two-sample t-tests with false discovery rate (FDR) correction (p < 0.05). Correlations between imaging parameters and clinical indicators were further analyzed.

RESULTS: Compared with HCs, the TAO group showed significantly decreased MK, FA, and MD values in the optic radiation, lateral geniculate body, optic tract, and optic nerve, with MK being the most markedly reduced one. Patients also exhibited increased ALFF in the right parahippocampal gyrus and decreased ALFF in the left calcarine fissure, as well as decreased fALFF in the left calcarine fissure and postcentral gyrus. Further analyses revealed decreased FC between the left calcarine fissure and the right lingual gyrus/middle frontal gyrus/bilateral postcentral gyri, and increased FC with the left supplementary motor area/fusiform gyrus. ALFF/fALFF in visual network-related regions correlated with proptosis and extraocular muscle thickening in TAO patients.

CONCLUSION: TAO is associated with white matter microstructural damage, aberrant spontaneous neural activity, and functional reorganization. The combination of DKI and rs-fMRI (ALFF/fALFF, FC) may provide comprehensively insights into central neuropathological mechanisms, providing a basis for early diagnosis and targeted intervention.

PMID:41940287 | PMC:PMC13046559 | DOI:10.3389/fneur.2026.1782025

Brain Commun. 2026 Mar 24;8(2):fcag106. doi: 10.1093/braincomms/fcag106. eCollection 2026.

ABSTRACT

Emerging evidence indicates that stroke may impair glymphatic function by disrupting cerebrospinal fluid clearance. The coupling between global blood-oxygen-level-dependent signals and cerebrospinal fluid flow has been proposed as a non-invasive biomarker of glymphatic activity. However, it remains unclear whether this coupling can be modulated through rehabilitation. This study investigated whether language therapy in patients with post-stroke aphasia enhances global blood-oxygen-level-dependent- cerebrospinal fluid coupling, thereby reflecting potential restoration of fluid-brain interaction. This longitudinal observational study was conducted at a single centre and included 20 patients with post-stroke aphasia and 35 age- and sex-balanced healthy controls. All participants underwent MRI scanning, including resting-state blood-oxygen-level-dependent and structural imaging. Among the post-stroke aphasia group, 14 patients completed both pre- and post-treatment assessments after undergoing a standardized 4-week speech-language therapy programme. The Western Aphasia Battery was used to quantify language deficits and monitor treatment-related changes. Global blood-oxygen-level-dependent-cerebrospinal fluid coupling was quantified using cross-correlation analysis across the whole brain and four predefined language-related resting-state networks. At baseline, patients exhibited significantly reduced global blood-oxygen-level-dependent-cerebrospinal fluid coupling compared to healthy controls (P < 0.05). Following therapy, coupling significantly increased within the language, salience and dorsal attention networks, whereas coupling within the default mode network significantly decreased (all P < 0.05). Notably, increased global blood-oxygen-level-dependent-cerebrospinal fluid coupling in specific networks was significantly correlated with improvements in targeted language functions, such as object naming, responsive naming and auditory word recognition (P < 0.05). These findings suggest that language rehabilitation enhances neurophysiological coupling between brain activity and cerebrospinal fluid flow, potentially reflecting restoration of fluid-brain interaction in post-stroke aphasia.

PMID:41940189 | PMC:PMC13049551 | DOI:10.1093/braincomms/fcag106

Imaging Neurosci (Camb). 2026 Apr 2;4:IMAG.a.1109. doi: 10.1162/IMAG.a.1109. eCollection 2026.

ABSTRACT

Transcranial direct current stimulation (tDCS) is a non-invasive form of neuromodulation. Previous work has shown that tDCS affects functional connectivity, typically assessed by comparing resting-state functional MRI (rs-fMRI) data collected before and after the intervention. This study focuses on the temporal dynamics of functional connectivity during tDCS. Additionally, electric field simulations are incorporated in functional connectivity analyses to gain more insights into the mechanism of action. Forty-seven healthy female volunteers were enrolled in a randomized, sham-controlled, cross-over design in which sham and active tDCS were administered to the left dorsolateral prefrontal cortex for 20 min at 1.5 mA. Functional connectivity analyses were performed on rs-fMRI data collected before, during, and after tDCS, using three seed regions in the brain: one under the anode, one under the cathode, and one at the brain region where the individual tDCS-induced electric field strength was highest. The rs-fMRI data collected during stimulation were divided into three time windows to obtain temporal information on functional connectivity during stimulation. Functional connectivity was assessed at the whole-brain level using seed-to-voxel analyses as well as within predefined resting-state networks. TDCS did not consistently change functional connectivity over time. On the whole-brain level, active tDCS did not affect functional connectivity during stimulation. After active stimulation, only the functional connectivity between the cathode and the postcentral gyrus was increased. At the network level, changes in functional connectivity were observed following both sham and active tDCS, indicating that these effects could not be specifically attributed to active stimulation. Future research should further investigate the relationship between tDCS-induced effects on functional connectivity and their potential links to clinical responses.

PMID:41938662 | PMC:PMC13047502 | DOI:10.1162/IMAG.a.1109

JAACAP Open. 2025 Nov 27;4(2):254-267. doi: 10.1016/j.jaacop.2025.11.008. eCollection 2026 Apr.

ABSTRACT

OBJECTIVE: The pathophysiology of attention-deficit/hyperactivity disorder (ADHD) is complicated by high rates of psychiatric comorbidities; thus, delineating unique vs shared functional brain perturbations is critical in elucidating illness pathophysiology. We investigated resting-state functional magnetic resonance imaging (rsfMRI)-complexity alterations among children with ADHD, oppositional defiant disorder (ODD), and obsessive-compulsive disorder (OCD), respectively, and comorbid ADHD, ODD, and OCD, within the cool and hot executive function (EF) networks.

METHOD: We leveraged baseline data from 9- to 10-year-old children in the Adolescent Brain and Cognitive Development (ABCD) Study. Data for children who singularly met all DSM-5 behavioral criteria for ADHD (n = 61), ODD (n = 38), and OCD (n = 48), respectively, were extracted, alongside data for children with comorbid ADHD, ODD, OCD, and/or other psychiatric diagnoses (n = 833). Data for a control sample of age-, sex-, and developmentally matched children were also extracted (N = 269). Voxel-wise sample entropy (SampEn) was computed using the LOFT Complexity Toolbox. Mean SampEn within all regions of interest (ROIs) of the EF networks was calculated for each participant. Hierarchical models with generalized estimating equations compared SampEn of comorbidity-free and comorbid ADHD, ODD, and OCD within the EF networks.

RESULTS: SampEn was reduced in comorbidity-free ADHD and ODD in overlapping regions of both EF networks compared with the healthy controls, including the bilateral superior frontal gyrus, anterior/posterior cingulate gyrus, and bilateral caudate (Wald statistic = 5.682-10.798, p < .05, and Benjamini-Hochberg [BH] corrected), with ADHD additionally affected in the right inferior/middle frontal gyrus and bilateral frontal orbital cortex (Wald statistic = 7.231-9.420, p < 0.05, and BH corrected). Among comorbid presentations, the presence of ADHD symptomatology was associated with significantly lower SampEn in every ROI (z = -3.973 to -2.235, p < .05, and BH corrected).

CONCLUSION: ADHD and ODD shared common impairments underlying the EF networks in the comorbidity-free presentations, with ADHD showing more widespread complexity reduction. When ADHD co-occurred with other psychiatric disorders, the reduction in SampEn extended beyond the regions affected in comorbidity-free ADHD, indicating that comorbidities amplify neural complexity deficits. In contrast, no significant SampEn alterations were observed in OCD, whether presented alone or in combination with ADHD.

PMID:41938226 | PMC:PMC13043473 | DOI:10.1016/j.jaacop.2025.11.008

J Affect Disord. 2026 Apr 3:121743. doi: 10.1016/j.jad.2026.121743. Online ahead of print.

ABSTRACT

Increasing attention has been paid to the nonlinear functional activity of human brain regions. This paper extends Chatterjee's correlation coefficient (CCC) method to model nonlinear relationships in brain functional networks explicitly. Specifically, the reliability and effectiveness comparisons between CCC and the Pearson correlation coefficient (PCC) are demonstrated using simulated data and two real resting-state functional magnetic resonance imaging (rs-fMRI) datasets: The Midnight Scan Club dataset and the UCLA dataset. The results demonstrate that CCC accounts for both linear and nonlinear dependencies and that its reliability is better than that of PCC. Additionally, from a whole-brain perspective, the number of connections in different brain regions was observed in the following order: bipolar disorder (BP) and healthy controls (HC) > adult attention-deficit/hyperactivity disorder (ADHD) and HC > schizophrenia (SZ) and HC. The commonalities among the three psychiatric disorders compared to HC were differences in occipital, default, cerebellum, and the regions connected to the occipital. Besides, using CCC: occipital performed classification best (AUC: 0.657) between ADHD and HC, and (AUC: 0.622) between BP and HC, but fronto_parietal performed classification best (AUC: 0.700) between SZ and HC. This method enhances sensitivity to group differences and may provide new insights for exploring functional networks based on fMRI in the future.

PMID:41936984 | DOI:10.1016/j.jad.2026.121743

Neurobiol Dis. 2026 Apr 3:107380. doi: 10.1016/j.nbd.2026.107380. Online ahead of print.

ABSTRACT

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy made a breakthrough in treating essential tremor (ET), but with variable tremor responses. This study employed support vector machine regression (SVR) to predict tremor response based on preoperative functional connectivity (FC) patterns.

METHODS: Fifty-six ET patients underwent unilateral MRgFUS thalamotomy and resting-state functional MRI (rs-fMRI). The Clinical Rating Scale for Tremor evaluated 12-month post-treatment responses. Two-sample t-tests identified disease-specific FC differences, which were used in SVR to predict responses. Model performance was evaluated using Pearson's correlation coefficient (r), mean squared error (MSE), and validated via permutation and cross-validation. Longitudinal rs-fMRI in 26 patients examined dynamic changes of the connection with the highest predictive contribution.

RESULTS: Patients demonstrated significant improvement in treated hand tremor at 12-month after thalamotomy (p < 0.001), with a mean improvement of 68%. While baseline tremor severity showed a significant negative correlation with treatment improvement (r = -0.37, p = 0.005), it failed to predict individual outcomes in regression models (linear regression: p = 0.98; SVR: p = 0.46). SVR identified a preoperative FC pattern that predicted tremor response (r = 0.38, p = 0.03; MSE = 0.05, p = 0.02). Longitudinal analysis demonstrated the restoration of the connection with the highest predictive contribution, which increased post-treatment (p = 0.005) and correlated with tremor improvement ratio (r = -0.49, p < 0.001).

CONCLUSION: Preoperative FC patterns predict tremor responses to MRgFUS in ET, serving as a potential imaging biomarker for personalized treatment planning.

PMID:41936873 | DOI:10.1016/j.nbd.2026.107380

J Affect Disord. 2026 Apr 2:121733. doi: 10.1016/j.jad.2026.121733. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the interaction between HPA-axis gene polymorphisms (FKBP5, NR3C1, AVPR1B, SLC1A3, SKA2) and brain functional alterations in adolescent depression.

METHODS: Between May 2021 and June 2024, 150 medication-naïve depressed adolescents and 44 healthy controls underwent HPA-axis SNP genotyping and resting-state fMRI scanning. Logistic regression was performed to evaluate SNP-depression associations, and chi-square tests were used to assess Hardy-Weinberg equilibrium (HWE) and genotype distributions. Imaging metrics (ALFF/fALFF/ReHo/FC) were analyzed via independent t-tests (group differences) and 2 × 2 ANOVA (diagnosis/genotype main effects + interaction) with FDR correction (p < 0.05), followed by depression score correlation analysis.

RESULTS: Among the examined HPA-axis gene polymorphisms, only SKA2-rs7208505 showed a significant association with depression, with G allele carriers exhibiting increased risk (OR = 1.751-2.321, p < 0.05), whereas NR3C1-rs41423247, AVPR1-rs28373064, FKBP5-rs9470080, and SLC1A3-rs2269272 showed no associations (all p > 0.05). Depressed adolescents exhibited elevated ALFF/ReHo in the right precentral gyrus (PreCG) /supplementary motor area (SMA) and increased sensorimotor network connectivity, but decreased ALFF in the cerebellum, angular gyrus, and precuneus (all p < 0.05, FDR-corrected). A Diagnosis×SKA2-rs7208505 interaction significantly modulated functional connectivity from right PreCG to bilateral inferior temporal and postcentral gyri (all p < 0.05, Bonferroni-corrected).

CONCLUSION: SKA2-rs7208505 was associated with adolescent depression, with the G allele conferring risk. A significant Diagnosis×SNP interaction was found for functional connectivity between the right PreCG and bilateral inferior temporal/postcentral gyri, indicating this SNP and brain functional alterations are linked to adolescent depression pathogenesis. These findings provide novel insights and support for early prevention and intervention strategies.

PMID:41935751 | DOI:10.1016/j.jad.2026.121733