Most recent paper
Altered Habenula Resting-State Functional Connectivity and Spatial Associations with Neurotransmitter Receptor Distribution of Major Depressive Disorder with and without Anhedonia
Neuropsychiatr Dis Treat. 2026 Mar 27;22:577735. doi: 10.2147/NDT.S577735. eCollection 2026.
ABSTRACT
OBJECTIVE: This study aimed to examine functional connectivity (FC) alterations in patients with major depressive disorder (MDD), specifically comparing those with and without anhedonia.
METHODS: 24 MDD patients with anhedonia (MDD-WA), 17 MDD patients without anhedonia (MDD-WoA), and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Intrinsic brain function was assessed using resting-state FC and spatial associations with neurotransmitter receptor distribution analyses. The habenula (Hb) was selected as the region of interest (ROI), and the whole-brain FC of the Hb was compared across groups. Spatial correlations between inter-group FC differences and whole-brain neurotransmitter receptor/transporter expression templates, derived using the JuSpace tool, were analyzed. Additionally, FC values from differential brain regions were extracted and correlated with the scores on the clinical scale.
RESULTS: Compared to MDD-WoA patients, MDD-WA patients exhibited reduced FC between the Hb and the left middle frontal gyrus (MFG). Enhanced FC was observed between the Hb and bilateral putamen in MDD-WA patients compared to HCs. Additionally, in the MDD-WA group, changes in the Hb whole-brain FC demonstrated positive correlations with the spatial density distribution of specific neurotransmitter receptors and transporters. In contrast, MDD-WoA showed no significant Hb FC differences or neurotransmitter correlations compared to HCs. No significant correlations were found between the FC values of the intergroup-different brain regions and the total SHAPS-C, total HAMD-17, and all HAMD-17 factor scores (anxiety/somatization, weight loss, cognitive disturbance, retardation, and sleep disturbance).
CONCLUSION: In patients with MDD-WA, FC between the habenula and bilateral putamen, as well as between the habenula and left MFG, was altered. Given that the putamen is a core component of the striatum, all these findings suggest that habenula-prefrontal-striatal dysconnectivity may represent an anhedonia-specific biomarker in MDD. The FC patterns between the habenula and bilateral putamen/left middle frontal gyrus, along with the related neurotransmitter profiles identified in this study, may serve as objective indicators for monitoring therapeutic efficacy in the future.
PMID:41923921 | PMC:PMC13037516 | DOI:10.2147/NDT.S577735
Resting-state fMRI using hidden Markov models reveals abnormal dynamic brain functional states in asthma
Sci Rep. 2026 Apr 1. doi: 10.1038/s41598-026-44794-w. Online ahead of print.
ABSTRACT
Asthma involves not only airway inflammation but also aberrant central nervous system regulation. While static functional connectivity studies have revealed brain network abnormalities in asthma patients, the transient temporal dynamics of brain functional states remain largely unexplored. To investigate brain dynamic functional connectivity characteristics in asthma patients using Hidden Markov Models (HMM) and to identify potential neurobiological markers associated with clinical symptoms. Resting-state fMRI data were acquired from an initial pool of participants, with 120 age- and gender-matched individuals (60 asthma patients and 60 healthy controls) included after stringent quality control and head-motion scrubbing. HMM was applied to identify recurring brain states based on the Schaefer-142 parcellation. We compared groups on fractional occupancy (FO), mean dwell time (MDT), and transition probabilities. Exploratory correlation analyses were performed to evaluate the relationship between HMM-derived metrics and clinical scores (ACT and pulmonary function). HMM identified nine distinct functional states. Asthma patients exhibited a significantly increased MDT and FO in State 2 (characterized by somatomotor and dorsal attention network involvement) compared to healthy controls (p < 0.05). Exploratory analysis revealed a nominal positive correlation between the MDT of State 2 and Asthma Control Test (ACT) scores (r = 0.30, p < 0.05, uncorrected), suggesting a potential compensatory role of this state in symptom monitoring. Our findings reveal altered brain state dynamics in asthma, particularly the prolonged occupancy in a sensory-attention-related state. While the brain-clinical associations are exploratory, these dynamic metrics provide novel insights into the central mechanisms of asthma and may serve as preliminary neurobiological markers for symptom control.
PMID:41922478 | DOI:10.1038/s41598-026-44794-w
Functional brain connectivity in type 1 diabetes and associations to diabetes complications - a systematic review of fMRI studies
Front Neuroendocrinol. 2026 Mar 30:101249. doi: 10.1016/j.yfrne.2026.101249. Online ahead of print.
ABSTRACT
A systematic review was conducted to investigate functional brain changes in type 1 diabetes mellitus (T1DM) assessed with functional magnetic resonance imaging (fMRI) between 2006 and 2025. A total of 27 eligible studies were included, involving 1072 participants with T1DM, with a mean age ranging from 20.4 to 51.5 years. The quality of these studies was evaluated using the NIH Quality Assessment Tool. Resting-state fMRI (n = 12) demonstrated 1) altered brain networks, especially in the default mode and salience networks, and 2) changes in subcortical regions and the frontal lobe. Task-based fMRI (n = 15) showed increased activity in the visual, salience, and thalamic networks, and decreased activity in the default mode network. The review highlights the complex relationship between T1DM and brain changes, presenting evidence of deviations from normal brain activity in specific areas involved in sensory-motor, limbic and cognitive regions that may reflect neurophysiological adaptations or consequences related to T1DM. Registration: PROSPERO (International Prospective Register of Systematic Reviews) under ID: CRD42023456789.
PMID:41921840 | DOI:10.1016/j.yfrne.2026.101249
Altered functional connectivity is associated with Repeatable Battery for the Assessment of Neuropsychological Status across the dementia spectrum
J Int Neuropsychol Soc. 2026 Apr 1:1-12. doi: 10.1017/S135561772610191X. Online ahead of print.
ABSTRACT
OBJECTIVE: The quest for non-invasive and cost-effective biomarkers for mild cognitive impairment (MCI) and Alzheimer's disease (AD) has led to growing interest in resting-state functional magnetic resonance imaging (MRI). This study examined associations between whole-brain functional connectivity measures and cognitive performance across a spectrum of cognitive aging.
METHOD: A total of 108 older adults (mean age 74.1 ± 5.7 years), comprised of cognitively intact individuals, participants with amnestic MCI, and those with mild dementia due to probable AD, underwent high-resolution structural MRI and resting-state functional MRI scans and cognitive testing with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Functional connectivity values were derived from a 17-network brain parcellation. Correlations were established between network connectivity values and RBANS Index scores.
RESULTS: Analyses revealed that lower RBANS Attention Index and Total Scale scores were significantly associated with increased connectivity between the ventral attention, central executive network, and limbic and default mode networks. Lower RBANS total scores were also associated with functional connectivity strength between the dorsal default mode networks and lateral frontoparietal regions of the central executive network, with increased connectivity observed across the dementia spectrum (Intact-MCI-AD).
CONCLUSIONS: These findings suggest that aberrant and potentially compensatory increases in functional connectivity may be linked to cognitive decline, supporting the utility of resting-state functional MRI as a promising biomarker for MCI and AD.
PMID:41919533 | DOI:10.1017/S135561772610191X
Resting state functional connectivity in pedophilic disorder and degarelix treatment
Acta Neuropsychiatr. 2026 Apr 1:1-20. doi: 10.1017/neu.2026.10073. Online ahead of print.
ABSTRACT
OBJECTIVE: There is a need for deeper understanding of neurological and psychological aspects of pedophilic disorder (PeD) to improve management of the disorder and thereby prevent child sexual abuse. Functional magnetic resonance imaging (fMRI) measures have been suggested as imaging biomarkers that may contribute towards this goal. A previous study using degarelix, a testosterone suppressing drug, showed promising results in decreasing the risk of committing child sexual abuse among individuals with PeD. In this study, we evaluate functional connectivity (FC) related to PeD and degarelix treatment.
METHODS: We used independent component analysis on resting state (rs)fMRI data acquired at baseline as well as two and ten weeks after injection of degarelix (or placebo) to evaluate FC alterations related to PeD and the degarelix treatment effect.
RESULTS: FC was altered in relation to several resting state networks in individuals with PeD compared to healthy controls at baseline. At follow-up time points, however, group comparisons were inconclusive and did after FDR correction not render statistically significant FC alterations when comparing patients to controls or related to degarelix treatment, child sexual abuse (CSA) dynamic risk scores or comorbidities.
CONCLUSION: We found FC alterations in PeD compared to healthy controls at baseline, however, no consistent, treatment specific FC signature of degarelix was demonstrated.
PMID:41918172 | DOI:10.1017/neu.2026.10073
Brain Functional Connectivity as a Mediator Between Hematological Metrics and Cognitive Decline in Children With Beta-thalassemia Major
Brain Behav. 2026 Apr;16(4):e71363. doi: 10.1002/brb3.71363.
ABSTRACT
PURPOSE: This study aimed to identify functional brain connectivity patterns associated with cognitive performance in Beta-thalassemia major (β-TM) children and to determine whether hematological factors influence cognition indirectly through alterations in connectivity.
METHOD: We recruited 25 children with β-TM and 35 age-matched healthy controls. Cognitive performance was assessed using the Wechsler Intelligence Scale (WIS). Resting-state functional MRI data were processed to construct whole-brain functional connectivity matrices. We applied network-based statistics (NBS) to compare connectivity differences between groups and connectome-based predictive modeling (CPM) with cross-validation to predict cognitive scores. Mediation analyses were further conducted to test whether hematological metrics (hemoglobin level, red blood cell distribution width) impacted cognition through functional connectivity.
FINDING: Compared to controls, β-TM children showed significantly reduced WIS scores and widespread disruptions in functional connectivity, particularly in cerebellar, motor, and temporal networks. The CPM approach identified a predictive network that largely overlapped with the NBS-derived network and robustly predicted WIS scores. Mediation analysis revealed that hemoglobin and red blood cell distribution width influenced cognitive scores indirectly through altered connectivity, indicating a full mediation effect.
CONCLUSION: This study provides evidence that hematological abnormalities in β-TM children impair cognitive performance via their impact on functional brain networks. Functional connectivity signatures derived from CPM may serve as early neuromarkers of cognitive vulnerability and could inform future monitoring and intervention strategies in this population.
PMID:41917757 | DOI:10.1002/brb3.71363
Dynamic functional connectivity is related to cognitive performance of prodromal Lewy body dementia
J Neural Transm (Vienna). 2026 Mar 31. doi: 10.1007/s00702-026-03148-6. Online ahead of print.
ABSTRACT
Brain connectivity dynamics in mild cognitive impairment with Lewy bodies (MCI-LB) is largely unknown. We aimed to identify brain connectivity dynamics related to cognitive performance in drug naïve MCI-LB. Healthy (55 participants, age 67.7 ± 6.4, 33 females) and MCI-LB subjects (30 participants, age 68.5 ± 6.0, 16 females) underwent cognitive testing and fMRI. The fast eigenvector centrality dynamic functional connectivity was employed to detect connectivity states. Mean state duration and occurrence were correlated to cognitive measures. In the MCI-LB group only, the occurrence and mean duration of the state characterized by between-network connectivity of the dorsal attention, sensorimotor, and visual networks correlated with visuospatial function (VSF) domain z-scores (r = 0.68, p = 0.003, and r = -0.68, p = 0.003, respectively). The VSF also correlated with the occurrence of the state characterized by intra-network connectivity of the frontoparietal control network (r = -0.55, p = 0.041). We identified specific mechanisms that seem to facilitate visuospatial performance in MCI-LB.
PMID:41915163 | DOI:10.1007/s00702-026-03148-6
Dynamic Brain State Alterations in Narcolepsy: A Hidden Markov Model Approach to Thalamocortical Instability and Symptom-Specific Neural Correlates
Brain Behav. 2026 Apr;16(4):e71338. doi: 10.1002/brb3.71338.
ABSTRACT
BACKGROUND: Narcolepsy Type 1 (NT1) results from loss of hypothalamic orexin neurons, leading to unstable sleep-wake transitions. However, how this manifests as dynamic whole-brain functional state instability remains poorly characterized.
METHODS: We applied Hidden Markov Modeling (HMM) to resting-state functional magnetic resonance imaging (fMRI) data from 30 patients with NT1 and 30 age- and sex-matched healthy controls to identify recurrent brain states, quantify their fractional occupancy (FO), and examine associations with clinical symptoms-specifically excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) and hallucinations.
RESULTS: Five distinct dynamic brain states were identified. Compared to controls, NT1 patients showed significantly reduced FO in State 1 (thalamocortical arousal/sensory gating; pFDR < 0.001) and elevated FO in State 4 (basal ganglia-limbic-sensorimotor integration; pFDR < 0.001) and State 5 (reward-introspection; pFDR = 0.036). Notably, within the NT1 group, patients with hallucinations exhibited higher FO in State 1 than those without (pFDR = 0.042), suggesting aberrant recruitment of this state during sleep-wake transitions. Additionally, State 4 FO showed a moderate positive correlation with ESS scores (Spearman's ρ = 0.38, pFDR = 0.078).
CONCLUSIONS: NT1 is associated with reduced stability of a thalamocortical alertness state and increased expression of REM-like limbic-subcortical network configurations. State 1 occupancy is relatively elevated in patients with hallucinations, while State 4 shows a positive association with excessive daytime sleepiness and features of REM dissociation. These findings support a dynamic, whole-brain systems-level framework for understanding symptom heterogeneity in NT1.
PMID:41914370 | DOI:10.1002/brb3.71338
Disrupted Emergent Properties of the Brain in Schizophrenia: Insight From Integrated Information Decomposition of Resting State fMRI
Brain Behav. 2026 Apr;16(4):e71352. doi: 10.1002/brb3.71352.
ABSTRACT
BACKGROUND: Schizophrenia is a severe psychiatric disorder marked by specific cognitive and clinical disturbances, for which neuroimaging biomarkers remain elusive. Novel theoretical and computational frameworks, such as integrated information decomposition, offer promising approaches to provide interpretable biomarkers for neuroimaging alterations in schizophrenia, potentially capturing disruptions relevant to consciousness and self-experience.
METHODS: In this preliminary methodological exploration study, resting-state functional MRI (rsFMRI) data from 72 patients with schizophrenia and 74 healthy controls were retrieved and analyzed. Integrated information decomposition was leveraged to assess pairwise brain connectivity according to redundant, transferred, and synergistic components of information processing, as well as an overall metric of emergent consciousness/information integration: Φ. Clinical correlates with the Positive and Negative Syndrome Scale and the Wechsler Adult Intelligence Scale were assessed by partial Spearman correlations. Diagnostic accuracy was assessed through L1-regularized logistic regressions, after 5-fold cross-validation.
RESULTS: Redundancy was positively correlated with intelligence quotient (IQ) across both groups (rho = 0.187, p-value = 0.033). Within patients, information metrics were positively correlated with stereotyped thinking (min rho = 0.343, max p-value = 0.006) and preoccupation (min rho = 0.250, max p-value = 0.046). Positive symptoms were positively correlated with redundancy (min rho = 0.250, max p-value = 0.047). Promising diagnostic accuracy was reached with Φ (balanced accuracy = 64.38%, area under the curve = 70.89%), redundancy (balanced accuracy = 84.93%, area under the curve = 92.30%), and synergy (balanced accuracy = 65.75%, area under the curve = 70.93%).
CONCLUSIONS: These preliminary findings suggest that information metrics may offer clinically relevant, interpretable biomarkers for schizophrenia.
PMID:41913713 | DOI:10.1002/brb3.71352
Neural Correlates of Rumination in Psychiatric Disorders: A Systematic Review of fMRI Evidence
Behav Brain Res. 2026 Mar 28:116181. doi: 10.1016/j.bbr.2026.116181. Online ahead of print.
ABSTRACT
BACKGROUND: Rumination is a transdiagnostic, persistent factor across many psychiatric conditions. Mapping its neural mechanisms may help differentiate ruminative profiles.
OBJECTIVE: To systematically review fMRI studies that evaluated rumination in psychiatric populations METHODS: We searched four databases (PubMed, EMBASE, Web of Science, Scopus) and included studies that integrated rumination measures with fMRI data.
RESULTS: Thirty-two articles met criteria; most were non-randomized (n = 31, 97%) and focused on depression (n = 24, 75%). Across disorders, clinical groups showed higher rumination than healthy controls, including in euthymic participants. In major depressive disorder, neural alterations implicated the default mode network, limbic and striatal regions, dorsolateral prefrontal cortex, and anterior cingulate cortex consistent with maladaptive ongoing processing. Neural signatures often persisted in remitted patients, suggesting possible trait markers of vulnerability. Intervention studies (n = 7) support using neuroimaging to track ruminative profiles and to inform more personalized interventions.
CONCLUSION: This review highlights the importance of examining rumination, here measured via trait questionnaires, state-induction paradigms, cognitive tasks, or resting-state fMRI, using more consistent conceptual and methodological approaches. Although rumination is transdiagnostic, implicated brain regions and networks may show disorder-specific patterns. Given heterogeneity in the literature, future work should prioritize controlled and interventional studies to clarify neural mechanisms and guide circuit-based, targeted treatments. PROSPERO REGISTRATION: #CRD532512.
PMID:41912094 | DOI:10.1016/j.bbr.2026.116181
Disrupted Modular Integration of the Reward System Is Associated With Social Deficits in Autism Spectrum Disorder
Autism Res. 2026 Mar 30:e70241. doi: 10.1002/aur.70241. Online ahead of print.
ABSTRACT
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with atypical social communication as a core symptom. Variations in social information processing in individuals with ASD are associated with the social brain, which encompasses four specific subnetworks, that is, reward system, theory of mind network, mirror neuron system, and face perception network. However, the relationship between neural mechanisms of altered social functioning and modular integration of these subnetworks within the social brain remains unclear in ASD. With resting-state functional MRI (rs-fMRI) data from two large-scale datasets (ABIDE I and II), we computed the participation coefficient to explore the abnormal modular integration of the four subnetworks in 298 ASDs and 348 typically developing (TD) controls. Then, its associations with clinical symptoms, neurotransmitter systems, and transcriptional signatures were investigated. Additionally, the age effect on aberrant modular integration was estimated with linear regression models. Finally, we assessed the reproducibility of our results from a meta-perspective using other datasets. ASD participants exhibited increased integration of the reward system relative to TDs, which was correlated with Social Responsiveness Scale total score, the neurotransmitters such as 5HT1a and GABAa, and the disruption of the transcriptional signatures including cell proliferation and migration as well as tube and tissue morphogenesis. Additionally, the modular integration abnormality of the reward system was stable across development and replicated across datasets. We revealed a symptom-related, neurotransmitter- and transcriptional signature-associated, age-stable, and reproducible modular integration abnormality of the reward system in ASD. This hyper-integration was linked to reduced GABAa and serotonin receptor densities, providing neuroimaging and molecular evidence supporting the excitatory-inhibitory imbalance theory of ASD and insights into the mechanisms underlying social variations in ASD.
PMID:41912444 | DOI:10.1002/aur.70241
Edge-centric functional network analyses and their associated genetic mechanisms in patients with first-episode schizophrenia
Behav Brain Res. 2026 Mar 28:116184. doi: 10.1016/j.bbr.2026.116184. Online ahead of print.
ABSTRACT
Extensive evidence has highlighted disrupted brain connectivity in schizophrenia, yet traditional node-centric approaches have provided only limited insights into its underlying neurobiology. To address this gap, we analyzed resting-state fMRI data from 52 first-episode schizophrenia patients and 51 matched healthy controls, applying an edge-centric framework to compute normalized entropy, which quantifies the diversity of edge community affiliations at each node. Compared with healthy control, patients with schizophrenia exhibited significantly reduced entropy in prefrontal and temporal regions, reflecting diminished network diversity. These alterations were further associated with transcriptomic profiles, with the most relevant genes enriched for synaptic signaling and neurodevelopmental processes. This study demonstrates aberrant edge-centric network dynamics in schizophrenia and their relations to schizophrenia-related molecular pathways, providing novel insights into the pathophysiology of the disorder.
PMID:41912092 | DOI:10.1016/j.bbr.2026.116184
Expansion of attentional scope modulates postural control, motor strategies, and attentional network connectivity in healthy adults: a proof-of-concept mixed-methods study
Front Rehabil Sci. 2026 Mar 12;7:1758682. doi: 10.3389/fresc.2026.1758682. eCollection 2026.
ABSTRACT
INTRODUCTION: Plantar sensory input plays a key role in postural control. However, training protocols that solely amplify this bottom-up input have demonstrated inconsistent efficacy. We hypothesized that a top-down protocol using plantar sensations as a perceptual anchor and expanding the attentional scope from localized plantar sensations to a whole-body reference frame would yield greater improvements than sensory discrimination alone.
METHODS: Forty-eight healthy adults (N = 48) participated in a single 10-minute session of either Sensory Discrimination Only (SDO) or Sensory Discrimination with Expansion of Attentional Scope (SDE). The SDE protocol employs a brief therapeutic dialogue to facilitate this expansion. The Index of Postural Stability (IPS) was assessed at baseline (T0), immediately after the training (T1), and 30 min after (T2). Semi-structured interviews at T0/T1 were text-mined to quantify motor strategies. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected at T0/T1 for region-of-interest (ROI)-to-ROI connectivity analyses, focusing on major large-scale brain networks.
RESULTS: The SDE group demonstrated a significant IPS improvement (ΔIPS ≈ + 0.09, dz = 0.42) and maintained this improvement at 30 min (T0 vs. T2: dz = 0.32), whereas the SDO group demonstrated no change. Qualitative analyses of self-reported motor strategies in the SDE group indicated attentional expansion beyond a plantar perceptual anchor toward whole-body alignment, reflected by increased references to the shoulders while foot-related references remained common. In rs-fMRI, a cluster within attentional circuitry, including the salience and ventral attention networks, demonstrated a significant group × time interaction [threshold-free cluster enhancement [TFCE]/family-wise error [FWE]-corrected p < .05], characterized by reduced connectivity following SDE and a trend toward increased connectivity following SDO.
CONCLUSIONS: In this proof-of-concept study, expanding attentional scope from a plantar perceptual anchor toward a whole-body reference frame was associated with immediate, group-level changes across measures. Postural stability improved, alongside changes in self-reported motor strategies and resting-state connectivity within attentional circuitry. Enhancing sensitivity to bottom-up plantar input remains fundamental; however, these findings suggest a potential next step-learning how to interpret and use plantar input as a whole-body reference signal for balance regulation. Confirmation in randomized and longitudinal studies, including evaluation in clinical populations, is warranted.
PMID:41908177 | PMC:PMC13018112 | DOI:10.3389/fresc.2026.1758682
Cross entropy gradient analysis for Alzheimer's disease assessment
J Alzheimers Dis. 2026 Mar 30:13872877261431317. doi: 10.1177/13872877261431317. Online ahead of print.
ABSTRACT
BackgroundAlzheimer's disease (AD) involves progressive cognitive decline associated with disrupted coordination and information exchange across brain regions. Cross-entropy can characterize inter-regional information flow, but its role in AD remains unexplored.ObjectiveTo evaluate cross-regional brain entropy (CRBEN) derived from resting-state fMRI in normal controls (NC), mild cognitive impairment (MCI), and AD, and to assess its potential as a biomarker of disease progression.MethodsResting-state fMRI data from 40 NC, 38 MCI, and 40 AD participants from ADNI 2/3 were preprocessed using SPM12 and FSL, including motion correction (FD < 0.5 mm). Mean time series were extracted from 300 regions of the seven-network Schaefer atlas. For each subject, a 300 × 300 CRBEN matrix was computed and decomposed using BrainSpace to obtain functional gradients, aligned via Procrustes analysis. Group differences were tested with two-sample t-tests controlling for age, sex, and education (Bonferroni-corrected, α = 0.05). Machine-learning classifiers were trained using gradient and demographic features, with robustness assessed by 1000 bootstrap resamples.ResultsCompared with NC, MCI showed reduced gradients in somatomotor, ventral-attention, and default-mode networks. AD showed further reductions versus MCI in somatomotor and default-mode networks, and versus NC in frontoparietal-control and default-mode networks (p < 0.05, corrected). Logistic regression achieved the highest accuracy (∼90%). Gradient flattening was prominent in temporal and occipital cortices, indicating reduced hierarchical organization.ConclusionsCRBEN gradients demonstrate progressive loss of network complexity across the AD continuum and may provide sensitive biomarkers of functional disintegration.
PMID:41906764 | DOI:10.1177/13872877261431317
Neural correlates of olfactory dysfunction: A systematic review
Neurosci Biobehav Rev. 2026 Mar 27:106665. doi: 10.1016/j.neubiorev.2026.106665. Online ahead of print.
ABSTRACT
Olfactory dysfunction affects over 20% of the population. Despite progress in understanding its neural pathophysiology, research remains fragmented. This systematic review synthesizes evidence of brain structural and functional measures, and their association with clinical characteristics (e.g., etiology, duration) in patients with olfactory dysfunction. This may help to identify neural correlates and potential neuroimaging biomarkers of olfactory dysfunction's severity and progression. Following PRISMA guidelines, we screened 2374 papers and included 164 studies. Structural MRI studies consistently reported reduced olfactory bulb volume and/or sulcus depth, alongside gray matter reduction in the orbitofrontal cortex, hippocampus, insula, and amygdala in acquired olfactory dysfunction and paradoxical increases in congenital anosmia. Diffusion tensor imaging studies showed widespread white matter abnormalities, with prominent fractional anisotropy reductions. Resting-state fMRI demonstrated heterogeneous and global functional connectivity alterations. PET/SPECT studies generally reported reduced perfusion or hypometabolism in frontal regions, especially in the orbitofrontal regions. Dopamine transporter imaging showed more frequent dopaminergic deficits in Parkinson's and prodromal individuals with hyposmia. Electroencephalography studies, despite methodological heterogeneity, generally found prolonged latencies and reduced amplitudes in olfactory event-related potentials. Across techniques, these brain alterations often showed low-to-moderate correlations with olfactory function. Although etiological and methodological heterogeneity currently obstructs the identification of robust neuroimaging biomarkers of olfactory dysfunction's severity and progression, current evidence indicates that olfactory dysfunction involves widespread structural and functional alterations, mainly in olfaction-related areas, with the orbitofrontal cortex as a key area emerging across techniques. Large-scale, standardized studies are needed to enable stratified diagnosis and personalized prognosis.
PMID:41905561 | DOI:10.1016/j.neubiorev.2026.106665
The roles of delayed cortical maturation and lower anticipatory reward activation in predicting addictive screen use in youth
Biol Psychiatry Cogn Neurosci Neuroimaging. 2026 Mar 27:S2451-9022(26)00085-6. doi: 10.1016/j.bpsc.2026.03.012. Online ahead of print.
ABSTRACT
BACKGROUND: Addictive screen use (ASU), above and beyond screen time, has been linked to significant mental health risks. Yet, little is known about the neural risk factors that may associate with ASU. We examined two neurodevelopmental factors-cognitive control and reward-highlighted in substance use research and their links to ASU.
METHOD: We utilized resting-state and monetary incentive delay (MID) task fMRI data from the Adolescent Brain Cognitive Development (ABCD) Study® at baseline (Y0; ages 9-10) to predict addictive videogaming, addictive social media use, addictive phone use, and a composite measure of ASU at year two follow-up (Y2; ages 11-12). Cortical connectomic maturation was operationalized as distance from early-life and proximity to adult functional networks in an individual connectome to potentially index cognitive control development. This was supplemented by also assessing cognitive task performance. Nucleus Accumbens (NAc) activation in anticipation of reward in the MID task was used to assess reward processing.
RESULT: Above and beyond total screen time and attention problems, lower connectomic maturation at Y0 associated with Y2 higher ASU composite and addictive videogaming. Analyses including task performance indicated cortical maturation was associated with both ASU and task performance, but we did not find cognitive task performance to be directly related to ASU. Additionally, lower NAc anticipatory reward activation at Y0 was very weakly associated with higher Y2 ASU.
CONCLUSION: Delayed cortical network maturation and, to a lesser extent, lower anticipatory reward activation in 9-to-10-year-olds may be associated with addictive screen use in early adolescence, above-and-beyond parent-reported attention problems.
PMID:41905476 | DOI:10.1016/j.bpsc.2026.03.012
Aberrant functional connectivity and Granger causality analysis in patients with β-thalassemia major
Ann Hematol. 2026 Mar 28;105(4):210. doi: 10.1007/s00277-026-06893-6.
ABSTRACT
This study aimed to assess alterations in functional connectivity (FC) within brain networks in children and adolescents with β-TM major and to explore the intrinsic relationship between network changes and cognitive impairment. This prospective study recruited 70 patients with β-TM and 64 healthy controls. Cognitive function assessments using Montreal Cognitive Assessment (MoCA) and Modified Mini-Mental State Examination (MMMSE), and hematological parameters were collected. Region of interest (ROI)-to-ROI connectivity analysis was conducted to investigate the whole brain FC within and between resting-state networks. Granger causality analysis was utilized to evaluate the effective interactions among them. Patients exhibited significant cognitive impairment compared to controls. Key hematological indicators, such as serum ferritin, were not found to be correlated with cognitive function. Rs-fMRI revealed extensive reductions in functional connectivity, accompanied by several enhancements. These FCs’ alterations significantly correlated with cognitive deficits. Granger causality analysis further indicated effective information flow from these FCs. This study showed significant correlation of cognitive impairment with aberrant FC in brain networks and hematological parameters in patients with β-TM. These results should advance our understanding of the neural mechanism underlying β-TM-related cognitive dysfunction and may serve as potential neuroimaging biomarkers for cognitive functioning in this population.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00277-026-06893-6.
PMID:41902954 | PMC:PMC13033005 | DOI:10.1007/s00277-026-06893-6
Pallidal and subthalamic stimulations modulate inter-hemispheric interaction and asymmetry in Parkinson's disease
Mol Psychiatry. 2026 Mar 29. doi: 10.1038/s41380-026-03557-9. Online ahead of print.
ABSTRACT
Substantial asymmetries of motor dysfunction are evident in patients with Parkinson's disease (PD), the mechanisms of which remain largely unexplored. This study investigated how deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) and subthalamic nucleus (STN) modulates characteristics of hemispheric lateralization in PD patients, with particular emphasis on motor asymmetries and hemispheric integration (via homotopic functional connectivity) and segregation (via hemispheric asymmetry in connectivity). Resting-state functional magnetic resonance imaging (fMRI) and Unified Parkinson's Disease Rating Scale (UPDRS) III scores were analyzed from 55 PD patients who underwent either bilateral GPi- or STN-DBS. Both targets produced significant improvements in motor function. Notably, stimulation effects on motor asymmetry depend on patients' baseline asymmetry direction (DBS OFF): STN-DBS consistently reduced asymmetry in the leftward-asymmetry patients, whereas GPi-DBS has stronger effects in rightward patients. In both cases, stimulation led to a more symmetric pattern. Beyond motor outcomes, motor gains were associated with changes in homotopic connectivity in the lateral occipital region, overlapping the extrastriate body area, suggesting a compensatory role of visual networks. These findings highlight the contribution of the visual networks to motor improvement and reveal target-dependent effects of DBS on both motor asymmetry and non-motor cognitive domains.
PMID:41904270 | DOI:10.1038/s41380-026-03557-9
Focussed ultrasound thalamotomy and functional MRI as windows to neural networks underlying essential tremor
Neurotherapeutics. 2026 Mar 27:e00893. doi: 10.1016/j.neurot.2026.e00893. Online ahead of print.
NO ABSTRACT
PMID:41904108 | DOI:10.1016/j.neurot.2026.e00893
Positive association between local brain hypercorrelations and posttraumatic stress disorder (PTSD) symptom severity
J Neurophysiol. 2026 Mar 28. doi: 10.1152/jn.00597.2025. Online ahead of print.
ABSTRACT
Previous studies have documented neural network anomalies in posttraumatic stress disorder (PTSD) characterized by hypercorrelated interactions across brain areas, relative to controls. Here we evaluated and compared local, intra-area(s), interactions by computing crosscorrelations derived from prewhitened resting-state 3T fMRI BOLD time series within 84 brain regions (35 cortical areas and 7 subcortical nuclei per hemisphere) in 15 veterans with PTSD and 21 healthy controls. We found that intra-area correlations were significantly higher in PTSD, as compared to controls, indicating a restriction in local network flexibility. PTSD symptom severity was positively and significantly associated with increased local correlations, most prominently in frontal and limbic areas.
PMID:41902519 | DOI:10.1152/jn.00597.2025