Most recent paper

Hum Brain Mapp. 2026 Jul;47(10):e70596. doi: 10.1002/hbm.70596.

ABSTRACT

Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model-based support that reductions in the structure-function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom-up and reduced top-down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.

PMID:42381187 | DOI:10.1002/hbm.70596

BMC Psychiatry. 2026 Jun 30. doi: 10.1186/s12888-026-08337-x. Online ahead of print.

NO ABSTRACT

PMID:42380794 | DOI:10.1186/s12888-026-08337-x

J Psychiatr Res. 2026 Jun 26;201:400-408. doi: 10.1016/j.jpsychires.2026.06.048. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Post-traumatic stress disorder (PTSD) is associated with increased risk of cognitive impairment (CI), but how large-scale network disruption relates to this vulnerability remains unclear. We examined whether PTSD and cognitive status interact to shape brain network organization.

METHODS: Resting-state fMRI from 178 age-matched male participants (ADNI-DOD and ADNI cohorts) was analyzed within a 2 × 2 factorial design defined by PTSD status and cognitive status. Cognitive status was classified using the Montreal Cognitive Assessment (MoCA), with CI defined by a MoCA score of 18-26 and cognitively normal (CN) status by a MoCA score >26, yielding four groups; PTSD status was established using the Clinician-Administered PTSD Scale (CAPS), requiring a score ≥40 for the PTSD group and ≤30 for non-PTSD (NPTSD) controls. These criteria yielded four groups: PTSD-CI (n = 46), PTSD-CN (n = 14), NPTSD-CI (n = 55), and NPTSD-CN (n = 63). Functional connectivity matrices (32 regions, Harvard-Oxford atlas) underwent graph-theoretical analysis. General linear models tested main effects and the PTSD × cognitive status interaction for global efficiency, eigenvector centrality, clustering coefficient, local efficiency, degree, and betweenness centrality, adjusting for age, education, APOE ε4 status, and depressive symptoms (FDR-corrected).

RESULTS: A significant PTSD × cognitive status interaction was observed across all four dorsal attention network (DAN) nodes-bilateral frontal eye fields and intraparietal sulci-for global efficiency, eigenvector centrality, cost, and degree. These effects were driven exclusively by PTSD-CI versus PTSD-CN differences and were absent in non-PTSD groups, reflecting a reversal of the normally right-lateralized DAN organization. Further interaction effects emerged in the right supramarginal gyrus (salience network) and medial visual network. A PTSD main effect reduced language-network hub function (left inferior frontal gyrus, left posterior superior temporal gyrus), and a cognitive-status main effect involved the left supramarginal gyrus.

CONCLUSIONS: PTSD and cognitive impairment interact, rather than summate, to produce a distinct network signature characterized by DAN lateralization reversal, identifying PTSD-CI as a neurobiologically distinct phenotype and highlighting the DAN, salience, and language networks as targets.

PMID:42379073 | DOI:10.1016/j.jpsychires.2026.06.048

Exp Gerontol. 2026 Jun 30:113220. doi: 10.1016/j.exger.2026.113220. Online ahead of print.

ABSTRACT

OBJECTIVE: Tinnitus and chronic pain, as two perceptual disorders frequently accompanied by negative emotions, significantly impair patients' daily functioning and overall well-being. However, the neurophysiological mechanisms that account for their frequently observed clinical similarities have yet to be fully elucidated.

METHODS: The study enrolled a total of 56 participants, including 18 tinnitus patients and 19 chronic pain patients, alongside 19 healthy controls. We computed the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) from resting-state fMRI data to quantify localized brain activity intensity and neural synchronization.

RESULTS: Statistical analysis suggested a significant elevation in fALFF within the calcarine cortex of tinnitus patients compared to healthy controls (p < 0.05, FDR-corrected). In contrast, chronic pain patients exhibited notable increases in both fALFF and ReHo in the inferior frontal gyrus (IFG). Direct comparisons between patient groups suggested that tinnitus patients had higher fALFF in the inferior temporal gyrus (ITG), supplementary motor area and fusiform gyrus, but lower fALFF in the right IFG, precuneus, and caudate nucleus. Regarding ReHo, patients with tinnitus exhibited significantly elevated ReHo values in the supplementary motor area, while demonstrating reduced ReHo in both the precuneus and caudate nucleus (all p < 0.05, FDR-corrected).

CONCLUSION: The observed differences between tinnitus and chronic pain in brain regions including the prefrontal cortex, ITG, and fusiform gyrus provide neuroimaging correlates associated with the two conditions. These findings may inform future neuromodulation targets and support clinical differential diagnosis.

PMID:42379384 | DOI:10.1016/j.exger.2026.113220

Int Rev Psychiatry. 2026 Jun 30:1-10. doi: 10.1080/09540261.2026.2687523. Online ahead of print.

ABSTRACT

The frontal pole is a transdiagnostic target for affective disorders, perhaps through its connectivity with affective regions like the amygdala. Recent work shows that single-pulse or single-session transcranial magnetic stimulation (TMS) to the frontal pole (FP) modulates amygdala activity and frontoamygdala connectivity. In a secondary analysis of a double-blind, Sham-controlled clinical trial, 17 participants with alcohol use disorder (10 Real, 7 Sham; 24% Female; age 46 ± 13 years) received 10 sessions of continuous theta burst stimulation (cTBS) to the left frontal pole (FP1). Resting-state fMRI was acquired pre-treatment, post-treatment (within one week of treatment completion), and 1 month after treatment. Voxelwise mixed-effects modeling revealed that Real cTBS, compared to Sham, selectively decreased connectivity between the frontal pole and the medial amygdala. Using an ANCOVA approach to account for regression to the mean, this reduction was confirmed to be durable over the 1-month follow-up and was most pronounced in participants exhibiting the highest baseline connectivity. These results extend knowledge on amygdala modulation and set the stage for future work to access the amygdala through the frontal pole for affective disorders marked by amygdala dysregulation.

PMID:42379239 | DOI:10.1080/09540261.2026.2687523

Neurosurgery. 2026 Jun 30. doi: 10.1227/neu.0000000000004146. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Cervical spondylotic myelopathy (CSM) is a leading cause of spinal cord dysfunction, yet the central neural mechanisms underlying motor impairment and recovery remain unclear.

METHODS: This study used the first 7 T functional MRI (fMRI) study in patients with CSM to investigate sensorimotor network alterations. Sixteen patients with CSM and age-matched healthy controls underwent task-based fMRI during hand grasping and resting-state fMRI. Ten patients completed 3-month postoperative follow-up imaging. Clinical severity was assessed using Japanese Orthopaedic Association (JOA) scores.

RESULTS: Task-based fMRI during hand movements revealed compensatory bilateral recruitment in patients with CSM compared with controls, with significantly increased activation in the ipsilateral primary motor cortex (M1; peak: 45, -21, 56; T = 7.93, P < .001) and contralateral cerebellum (peak: -21, -52, -28; T = 7.23, P < .001). Cerebellar hyperactivation correlated negatively with JOA total scores (peak: -26, -56, -24; T = 10.74, P < .001) and dexterity subscales (T = 9.05, P < .001), indicating severity-dependent compensation. Resting-state analysis revealed widespread increases in sensorimotor network connectivity. The strongest alterations were observed in bilateral M1 connectivity (T = 14.65, P < .001), bilateral primary sensory cortex connectivity (T = 14.53, P < .001), and M1-supplementary motor area (SMA) connections (right M1 to left SMA: T = 13.21, P < .001; bilateral SMA: T = 13.89, P < .001). Intracerebellar networks showed marked hyperconnectivity (bilateral cerebellar lobule VI: T = 15.35, P < .001; bilateral cerebellar lobule IV-V: T = 14.25, P < .001). Resting-state connectivity strength was negatively correlated with both JOA total scores and dexterity subscales.

CONCLUSION: This 7T fMRI study reveals that CSM induces compensatory reorganization involving the contralateral cerebellum and ipsilateral motor cortex, with severity-dependent hyperconnectivity. These findings clarify mechanisms of motor compensation and suggest cerebellar-focused rehabilitation as a potential therapeutic strategy.

PMID:42377928 | DOI:10.1227/neu.0000000000004146

J Neural Transm (Vienna). 2026 Jun 30. doi: 10.1007/s00702-026-03217-w. Online ahead of print.

ABSTRACT

Levodopa-induced dyskinesia (LID) is a major source of disability in advanced Parkinson's disease (PD), whose impact on gait and balance across medication states still remains unclear. We aimed to compare gait and balance performance between comparable dyskinetic (Dysk-matched) and non-dyskinetic (No-Dysk) PD patients in OFF and ON state, and to explore neural correlates using structural and resting-state functional MRI (rs-fMRI). PD patients were consecutively enrolled among candidates for device-aided therapies. Gait and balance were assessed using validated wearable inertial sensors during a 2-minute walk test, a 3-meters Timed-Up-and-Go (TUG), and a sway test, providing spatiotemporal gait parameters, variability, asymmetry, and postural sway metrics. Groups were compared using propensity score matching (PSM) for age, sex, disease duration, motor severity and axial disability. A subgroup underwent exploratory investigation with structural and rs-fMRI collected in ON state. After PSM (22 pairs), Dysk-matched group showed slower gait speed (p = 0.007), shorter stride length (p = 0.006), longer double support (p = 0.047), and prolonged TUG (p = 0.049) in the OFF state. Dysk-matched patients showed increased sway from OFF to ON (p = 0.030). Neuroimaging (10 Dysk-matched, 9 No-Dysk) revealed increased functional connectivity in sensorimotor regions and reduced SMA connectivity within a cerebellar network in Dysk-matched patients, without structural difference. Overall, the association of LID with impaired gait and postural control even in the OFF state is consistent with the hypothesis of broader motor network dysfunction beyond overt involuntary movements.

PMID:42377454 | DOI:10.1007/s00702-026-03217-w

J Alzheimers Dis. 2026 Jun 30:13872877261462932. doi: 10.1177/13872877261462932. Online ahead of print.

ABSTRACT

BackgroundDepressive symptoms frequently co-occur with cognitive impairment in older adults. Although depression and cognition interact in brain activity, the underlying functional connectivity mechanisms in mild cognitive impairment (MCI) remains unclear.ObjectiveTo investigate how depressive symptoms modulate the relationship between cognition and amygdala/hippocampus functional connectivity in MCI.MethodsThis study included 138 participants (45 healthy controls and 93 MCI patients) who underwent resting state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessment using the Montreal Cognitive Assessment-Basic (MoCA-B) for cognitive function and Hamilton Depression Rating Scale (HAMD) for depressive symptoms. Seed-based functional connectivity analysis was performed using bilateral amygdala and hippocampus as seed regions to quantify the HAMD × MoCA-B non-monotonic interactions on whole-brain connectivity. Simple slopes analyses were conducted to characterize directionality changes across depression severity levels.ResultsWhole-brain analyses revealed significant HAMD × MoCA-B interaction effects (cluster p value < 0.05, voxel p value < 0.01, GRF corrected) demonstrating symptom-dependent reorganization of cognition-FC relationships. Amygdala connectivity decreased to anterior/middle cingulate and precuneus but increased to triangular part of inferior frontal gyrus (IFGtri), medial superior frontal gyrus, and cerebellar lobule IX. Hippocampal connectivity decreased to cuneus, insula, thalamus, and caudate but increased to opercular part of inferior frontal gyrus (IFGop), orbitofrontal cortex, and cerebellar lobule VIII.ConclusionDepressive symptoms alter amygdala and hippocampal FC relationships with cognition in MCI. Depression-dependent hippocampal/amygdala connectivity changes with the frontoparietal network (FPN-A)-particularly IFGop/IFGtri and cerebellum-suggest their role as critical hubs for emotional-cognitive integration, highlighting them as potential neuromodulation targets for cognitive and depressive symptoms in MCI.

PMID:42377424 | DOI:10.1177/13872877261462932

Hum Brain Mapp. 2026 Jul;47(10):e70597. doi: 10.1002/hbm.70597.

ABSTRACT

Passive working memory (WM) is rarely detectable because it is thought to rely less on persistent neural firing, leaving a minimal trace in ongoing brain activity. This elusive nature poses a major challenge for exploring its neural basis. While the activity-silent working memory (ASWM) framework proposes that such latent representations are maintained through transient reconfiguration in intrinsic functional connectivity, tracking these rapid dynamics via functional MRI remains methodologically difficult. Alternatively, investigating the brain's intrinsic functional architecture provides insights into the baseline "neural scaffolding" that predisposes individuals to successful passive WM. To explore this, we combined pre-task resting-state fMRI, structural MRI, and behavioral data from a sequential change-detection paradigm in 151 healthy adults. Functional connectivity-behavior associations revealed that individual differences in passive WM performance were significantly reflected by intrinsic connections among large-scale networks encompassing dorsal attention, control, and sensorimotor. Granger causality analyses further revealed a group-level temporal dependency pattern linking these functional systems. Furthermore, exploratory structural analyses suggested spatial convergence between uncorrected cortical-thickness associations and certain functionally identified sensorimotor nodes. Overall, this study adopts an exploratory approach to demonstrate that baseline intrinsic functional architecture-complemented by preliminary structural findings-is significantly associated with individual differences in passive WM.

PMID:42376739 | DOI:10.1002/hbm.70597

Int J Clin Health Psychol. 2026 Apr-Jun;26(2):100700. doi: 10.1016/j.ijchp.2026.100700. Epub 2026 Jun 17.

ABSTRACT

BACKGROUND/OBJECTIVE: During childhood and adolescence, functional connectivity undergoes distinct age-related maturational trajectories within and between networks. However, normative connectivity patterns across development remain insufficiently characterized.

METHODS: This study integrates voxel-wise degree centrality, degree centrality-derived seed-based connectivity, and network-level analyses to examine large-scale functional organization in a large multisite sample of 322 typically developing children (7-10.99 years) and adolescents (11-15 years) from the Autism Brain Imaging Data Exchange I and II repositories.

RESULTS: Across all analytical levels, adolescents exhibited strengthened functional connectivity of subcortical hubs -the thalamus and the basal ganglia- with the Ventral Attention Network and Frontoparietal Network, emerging as the key hubs of network integration in adolescence. Children, by contrast, showed stronger functional connectivity within posterior sensory-perceptual nodes, particularly involving angular and occipital regions.

CONCLUSIONS: Our findings delineate a developmental reorganization from sensory-anchored functional architectures in childhood toward increasingly integrated subcortical, attentional and frontoparietal systems in adolescence, supporting emerging capacities for cognitive-control and goal-directed behavior. This multilevel characterization offers a normative reference framework for interpreting variability in neurodevelopment and, ultimately, for identifying potential early deviations.

PMID:42376368 | PMC:PMC13311167 | DOI:10.1016/j.ijchp.2026.100700

Front Neurosci. 2026 Jun 15;20:1734858. doi: 10.3389/fnins.2026.1734858. eCollection 2026.

ABSTRACT

INTRODUCTION: Cortical and subcortical alterations in brain intrinsic function have been widely reported in Parkinson's disease (PD). However, sex differences in brain intrinsic function in PD are poorly understood. This study aimed to examine sex differences in spontaneous brain intrinsic function in PD and their associations with neuropsychological measurements.

METHODS: Using Parkinson's Progression Markers Initiative (PPMI) resting-state fMRI, we compared amplitude of low-frequency fluctuations (ALFF) between male and female PD patients in substantia nigra (SN), globus pallidus (GP) and whole-brain. Subgroup analysis was performed, matching demographics with equal sample sizes. ALFF correlations with behavior were assessed by sex.

RESULTS: Female PD patients demonstrated higher ALFF in the right SN compared to males in the primary analysis. This sex difference achieved statistical significance in the demographics-matched subgroup analysis. Bilateral premotor ALFF was significantly elevated in female patients relative to males, independent of brain structure. Furthermore, right premotor ALFF showed a preliminary positive trend associated with visuospatial function exclusively in female PD patients.

CONCLUSION: Female PD patients exhibit distinct functional signatures, primarily involving elevated premotor fluctuations and a preliminary premotor-visuospatial association. Preliminary SN alterations were also noted. These findings highlight the necessity of sex-stratified neuroimaging and provide preliminary support for premotor ALFF as a potential sex-divergent functional signature associated with cognitive profiling in female patients with PD.

PMID:42375632 | PMC:PMC13310980 | DOI:10.3389/fnins.2026.1734858

Hum Brain Mapp. 2026 Jul;47(10):e70582. doi: 10.1002/hbm.70582.

ABSTRACT

Many symptoms of posttraumatic stress disorder (PTSD) overlap with the psychological sequelae of tinnitus, including sleep difficulty, concentration problems, hypervigilance, and irritability. Although these two disorders are clearly distinct, they are highly comorbid, may have shared etiology, and are among the top service-connected disabilities within the VA healthcare system. This study aimed to determine neuropathophysiological similarities and differences among veterans with both PTSD and tinnitus, tinnitus only, and healthy controls. Resting-state networks were identified by previous studies and extracted to examine functional connectivity patterns. Networks included the default mode network (DMN), auditory vigilance (AUDVIG), salience (SN), dorsal attention (DAN), and emotion (EMO) networks. Functional connectivity among specific brain regions was decreased among the tinnitus only group compared to the healthy control group and was further decreased when PTSD was present with tinnitus. Findings suggest that the additive and negative effects observed symptomatically may be explained by decreased functional connectivity, especially with respect to the DMN and AUDVIG networks.

PMID:42374873 | DOI:10.1002/hbm.70582

Alzheimers Res Ther. 2026 Jun 27. doi: 10.1186/s13195-026-02125-1. Online ahead of print.

ABSTRACT

BACKGROUND: The medial temporal lobe is organized into two memory-critical networks: the anterior-temporal and posterior-medial systems. While these systems show selective vulnerability to aging and Alzheimer's disease, the underlying structural and molecular determinants of this susceptibility remain unclear. We aimed to characterize the specific white matter pathways supporting these networks, investigate how amyloid-β and neuroinflammation interact to impact their integrity, and determine if structural changes relate to functional connectivity alterations.

METHODS: In 88 cognitively unimpaired (CU) older adults (≥ 65 years) from the Age-Well cohort (NCT02977819), we combined longitudinal diffusion MRI tractography, resting-state fMRI, amyloid-β PET (Florbetapir), and plasma glial fibrillary acidic protein (GFAP). We reconstructed fiber pathways of the perirhinal (anterior-temporal system hub) and parahippocampal (posterior-medial system hub) cortices and quantified their microstructural integrity, network connectivity, and relationships to pathology.

RESULTS: The anterior-temporal and posterior-medial systems relied on partly distinct structural pathways. Both involved the inferior longitudinal and cingulum bundles, but the anterior-temporal system was specifically associated to their inferior portions, as well as thalamic radiations, and callosal fibers, whereas the posterior-medial system relied more on their superior portions and the inferior fronto-occipital fasciculus. We identified a non-linear, inverted U-shaped association between pathway integrity and amyloid-β burden, suggesting dynamic structural changes across early pathological stages. Crucially, plasma GFAP moderated this relationship for the posterior-medial pathway: the negative impact of amyloid-β on structural integrity was exacerbated in individuals with higher astroglial reactivity, highlighting a synergistic pathological effect. Finally, in high amyloid-β individuals, increased anterior-temporal functional connectivity correlated with lower anterior-temporal pathway integrity, suggesting that network higher FC may represent a maladaptive response to early amyloid-β deposition leading to white matter integrity loss.

CONCLUSIONS: Together, our findings reveal distinct mechanisms of vulnerability within medial temporal networks: while the posterior-medial system is primarily sensitive to the synergistic effects of amyloid-β and astroglial reactivity, the anterior-temporal system shows lower structural integrity linked to higher FC in the presence of amyloid. By providing a mechanistic framework for these early disruptions, this study advances the understanding of preclinical Alzheimer's disease and identifies specific structural-functional signatures that could serve as sensitive biomarkers for targeted interventions.

PMID:42374489 | DOI:10.1186/s13195-026-02125-1

Sci Rep. 2026 Jun 29. doi: 10.1038/s41598-026-59962-1. Online ahead of print.

ABSTRACT

The hippocampus and amygdala form a tightly integrated circuit supporting memory-emotion integration and stress regulation, critically implicated in psychosis development. However, the maturation of the hippocampus-amygdala (HIP-AMY) complex as a functional unit remains poorly understood. 22q11.2 deletion syndrome (22q11DS), with increased risk of schizophrenia, provides a valuable model to study its neurodevelopmental trajectories. A prospective longitudinal cohort of 133 individuals with 22q11DS and 150 healthy controls (HC) underwent neuroimaging and psychiatric assessments approximately every three years. Resting-state fMRI data were analysed using a data-driven clustering approach to identify transient states of dynamic functional connectivity linked to the activation of specific ensembles of HIP-AMY nuclei. State occurrences over age were compared between 22q11DS and HC and between 22q11DS individuals with and without positive psychotic symptoms (PPS+ and PPS-). Seven HIP-AMY states were identified, three showing significant and one trend-level age-by-diagnosis interaction. Importantly, the occurrence of a CA3-centromedial amygdala driven state showing co-activation of limbic and thalamo-striatal salience hubs decreased over age in HC, but remained elevated in 22q11DS. This divergence was reflected within 22q11DS, with PPS- showing a decrease and PPS+ a modest increase. The persistence of this pattern over development may provide a dynamic signature of emergence of psychosis.

PMID:42374122 | DOI:10.1038/s41598-026-59962-1

Sci Rep. 2026 Jun 29. doi: 10.1038/s41598-026-58431-z. Online ahead of print.

ABSTRACT

Predicting behavioral and personality traits from neuroimaging data requires effective modeling of complex and high-dimensional brain dynamics. Although recent advances in neurocomputations have paved the way for trait prediction models, the attempts remain at a nascent stage, as reflected in the moderate prediction accuracies. To this end, in this work, we propose a novel unified framework that leverages both spatial and temporal information derived from resting-state functional MRI (rs-fMRI) for trait prediction. Task-activation maps are first estimated directly from rs-fMRI, providing spatial representations of task-evoked brain activity without requiring explicit task paradigms. To capture temporal dynamics, MultiRocket, an efficient time-series feature-extraction method, is employed, encoding trait-specific patterns in rs-fMRI signals. The spatial and temporal features are then fused to form a unique unified spatio-temporal representation that is subsequently provided to an ensemble framework to predict cognitive traits, viz., reading ability, fluid intelligence, and processing speed, and personality traits, viz., openness to experience and extraversion. Experimental validation of the proposed framework on the HCP dataset demonstrates superior predictive performance, achieving state-of-the-art correlations of up to 0.5284, thereby highlighting the importance of the proposed spatio-temporal modeling for understanding brain-behaviour relationships.

PMID:42374074 | DOI:10.1038/s41598-026-58431-z

Prog Neuropsychopharmacol Biol Psychiatry. 2026 Jun 29:111798. doi: 10.1016/j.pnpbp.2026.111798. Online ahead of print.

ABSTRACT

Chronic pain is increasingly conceptualized within a stress-related framework. However, it remains unclear whether chronic pain and prototypical stress-related conditions-such as post-traumatic stress disorder (PTSD)-show convergence in their morphometric alterations and underlying normative functional connectivity profiles. To this end, we conducted a pre-registered transdiagnostic meta-analytic study of gray matter volume alterations in chronic pain (60 studies) and PTSD (20 studies), testing convergence at two complementary levels: direct anatomical overlap and network-level convergence within normative resting-state functional systems. Disorder-specific meta-analyses revealed that chronic pain was associated with distributed volume reductions across ventromedial prefrontal, middle cingulate, and insular cortices, whereas PTSD exhibited a single cluster of reduced volume in the anterior cingulate/dorsomedial prefrontal cortices. A direct conjunction analysis identified a spatially focal overlapping cluster of reduced volume in the bilateral medial orbitofrontal/anterior cingulate area. Importantly, using normative resting-state fMRI data (HCP 7 T dataset), we found that the disorder-specific structural abnormalities were embedded within partially overlapping large-scale systems. Specifically, chronic pain abnormalities were embedded within a distributed architecture of large-scale circuits encompassing mesocorticolimbic/reward, default mode, salience, frontoparietal, dorsal attention, and somatosensory networks. On the other hand, the PTSD focal neuroanatomical alteration was embedded in a single large-scale circuit mapping onto the mesocorticolimbic/reward, default mode, salience, and visual networks. In both conditions, the mesocorticolimbic/reward circuit emerged as the most robustly involved large-scale network. Notably, the shared cluster of reduced volume showed functional integration within the mesocorticolimbic/reward and default mode networks, with neurochemical fingerprinting revealing robust spatial correspondence with dopaminergic, serotonergic, opioid, and endocannabinoid receptor/transporter maps. Overall, these findings indicate that brain morphological alterations in chronic pain and PTSD converge in a focal medial prefrontal/anterior cingulate region and that disorder-specific abnormalities map onto partially overlapping normative functional networks, particularly involving the mesocorticolimbic/reward-related system, the default mode network, and the salience network. This network-level convergence is consistent with the hypothesis that chronic pain may, at least in part, be conceptualized within a stress-related framework.

PMID:42373038 | DOI:10.1016/j.pnpbp.2026.111798

Res Sq [Preprint]. 2026 Jun 1:rs.3.rs-9613537. doi: 10.21203/rs.3.rs-9613537/v1.

ABSTRACT

Social recognition, the ability to distinguish between individuals, is essential for cognitively demanding social behaviors. The anterior olfactory nucleus (AON), a primary olfactory cortical region, is implicated in this process, but the underlying neurocircuitry remains poorly understood. Here, we generated a novel mouse line to enable genetic access to AON pyramidal neurons and mapped their whole-brain synaptic inputs and outputs. The medial prefrontal cortex (mPFC), a crucial hub for social cognition, is the primary neocortical target of AON neurons, which form monosynaptic excitatory connections with a substantial fraction of mPFC neurons. The AON→mPFC pathway is activated during social investigation, and chemogenetic inhibition of this pathway impairs social recognition. Moreover, an analogous AON-prefrontal pathway is present in humans, as supported by resting-state functional magnetic resonance imaging (fMRI) functional connectivity analyses. Taken together, these findings reveal a conserved olfactory-prefrontal circuit spanning mice to humans, potentially linking olfactory dysfunction to neuropsychiatric disorders.

PMID:42370285 | PMC:PMC13308722 | DOI:10.21203/rs.3.rs-9613537/v1

Front Neurol. 2026 Jun 11;17:1831863. doi: 10.3389/fneur.2026.1831863. eCollection 2026.

ABSTRACT

OBJECTIVE: This study aimed to characterize resting-state functional differences across clinically defined bothersome tinnitus, non-bothersome tinnitus, and hospital-based non-tinnitus control groups, focusing on imaging differences related to tinnitus phenotype.

METHODS: This case-control study included 61 patients with bothersome tinnitus (BT), 52 with non-bothersome tinnitus (NBT), and 50 hospital-based non-tinnitus controls. Resting-state fMRI scans were acquired, and the data were analyzed using fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and seed-based functional connectivity (FC) using broad bilateral temporal lobe regions of interest to assess temporal-related network connectivity, including temporal-limbic interactions. Group comparisons were performed using ANCOVA controlling for demographic, audiological, physiological, sleep-related, and emotional covariates, cluster-level FDR-corrected p < 0.05. Exploratory correlation analyses were further conducted to examine associations between extracted imaging indices and clinical measures, as well as potential relationships among significant imaging findings.

RESULTS: Resting-state fMRI revealed significant group differences in functional connectivity between the bilateral temporal lobe seed and the left ACC/mOFC cluster. Post hoc analyses showed stronger connectivity in BT than in NBT, whereas BT did not differ significantly from hospital-based non-tinnitus controls. A similar pattern was observed for ReHo in the medial superior frontal gyrus, with lower values in NBT than in both BT and controls. fALFF analyses showed region-specific differences across temporal, frontal, insular, occipital, supramarginal, and postcentral regions, with the most consistent differences observed between BT and NBT. Exploratory analyses showed no significant FC-ReHo correlation within the BT group, and no associations between imaging indices and clinical or audiological measures survived FDR correction. In sensitivity analyses retaining the original covariate structure and additionally adjusting for tinnitus loudness VAS, most BT-NBT differences were attenuated, suggesting that these imaging differences may partly reflect tinnitus loudness or related clinical burden.

CONCLUSION: Resting-state FC, fALFF, and ReHo measures revealed phenotype-related functional differences between BT and NBT. Because several key measures did not differ between BT and hospital-based non-tinnitus controls, these findings should be interpreted as group-level imaging features across tinnitus phenotypes, not as BT-specific abnormalities.

PMID:42369362 | PMC:PMC13293808 | DOI:10.3389/fneur.2026.1831863

Front Psychiatry. 2026 Jun 12;17:1833948. doi: 10.3389/fpsyt.2026.1833948. eCollection 2026.

ABSTRACT

BACKGROUND: Aberrant interhemispheric functional connectivity has been implicated in the pathophysiology of schizophrenia. Voxel-mirrored homotopic connectivity (VMHC) provides a reliable measure of interhemispheric synchronization, yet the frequency-specific characteristics of VMHC alterations in schizophrenia remain poorly understood.

METHODS: Resting-state functional magnetic resonance imaging data were analyzed in patients with schizophrenia and matched healthy controls. VMHC was computed across frequency bands, with particular focus on slow-4 and slow-5 oscillations. Group differences, as well as group-by-frequency interactions, were assessed to identify frequency-specific disruption.

RESULT: Patients with schizophrenia exhibited significantly reduced VMHC within key sensory networks, including primary visual and sensorimotor regions. Frequency-specific analyses revealed higher VMHC at slow-5 compared with slow-4 in visual gyrus and subcortical regions. Significant group-by-frequency interaction effects were observed in the middle occipital gyrus and postcentral gyrus, with post-hoc analyses indicating selectively reduced slow-4 VMHC in patients with schizophrenia.

CONCLUSION: This study demonstrates frequency-dependent reductions of interhemispheric connectivity in schizophrenia, particularly within sensory systems. The findings highlight the disrupted integration of primary perceptual and motor-related processes as a core feature of schizophrenia and emphasize the utility of frequency-resolved VMHC analyses for refining our understanding of network dysfunction. Future longitudinal studies are warranted to determine the clinical significance of these frequency-specific alterations in illness progression and treatment response.

PMID:42368798 | PMC:PMC13303831 | DOI:10.3389/fpsyt.2026.1833948

Front Behav Neurosci. 2026 Jun 12;20:1821101. doi: 10.3389/fnbeh.2026.1821101. eCollection 2026.

ABSTRACT

INTRODUCTION: Transcranial alternating current stimulation (tACS) has emerged as a promising tool to modulate cognitive functions by entraining endogenous neural oscillations. This study investigated the behavioral and neurophysiological after-effects of theta-frequency tACS individualized to each participant's intrinsic theta frequency (ITF).

METHODS: Twenty-two healthy participants were randomly assigned to either a real stimulation group (tACS group) or a sham group. Cognitive assessments and resting-state EEG/fMRI data were collected pre- and post-stimulation.

RESULTS: Participants in the real tACS group showed significant post-stimulation improvements in short-term memory, verbal fluency and category fluency scores compared to the sham group. Functional connectivity analyses revealed increased activity in the dorsal attention and frontoparietal networks only in the stimulation group, suggesting network-specific modulation.

DISCUSSION: These effects align with the theta-gamma coupling theory and provide evidence for long-lasting neuroplastic changes following personalized tACS. This study contributes to our understanding of brain stimulation and supports the use of tACS for cognitive enhancement in healthy individuals.

PMID:42368749 | PMC:PMC13303487 | DOI:10.3389/fnbeh.2026.1821101