Most recent paper

Front Psychiatry. 2026 Jul 27;17:1843959. doi: 10.3389/fpsyt.2026.1843959. eCollection 2026.

ABSTRACT

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often-but not always-characterized by inattention, hyperactivity/impulsivity, and deficits in executive functions (EFs); some individuals may also exhibit sensorimotor dysfunction. While SMN dysfunction has been implicated in ADHD, the patterns of SMN functional connectivity (FC) and their relationships with clinical symptoms and EFs remain inconsistent, partly due to methodological heterogeneity.

METHODS: The study included 62 medication-naïve patients with ADHD (aged 6-15 years) and 46 healthy controls matched for age, sex, and IQ. Clinical symptoms and EFs were assessed using CPRS, IVA-CPT, and Stroop tests. Resting-state fMRI data were acquired, and ROIs within SMN, SN, DMN, and FPN were selected from the Dosenbach atlas. FC was analyzed using Network-Based Statistics (NBS). Partial correlations explored FC-behavior relationships in the ADHD group, controlling for age, sex, and IQ.

RESULTS: The ADHD group showed significantly higher CPRS hyperactivity/impulsivity scores and poorer IVA-CPT and Stroop performance. Compared to controls, ADHD showed increased FC within SMN (right posterior insula to left precentral gyrus/parietal lobe), between SMN-DMN (precentral gyrus, dorsal frontal cortex, temporal lobe, angular gyrus, posterior cingulate cortex, and precuneus), and SMN-SN (middle insula, superior parietal lobule, superior temporal gyrus, basal ganglia, and fusiform gyrus). Enhanced intra-SMN FC was negatively correlated with impulsivity/hyperactivity and hyperactivity index scores. Enhanced SMN-DMN FC was negatively correlated with hyperactivity symptoms and positively correlated with control quotients in IVA-CPT. Enhanced SMN-SN FC was negatively correlated with Stroop correct responses and positively correlated with omission errors.

CONCLUSIONS: In this medication-naïve pediatric sample, distinct SMN connectivity patterns differentially related to ADHD symptoms and executive function. However, given the cross-sectional design and modest sample size, these associations cannot establish causality; they require replication in longitudinal studies and larger cohorts to clarify whether they reflect developmental variation, neurobiological subtypes, or epiphenomena.

PMID:42577345 | PMC:PMC13454290 | DOI:10.3389/fpsyt.2026.1843959

Small. 2026 Aug 10:e75162. doi: 10.1002/smll.75162. Online ahead of print.

ABSTRACT

Peripheral nerve injury leads to persistent motor and sensory dysfunction and is increasingly recognized to induce alterations in central sensorimotor networks. However, most current repair strategies primarily focus on peripheral regeneration, with limited understanding of its relationship to central neural changes. Here, we performed clinical resting-state functional magnetic resonance (rs-fMRI) in patients with facial nerve injury and identified the sensorimotor network alterations associated with the nerve injury. Guided by the results, we developed a tissue-engineered fibrous nerve guidance conduit (NGC) integrating aligned nanofibers, sustained nerve growth factor delivery, and Schwann-like cells derived from bone marrow mesenchymal stem cells. In vitro, the combined biochemical and cellular cues enhanced neurite extension. In a rat facial nerve injury model, implantation of the Schwann-like cells-loaded tissue-engineered NGC promoted axonal regeneration and remyelination, achieving facial motor function recovery comparable to autografts. Moreover, rs-fMRI and voxel-based morphometric analyses revealed that peripheral nerve repair with the engineered conduit was accompanied by enhanced functional connectivity within the sensorimotor network and normalization of gray matter alterations. Taken together, these results suggest that biomaterial-assisted nerve repair may extend beyond local regeneration to influence central network dynamics, highlighting a strategy for integrating peripheral repair with central functional reorganization.

PMID:42574217 | DOI:10.1002/smll.75162

Mov Disord. 2026 Aug 9. doi: 10.1002/mds.70461. Online ahead of print.

ABSTRACT

BACKGROUND: Longitudinal studies of seed-based functional connectivity (SBFC) in young adult Huntington's disease gene-expanded (HDGE) individuals are rare, and none, to our knowledge, have examined adult cohorts decades from predicted clinical motor diagnosis.

OBJECTIVES: To examine longitudinal functional connectivity (FC) changes over ~4.8 years in adult HDGE individuals before clinical motor diagnosis compared with matched controls, all selected from the HD Young Adult Study (HD-YAS) cohort, focusing on bilateral caudate and putamen as seeds.

METHODS: A subset of 71 right-handed individuals (43 HDGEs and 28 controls) from the HD-YAS underwent resting-state functional magnetic resonance imaging (fMRI) at two visits ~4.8 years apart. SBFC analyses focused on bilateral caudate and putamen seeds. Mixed-effects analysis of variance (ANOVA) tested main effects of group, time, and group × time interactions, with false discovery rate (FDR) correction. Post hoc tests explored significant findings.

RESULTS: HDGEs showed reduced FC between the putamen and cerebellar vermis/lobules and brainstem (P-FDR ≤ 0.01), alongside increased connectivity with precuneus (P-FDR = 0.04), supramarginal, and angular gyri (P-FDR = 0.04). Over ~4.8 years, HDGEs exhibited different FC trajectories compared with controls, displaying FC reductions between the right caudate and paracingulate, frontal (P-FDR = < 0.001), occipital (P-FDR = < 0.01), and striatal regions (P-FDR = ≤ 0.03).

CONCLUSIONS: These findings provide the first longitudinal evidence of early cortico-striatal and cerebellar functional network changes in adult HDGEs decades before clinical motor diagnosis, alongside possible compensatory processes in key hubs of the default mode network. These early FC changes likely reflect a dynamic interplay between neurodegenerative processes and adaptive reorganization, a balance that may ultimately fail as pathology progresses. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:42571954 | DOI:10.1002/mds.70461

Brain Res. 2026 Aug 9:150483. doi: 10.1016/j.brainres.2026.150483. Online ahead of print.

ABSTRACT

Stroke disrupts the brain's ability to process and integrate information over time, yet the underlying molecular mechanisms remain unclear. This study investigates post-stroke alterations in intrinsic neural timescales (INTs)-a measure of regional temporal integration-by combining resting-state fMRI, spatial transcriptomics, and PET-based neurochemical mapping. Fifty acute ischemic stroke patients (within 7 days of onset) and fifty matched healthy controls were examined. Voxel-wise and network-level analyses revealed significantly reduced INTs in temporoparietal and insular cortices, with pronounced network-level impairments in the visual and cerebellar systems. Using data from the Allen Human Brain Atlas, we identified gene expression patterns associated with these disruptions. Genes negatively associated with INT reductions were enriched for synaptic, mitochondrial, and neurodevelopmental pathways, while positively associated genes reflected immune signaling and nuclear transport. INT alterations also correlated with excitatory and inhibitory neuronal signatures and were spatially aligned with GABA-A receptor density. Importantly, INT reductions showed significant correlations with clinical assessments: whole-brain INT correlated negatively with NIHSS (r = -0.41) and positively with MoCA (r = 0.38) and FMA (r = 0.35); SMN INT correlated with FMA motor subscore (r = 0.44); and regional INT correlated with domain-specific NIHSS subscores (neglect: r = -0.42; language: r = -0.38). These findings position INT as a clinically meaningful systems-level correlate of stroke-induced dysfunction and highlight molecular pathways and neurotransmitter systems that may constrain temporal integration and recovery potential.

PMID:42571842 | DOI:10.1016/j.brainres.2026.150483

J Affect Disord. 2026 Aug 9:122347. doi: 10.1016/j.jad.2026.122347. Online ahead of print.

ABSTRACT

INTRODUCTION: Electroconvulsive therapy (ECT) is the most effective intervention for depression, yet no validated biomarkers reliably predict which patients will remit. Large-scale structural and functional dysconnectivity is well-established in major depressive disorder, motivating the use of graph-theoretical metrics to capture network architecture and identify treatment-sensitive markers.

METHODS: In a prospective longitudinal study, 41 adult patients with a major depressive episode undergoing ECT and 24 healthy controls underwent anatomical, diffusion and resting-state functional MRI at baseline (V1). Patients were reassessed after five ECT sessions (V2, n = 31) and two weeks following treatment completion (V3, n = 29). Structural networks were constructed from multi-shell diffusion tractography and functional networks from rs-fMRI. Longitudinal change of global and local efficiency was assessed using linear mixed-effects models, and baseline predictors of remission (MADRS ≤10 at V3) were evaluated using ANOVAs and penalized binomial regression.

RESULTS: Graph-theory metrics remained stable across timepoints, indicating no large-scale network reorganization during ECT. At baseline, patients showed reduced structural local efficiency relative to controls. Future remitters exhibited lower structural local and global efficiency in fractional anisotropy and neurite density index (NDI)-weighted networks at baseline compared with non-remitters, whereas non-remitters showed reduced functional local efficiency at baseline relative to controls. Penalized regression identified baseline NDI-weighted global efficiency as a significant predictor of remission.

CONCLUSION: Baseline structural and functional network profiles distinguished ECT remitters from non-remitters. These findings suggest that non-remission is characterized by reduced functional integration with relatively preserved structural connectivity, while remission is associated with preserved functional organization but lower baseline structural efficiency.

PMID:42571792 | DOI:10.1016/j.jad.2026.122347

Aging Brain. 2026 Jul 28;10:100162. doi: 10.1016/j.nbas.2026.100162. eCollection 2026.

ABSTRACT

Chronic aerobic exercise is known to protect against brain and cognitive aging in animals, but it remains unclear whether these benefits are consistent across the span of older adulthood. Using time-varying effect modeling (TVEM) analysis, this study investigated how the associations between changes in cognition and brain network functional connectivity (FC), induced by a 6-month aerobic exercise intervention, vary with age among older adults aged 55 to 80 (n = 107). Participants were divided into two groups based on exercise intensity: moderate-to-vigorous (ModVig group) and light-intensity (Light group). Before and after the intervention, participants completed cognitive tasks measuring executive function (EF) and processing speed (PS) and underwent resting-state fMRI sessions. FC was assessed across large-scale brain networks, including the frontoparietal control (FPCN), default mode (DMN), dorsal attention (DAN), limbic (LN), salience (SN), somatomotor (SMN), and visual network (VN). Change scores for each cognitive task and FC network were calculated by subtracting pre-intervention scores from post-intervention scores. Older adults in the ModVig group demonstrated improved PS performance at ages 58 to 65 and increased FC at ages 67 to 69 in the DAN. When individuals were exposed to ModVig intensity exercise, increases in FC within the FPCN, DMN, and SN were associated with improved EF and PS performance in those in their mid-60s to mid-70s. These findings support the importance of targeting higher moderate-to-vigorous aerobic exercise intensity for interventions, particularly in this age group, to enhance brain and cognitive health.

PMID:42569364 | PMC:PMC13450027 | DOI:10.1016/j.nbas.2026.100162

Neuroimage Rep. 2026 Jul 24;6(3):100389. doi: 10.1016/j.ynirp.2026.100389. eCollection 2026 Sep.

ABSTRACT

BACKGROUND: Normal aging is accompanied by cognitive decline, structural and functional brain changes. Cognitive training is a potentially effective intervention for cognitive improvement. Transfer of training gains to untrained tasks is the ultimate goal of cognitive training. However, the neural mechanisms underlying successful transfer remain underinvestigated.

OBJECTIVE: To examine the predictive role of resting-state functional connectivity in the transfer of training gains.

METHODS: We analyzed resting-state fMRI and cognitive data of 181 healthy older adults (mean age: 68 years) who underwent a 4-week cognitive training at three study sites. The control group consisted of 54 older adults. Participants underwent neuropsychological assessments before and directly after the training, as well as 12 weeks after. We used aggregate scores representing working memory, memory and executive functions to assess transfer effects. Baseline resting-state fMRI was used to investigate functional connectivity. We used a seed-based and an independent component analysis approach to examine brain network activity.

RESULTS: The majority of our participants transferred cognitive training gains successfully over a three-month period. Baseline resting-state functional connectivity within the default mode network and the central executive network did not predict transfer of training gains.

CONCLUSIONS: Baseline resting-state functional connectivity of large-scale networks does not appear to predict who will benefit from cognitive training in healthy older adults. These findings contribute to a better understanding of the functional brain mechanisms underlying transfer of training gains and highlight the need for larger, multi-modal neuroimaging studies to identify reliable neural predictors of cognitive training outcomes.

PMID:42569259 | PMC:PMC13449371 | DOI:10.1016/j.ynirp.2026.100389

Front Aging Neurosci. 2026 Jul 24;18:1897104. doi: 10.3389/fnagi.2026.1897104. eCollection 2026.

ABSTRACT

OBJECTIVES: Regular participation in late-life cognitive activities is associated with a reduced risk of dementia. In a prior randomized controlled trial, we demonstrated that increased calligraphy practice improved working memory and strengthened functional connectivity (FC) within the default mode network in older adults with subjective cognitive decline (SCD). This exploratory secondary analysis examined whether increased calligraphy practice also modulates FC in other large-scale brain networks.

METHODS: A total of 112 community-dwelling Chinese adults aged 55-75 years with SCD and prior calligraphy experience were randomly assigned to a control or intervention group. The control group maintained their usual calligraphy practice, while the intervention group doubled their weekly practice time for 6 months. Resting-state FC was assessed at baseline and post-intervention using functional magnetic resonance imaging (fMRI). Mixed models for repeated measures were conducted to compare longitudinal FC changes within the salient network and central executive network between groups.

RESULTS: Compared with the control group, doubling calligraphy practice for 6 months was associated with a significantly greater increase in resting-state FC between right rostral prefrontal cortex and right supramarginal gyrus within the salient network (between-group mean difference = 0.12; 95% CI = 0.03-0.22; p = 0.01). In pooled analyses of the whole sample, no significant pre-post changes in FCs within SAN were observed. No significant between-group FC changes were observed within the central executive network.

CONCLUSION: Increased calligraphy practice was associated with localized FC changes within the salient network, extending our prior findings of more distributed FC changes within the default mode network. Together, these findings suggest late-life engagement in cognitive activities may be relevant to large-scale brain network organization in older adults at risk of dementia.

PMID:42568706 | PMC:PMC13447491 | DOI:10.3389/fnagi.2026.1897104

Hum Brain Mapp. 2026 Aug;47(11):e70622. doi: 10.1002/hbm.70622.

ABSTRACT

Graph theory provides a promising technique to investigate Alzheimer's disease (AD)-related alterations in brain network properties. However, there are discrepancies in the reported disruptions that occur to network topology across the AD continuum. In this study, we examined whether diagnostic group differences in graph metrics are attributed to differences in denoising approach used in fMRI processing. Resting state data from 60 cognitively normal (CN), 55 Mild Cognitive Impairment (MCI), and 38 AD participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were denoised using 11 pipelines including combinations of confound regression (head motion parameters, white matter [WM], cerebrospinal fluid [CSF], global signal), volume censoring (scrubbing, spike regression), and component-based noise removal (Independent Component Analysis-based Automatic Removal of Motion Artifacts [ICA-AROMA], anatomical and temporal component correction). Graph metrics representing network segregation (clustering coefficient, modularity, local efficiency), network integration (largest connected component, path length, global efficiency), and small-worldness were calculated. The results revealed that diagnostic group differences in modularity and local efficiency were dependent on denoising approach, especially in high-parameter regression models in combination with censoring methods (36 parameters and spike regressor or volume censoring). Independent of denoising approach, CN exhibited more segregated (clustering coefficient) but less integrated (largest component, path length, global efficiency) networks than MCI and AD. Independent of diagnosis, denoising strategy significantly affected the magnitude of all metrics, particularly models including global signal regression. Collectively, these results suggest that the directionality of the diagnostic differences in network topology, particularly in global metrics of network segregation, can vary based upon the denoising approach employed, although the effect size is small. Transparent reporting of preprocessing decisions is critical for the accurate interpretation of graph theoretical findings in the context of AD and a better understanding of the mechanisms underlying pathological aging.

PMID:42568124 | DOI:10.1002/hbm.70622

Cogn Affect Behav Neurosci. 2026 Aug 7. doi: 10.3758/s13415-026-01482-6. Online ahead of print.

ABSTRACT

Although evidence suggests that psychosocial stress is a risk factor for cognitive decline in aging adults, potential mechanisms for this association are not well understood. This cross-sectional study examined associations of two measures of self-reported psychosocial stress, including the perceived stress scale (PSS) and a stressful life events (SLE) questionnaire, with functional connectivity in four large-scale, nonoverlapping brain networks derived from resting-state functional magnetic resonance imaging (rs-fMRI). Analyses included 426 late middle-aged and older participants from the Healthy Minds for Life study of the Precision Aging® Network (M (SD) age = 64.5 (7.8) years, 71% female, 33% from underrepresented racial/ethnic groups). Higher SLE scores were associated with lower functional connectivity in the default mode, salience/ventral attention, and dorsal attention networks. Higher SLE scores were additionally associated with lower cognitive performance. Patterns of results were similar when individuals with possible cognitive impairment were excluded. These findings indicate that higher levels of psychosocial stress, particularly stressful life events, are associated with lower connectivity in several large-scale functional brain networks and suggest one mechanism by which everyday experiences may shape the aging brain.

PMID:42568033 | DOI:10.3758/s13415-026-01482-6

Int Psychogeriatr. 2026 Aug 7:100255. doi: 10.1016/j.inpsyc.2026.100255. Online ahead of print.

ABSTRACT

OBJECTIVES: This study explored whether distinct Alzheimer's disease (AD) structural atrophy subtypes exhibit divergent functional profiles.

DESIGN: A cross-sectional multimodal neuroimaging and electrophysiological study.

SETTING: Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

PARTICIPANTS: A total of 116 patients with AD and 74 cognitively unimpaired controls underwent structural MRI. Patients with AD were stratified into three MRI-derived atrophy-pattern groups corresponding to hippocampal-sparing (HpSp-MRI), typical (tAD-MRI), and limbic-predominant (LP-MRI) subtypes.

MEASUREMENTS: Resting-state functional MRI was used to assess intra- and internetwork functional connectivity, and EEG was used to evaluate spectral power and microstate dynamics.

RESULTS: The HpSp-MRI subtype showed lower intranetwork connectivity than both the LP-MRI and tAD-MRI subtypes in the visual, somatomotor, and dorsal attention networks. The LP-MRI and tAD-MRI subtypes differed in ventral attention network connectivity. Moreover, the LP-MRI subtype exhibited stronger internetwork connectivity in specific network pairs compared with the other subtypes. EEG analysis suggested a possible difference in the microstate 3-to-1 transition between the LP-MRI and tAD-MRI groups.

CONCLUSIONS: MRI-derived atrophy-pattern subtypes showed different resting-state functional connectivity profiles, providing a potential basis for personalized brain network-targeted interventions in AD.

PMID:42567790 | DOI:10.1016/j.inpsyc.2026.100255

Neuroscience. 2026 Aug 7:S0306-4522(26)00532-4. doi: 10.1016/j.neuroscience.2026.08.003. Online ahead of print.

ABSTRACT

BACKGROUND: Primary angle-closure glaucoma (PACG) damages retinal ganglion cells (RGCs) and is associated with neurodegeneration. This study used resting-state functional magnetic resonance imaging (fMRI) to analyze hemispheric lateralization and cooperative functional alterations in PACG. Machine learning assessed the classification efficacy of neuroimaging indicators, while integrated transcriptomics described spatial relationships between neuroimaging changes and genes, neurotransmitters, and cell types.

METHODS: Resting-state fMRI data were collected from 101 subjects (44 patients with PACG and 57 controls). Whole-brain maps of the Autonomy Index and connectivity of functional homotopic voxels (CFH) were constructed. Their classification efficacy was assessed using five machine learning classifiers. Partial Least Squares (PLS) spatial correlation analysis examined relationships between neuroimaging maps and gene-transcript profiles, cell type density, and neurotransmitter-receptor distribution maps.

RESULTS: PACG showed increased Autonomy Index in cerebellar Crus II and the right paracentral lobule, with widespread reductions in interhemispheric cooperation. Five machine learning models yielded classification results. Image-transcriptome analysis showed that positive Autonomy Index and CFH-positive gene features were enriched in synaptic signaling and neurodevelopment, whereas negative Autonomy Index and CFH-negative gene profiles correlated with neurodegeneration, metabolic dysfunction, and vascular-immune responses. Oligodendrocytes and endothelial cells showed spatial associations with the Autonomy Index and CFH. Brain lateralization and interhemispheric cooperation showed spatial correlations with VAChT topology and several neurotransmitter receptor/transporter maps.

CONCLUSION: PACG is characterized by enhanced cerebral lateralization and diminished interhemispheric cooperation. Explainable machine learning evaluated the classification efficacy of these imaging features. These findings provide a multimodal spatial-association framework relating PACG-related imaging alterations to normative molecular and cellular brain maps.

PMID:42567471 | DOI:10.1016/j.neuroscience.2026.08.003

Neuroimage. 2026 Aug 7:122160. doi: 10.1016/j.neuroimage.2026.122160. Online ahead of print.

ABSTRACT

Functional magnetic resonance imaging (fMRI) is the most commonly used technique for non-invasive exploration of human cognition and neuroscience. Conventional T2*-weighted single-echo resting-state fMRI (SE-rfMRI) is limited by signal loss in regions prone to susceptibility artifacts and inseparable confounding from non-neuronal baseline (i.e., initial signal intensity S0) fluctuations. While multi-echo optimally combined rfMRI (ME-OC) effectively mitigates signal loss, confounding from S0 fluctuations remains unaddressed. Here, we leverage quantitative T2* fluctuation from ME-rfMRI to derive intrinsic functional metrics that are biophysically cleaner and more robust. Across both cortical and subcortical brain regions, we systematically evaluated the test-retest reliability and functional validity of two key local metrics, amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), derived from our proposed method against those from conventional SE-rfMRI and ME-OC. In subcortical regions, T2*-derived metrics showed the highest mean ICCs among the three signal representations for both ALFF (ICC = 0.67, 0.66, and 0.54) and ReHo (ICC = 0.73, 0.67, and 0.63) for T2* fluctuation, ME-OC, and SE-rfMRI, respectively. A similar regionally selective pattern was observed in cortical areas susceptible to magnetic field inhomogeneities, including the orbitofrontal cortex (ALFF ICC = 0.87, 0.75, and 0.82), insula (0.83, 0.61, and 0.71), and temporal pole (0.80, 0.73, and 0.79) for T2* fluctuation, ME-OC, and SE-rfMRI, respectively. In terms of functional validity, ALFF from T2* fluctuation uniquely revealed significant condition-related differences in the right putamen, inferior frontal gyrus, and suborbital sulcus, which both ME-OC and SE-rfMRI failed to detect. Together, our findings suggest that quantitative T2*-derived metrics may provide a reliable and more biophysically specific characterization of intrinsic fMRI signal fluctuations, particularly in subcortical and susceptibility-prone cortical regions, and may complement conventional approaches in future research applications.

PMID:42567430 | DOI:10.1016/j.neuroimage.2026.122160

Brain. 2026 Aug 7:awag272. doi: 10.1093/brain/awag272. Online ahead of print.

ABSTRACT

The precise neuromodulatory mechanisms underlying consciousness and its disorders, despite growing evidence in both animals and humans, remain poorly understood at the subcortical level. The basal ganglia, a key component of the cortico-basal ganglia-thalamo-cortical loop, are known to play a crucial role in mediating consciousness and behavioural responsiveness to the environment. Here, we aimed to present a comprehensive mapping of the distinct contributions of basal ganglia nuclei and their associated neurotransmitter systems in pharmacologically induced and pathological loss of responsiveness. We used functional MRI to provide a systematic investigation of 9 major nuclei (putamen, caudate, nucleus accumbens, globus pallidus external, globus pallidus internal, substantia nigra pars compacta, substantia nigra pars reticulata, ventral pallidus, and subthalamic nucleus) and their functional relationship with 19 major neurotransmitter systems in loss of responsiveness, in both healthy volunteers under propofol anaesthesia (n = 16) and patients with disorders of consciousness (DOC) (i.e. minimally conscious, unresponsive wakefulness syndrome) (n = 22). We found that in pharmacologically-induced loss of responsiveness, the functional connectivity changes of the putamen (Pu) correlated with the norepinephrine transporter (NET), and the globus pallidus external (GPe) with the serotonin transporter (5-HTT) and vesicular acetylcholine transporter (VAChT); additionally, altered connectivity in the ventral pallidum (VeP) was associated with the norepinephrine transporter (NET). In contrast, with pathological-induced loss of responsiveness, we found that connectivity changes of the caudate were associated with the serotonin transporter (5-HTT), dopamine transporter (DAT), and GABAA receptor, and connectivity changes of the substantia nigra pars compacta (SNc) were associated with the cannabinoid (CB1) receptor. Finally, we report that among all basal ganglia nuclei, a key dopamine-rich area of the basal ganglia-the substantia nigra-was found to have the largest DOC subgroup difference in functional connectivity, following stratification based on mental-imagery task responsiveness. Critically, we provide evidence that pharmacological and pathological loss of responsiveness involve distinct neurotransmitter system contributions across individual basal ganglia nuclei, offering a novel framework for targeted therapeutic interventions in patients with disorders of consciousness.

PMID:42565506 | DOI:10.1093/brain/awag272

Ann Child Neurol Soc. 2024 Jul 11;2(3):225-234. doi: 10.1002/cns3.20077. eCollection 2024 Sep.

ABSTRACT

OBJECTIVE: The Child Neurology Society 2023 Annual Meeting Neurocritical Care Special Interest Group discussed pediatric opioid use-associated neurotoxicity with cerebellar edema (POUNCE). Inspired by the discussion and the suspicion of an underrecognized severe form of the disorder, we provide a case series and literature review on this important and emerging topic.

METHODS: The meeting was moderated by coauthor DSM, with formal presentation by coauthor AG, and supplemented with a supporting case by coauthor VLB. The attendees, by show of hand, were queried for experience with direct care of children in the critical care unit with neurotoxicity from opioid exposure. These meeting elements informed our literature review and case series.

RESULTS: A key focus of the meeting was the importance of interdisciplinary communication regarding POUNCE, emphasizing the necessity for neurosurgical assessment due to mass effect. Approximately 10 of 40 attendees, representing different US hospitals, reported caring for children with opioid neurotoxicity and concern for increased intracranial pressure. Described during the meeting was a 2-year-old girl with opioid exposure, rapidly worsening neurological exam, and transforaminal herniation concerning for severe POUNCE syndrome and impact on brain networks by resting-state functional magnetic resonanance imaging (rs-MRI). After surgical decompression did not improve her neurological function, she underwent rs-MRI, electroencephalogram, and MRI. The networks indicated better neurological function than the exam, consistent with outcome. In contrast, the second patient, was an 11-month-old boy with fentanyl exposure who was treated for opioid overdose and closely monitored clinically. He did not require surgical intervention and has recovered well.

INTERPRETATION: These patients add to the few publications documenting the management of POUNCE, which may require urgent posterior cranial fossa decompression, and highlight the potential for good outcomes. Additionally, this is the first report documenting rs-fMRI for this condition, which was consistent with the patient's outcome.

PMID:42563936 | PMC:PMC13359337 | DOI:10.1002/cns3.20077

J Neurotrauma. 2026 Aug 7:8977151261474842. doi: 10.1177/08977151261474842. Online ahead of print.

ABSTRACT

Repetitive, nonconcussive head impacts in collision sports are associated with lasting neurophysiological effects. This study investigates region-specific changes in neocortical mean diffusivity (MD) and resting-state functional magnetic resonance imaging (fMRI) power spectral density (fMRI-PSD) that correlate with cumulative nonconcussive linear risk-weighted exposure (RWE-Lin) sustained over one high school football season. Pre- to postseason percent changes in MD (%ΔMD) and fMRI-PSD (%ΔfMRI-PSD) were calculated for football players without diagnosed concussions during the season of observation (n = 87 player-seasons). Voxelwise linear regression analyses examined relationships between RWE-Lin with neocortical %ΔMD and %ΔfMRI-PSD. False discovery rate-corrected alpha thresholds of 0.0125 accounted for multiple comparisons and directionality within each test. While controlling for age, body mass index, days between scans, position group (skill vs. line), level (junior varsity vs. varsity), and concussion history, RWE-Lin was significantly positively correlated with %ΔMD (p = 1.12 × 10-5) and inversely correlated with %ΔfMRI-PSD in the frontal cortex (p = 7.36 × 10-4). Football players were stratified into high RWE-Lin (n = 13) and low RWE-Lin (n = 37) groups using the Jenks natural breaks algorithm. Noncollision athletes (NCAs, n = 11) served as external controls. When comparing imaging measures across the three groups, the high RWE-Lin football group showed significant differences from both NCA and low RWE-Lin football groups in frontal %ΔMD and %ΔfMRI-PSD (p < 0.05). No significant imaging differences were observed between NCA and low RWE-Lin football groups. Biomechanical modeling localized high-risk impact regions that have high spatial correspondence to the observed imaging abnormalities. Exploratory post hoc voxelwise analyses of magnetoencephalography spectral power detected no significant voxelwise associations with RWE-Lin. In the absence of diagnosed concussion, high-impact football players exhibit abnormal structural and neurovascular changes in the frontal cortex. These regions overlap with those identified to be at greatest risk from biomechanical modeling and those implicated in the pathogenesis of chronic traumatic encephalopathy. Importantly, these imaging abnormalities were not generally observed in football players with lower RWE-Lin. These findings suggest that limiting the number and severity of head impacts may be an effective strategy to mitigate subclinical brain injury in American football.

PMID:42563522 | DOI:10.1177/08977151261474842

BMC Neurol. 2026 Jul 27;26(1):501. doi: 10.1186/s12883-025-04605-7.

ABSTRACT

BACKGROUND: To recover lower-limb motor function is a primary goal for rehabilitation after anterior cruciate ligament (ACL) reconstruction. Although quantitative testing and questionnaire evaluation provide a lot of valuable information, functional magnetic resonance imaging (fMRI) provides a powerful method to preliminarily explore the neural recovery process of novel rehabilitation interventions. In this case, we aimed to investigate changes in functional connectivity (FC) of motor imagery-based brain-computer interface (MI-BCI) combined with tDCS intervention in early post-ACL reconstruction rehabilitation, monitored via resting-state fMRI.

CASE PRESENTATION: A 38-year-old man patient who underwent left ACL reconstruction received MI-BCI combined with tDCS intervention 5sessions/peek for 4 weeks. before and after the intervention, the resting-state fMRI was assessed. Seed-based analysis was performed using the primary motor cortex (M1) and supplementary motor area (SMA) as the seeds, representing the sensorimotor network (SMN). The results showed increased connectivity between the SMN and specific motor-related (e.g., precentral gyrus, postcentral gyrus, pallidum and paracentral lobule) and sensory information processing areas (e.g., calcarine, lingual gyrus, calcarine, thalamus, posterior cingulum). In addition, decreased FC between both M1 and the bilateral precentral gyrus was observed, and the FC between the left M1, SMA, and the right frontal midline regions was also reduced.

CONCLUSIONS: Our preliminary results showed that MI-BCI combined with tDCS could be an effective method to recovery the lower-limb motor function and promote neural remodeling of an ACL reconstruction patient in early stage. Alterations of the SMN functional connectivity after intervention seems to partially explain the neural remodeling process, if applied on a large sample sizes, could provide more information about specific motor area.

PMID:42563155 | DOI:10.1186/s12883-025-04605-7

J Orthop Sci. 2026 Aug 6:S0949-2658(26)00220-4. doi: 10.1016/j.jos.2026.07.009. Online ahead of print.

ABSTRACT

OBJECTIVE: Intradiscal condoliase injection is an established minimally invasive treatment for symptomatic lumbar disc herniation (LDH), but its effects on central neural processing remain poorly understood. This study investigated longitudinal alterations in resting-state functional connectivity (rsFC) following condoliase injection and their associations with pain improvement.

METHODS: Twenty-six patients with LDH who achieved clinically meaningful pain reduction (≥50% reduction on the Visual Analogue Scale) underwent longitudinal resting-state fMRI. Seed-to-voxel analyses identified rsFC alterations between pre-treatment and 3 months post-treatment, focusing on the salience network (SN). Associations between functional connectivity changes (ΔFC) and pain improvement rates were evaluated using Spearman's rank correlation coefficients with Benjamini-Hochberg false discovery rate (FDR) correction across identified regions of interest (ROIs).

RESULTS: Condoliase treatment significantly altered SN-related cerebellar and temporoparietal pathways. Specifically, connectivity decreased between the anterior insula (AI) and a brainstem/Vermis X cluster, while it increased between the supramarginal gyrus (SMG) and temporal occipital fusiform cortex (TOFC). Pain improvement rates correlated with ΔFC in the AI-Vermis X (ρ = 0.47, p = 0.015) and SMG-TOFC (ρ = -0.48, p = 0.014) pathways. Both remained significant after FDR correction (q = 0.045).

CONCLUSIONS: Pain improvement following condoliase injection is accompanied by longitudinal reorganization of SN-related functional connectivity, highlighting salience-cerebellar and salience-temporoparietal brain plasticity during recovery from LDH.

PMID:42562727 | DOI:10.1016/j.jos.2026.07.009

Addict Behav. 2026 Aug 3;183:108825. doi: 10.1016/j.addbeh.2026.108825. Online ahead of print.

ABSTRACT

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics.

OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction.

METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively.

RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity.

CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

PMID:42561566 | DOI:10.1016/j.addbeh.2026.108825

J Behav Addict. 2026 Aug 6:2006.2025.00500. doi: 10.1556/2006.2025.00500. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: A variety of self-regulation interventions have shown efficacy in treating Internet Gaming Disorder (IGD), but their shared and unique neurobiological mechanisms remain unclear. This study aims to identify a common, trans-therapeutic neural signature of recovery and to delineate the specific connectivity fingerprints of five different self-regulation interventions for IGD.

METHODS: This secondary analysis pooled resting-state fMRI data from 269 individuals with IGD who participated in one of five randomized controlled trials of self-regulation-based interventions: Approach Bias Modification (ApBM), Retrieval-Aversive Conditioning (R-AC), Progressive Aerobic Training (PAT), face-to-face Mindfulness Meditation (MM), and a Digital (online) mindfulness intervention. Participants were diagnosed with IGD according to DSM-5. Partial Least Squares (PLS) regression was used to identify a shared connectivity pattern associated with clinical improvement and similarity network fusion to define intervention-specific connectivity fingerprints. Imaging-transcriptomic analysis was further used to explore the molecular correlates.

RESULTS: All interventions were associated with significant reductions in IGD severity. PLS analysis identified a shared connectivity pattern predictive of treatment response, characterized by a rebalancing of Subcortical Network (SCN) connectivity along the sensorimotor-association axis. This shared pattern was linked to gene expression profiles related to cellular stress and neuroplasticity. Each intervention also induced a unique connectivity fingerprint, targeting distinct neural circuits.

DISCUSSION AND CONCLUSIONS: Diverse self-regulation interventions for IGD converge on a shared therapeutic pathway involving the large-scale reorganization of cortico-subcortical circuits. These findings identify a robust neurobiological phenotype of recovery, offering a potential biomarker for treatment response and a target for future circuit-based therapies.

PMID:42560759 | DOI:10.1556/2006.2025.00500