Most recent paper

Neurosci Lett. 2026 Mar 18:138584. doi: 10.1016/j.neulet.2026.138584. Online ahead of print.

ABSTRACT

Reactive stepping is impaired in people with Parkinson's disease (PwPD) and can be trained through practice. However, these improvements are often variable across individuals. Identifying neurological predictors and potential mechanisms of this variability can improve the efficiency of rehabilitation. This study investigated the association between improvements in backward reactive stepping performance through training and resting-state functional magnetic resonance imaging (rs-fMRI) in PwPD. 15 PwPD underwent rs-fMRI and an eighteen-week multiple-baseline study, which included baseline assessments (B1 and B2, 2-weeks apart), a 2-week training protocol, and post-training assessments immediately after protocol (P1) and 2-months later (P2), in which we assessed anterior-posterior margin of stability (MOSAP) at first foot contact. Linear regression analyses assessed the relationship between functional connectivity, using a region of interest approach, and immediate (P1-B2) and retained (P2-B2) improvements in MOSAP during reactive stepping. Results showed that higher right thalamus-right amygdala connectivity was related to immediate MOSAP improvements (pFDR < 0.05). Right thalamus-right amygdala, left caudate-left hippocampus, and left thalamus-left hippocampus connectivity were associated with better long-term retention of MOSAP (pFDR's < 0.05). These findings suggest thalamo-limbic coupling may contribute to immediate and retained improvements in reactive balance in PwPD and could aid in identifying individuals who would benefit most from balance rehabilitation.

PMID:41862073 | DOI:10.1016/j.neulet.2026.138584

Mol Neurobiol. 2026 Mar 20;63(1):510. doi: 10.1007/s12035-026-05781-4.

ABSTRACT

Post-stroke aphasia (PSA) is a prevalent complication of left-hemispheric stroke, yet cerebellar contributions to language and cognition remain insufficiently characterized at the network level. We investigated cerebellar functional network topology in PSA and its associations with language and cognitive performance. Seventy-three right-handed PSA patients and 75 matched healthy controls underwent 3T resting-state functional magnetic resonance imaging (rs-fMRI). The cerebellum was parcellated using the Seitzman-27 atlas, which assigns cerebellar ROIs to canonical large-scale networks, allowing network-specific characterization and interpretable comparisons across functional systems. Global and nodal topological metrics and ROI-to-ROI functional connectivity were quantified, and their relationships with language and non-language cognition were assessed. Small-world organization was preserved in both groups, but PSA patients showed significant reductions in the small-world index, clustering coefficient, and local efficiency, indicating impaired network segregation and local processing. Nodal analysis revealed decreased degree centrality in the frontoparietal network and increased degree centrality in the dorsal somatomotor network. Functional connectivity was reduced within the default mode and frontoparietal networks, while connectivity between frontoparietal and dorsal somatomotor regions increased (FDR-corrected). Lower clustering coefficient and local efficiency were associated with poorer auditory comprehension, memory, and reasoning. Lesion volume was associated with worse language and cognitive outcomes but was not associated with global cerebellar network measures after covariate adjustment. These findings provide novel network-level evidence of altered cerebellar topology in PSA, extending prior cortical-focused models. The results suggest that cerebellar network disruption is associated with language and cognitive deficits and may inform the development of network-based imaging markers and motivate future longitudinal and intervention studies in aphasia.

PMID:41860713 | DOI:10.1007/s12035-026-05781-4

Front Aging Neurosci. 2026 Mar 4;18:1746491. doi: 10.3389/fnagi.2026.1746491. eCollection 2026.

ABSTRACT

BACKGROUND: Parkinson's disease (PD) entails widespread neurodegenerative changes extending beyond motor symptoms to cognitive and large-scale network alterations that compromise functional autonomy. Financial abilities (FAs) are complex, ecologically relevant skills crucial for independent living, yet their neurocognitive and neurofunctional substrates in PD remain largely unexplored. This study investigates the cognitive, structural, and neurofunctional correlates of basic and advanced FAs in PD with mild cognitive impairment (PD-MCI), using voxel-based morphometry to identify structural brain changes associated with FAs and resting-state network analyses to elucidate how brain connectivity supports preserved financial functioning.

METHODS: Thirty three individuals with PD-MCI completed a comprehensive neuropsychological assessment, including the Numerical Activities of Daily Living-Financial Short battery, to evaluate basic and advanced FAs. A subset of patients (n = 24) underwent acquisition of 3T structural and resting-state functional neuroimaging data. To identify cognitive and neural predictors of basic and advanced FAs, multiple regression models incorporating demographic covariates, cognitive and neuroimaging predictors were employed via stepwise Akaike Information Criterion and LASSO procedures.

RESULTS: Basic FAs were associated with general cognition and formal numerical competence (i.e., arithmetic knowledge), alongside negative functional correlations between somatomotor and subcortical networks. Advanced FAs were associated with different cognitive functions, such as executive ones, informal numerical competencies (i.e., use of numbers in everyday life), social cognition, language, and memory, and were linked to cerebellar network dynamics, specifically, increased anti-correlation with salience and limbic systems and enhanced synchronization with frontoparietal and subcortical circuits.

DISCUSSION: FAs in PD-MCI rely on a dynamic balance between network specialization and compensatory integration, reflecting adaptive reorganization of cortico-subcortical and cerebellar systems that may sustain complex cognitive functioning and functional independence.

PMID:41858788 | PMC:PMC12995605 | DOI:10.3389/fnagi.2026.1746491

Front Toxicol. 2026 Mar 5;8:1772515. doi: 10.3389/ftox.2026.1772515. eCollection 2026.

ABSTRACT

INTRODUCTION: Potentially more than 100,000 US troops were exposed to organophosphorus (OP) nerve agents when an ammunition bunker at Khamisiyah, Iraq was destroyed shortly after the end of the 1991 Gulf War (GW). We previously reported evidence of differences in brain structure and function in GW veterans with predicted exposure to the Khamisiyah plume compared to veterans without predicted exposure. Here, we investigate the effects of predicted exposure to the Khamisiyah plume on brain functional connectivity in the default mode network (DMN).

METHODS: Forty-one GW veterans (19 with and 22 without predicted exposure) underwent structural and resting-state magnetic resonance imaging (MRI) on a 3 Tesla scanner. Differences in DMN connectivity between veterans with and without predicted Khamisiyah exposure were examined using a left posterior cingulate cortex (PCC) seed-based analysis in AFNI. FreeSurfer was used to derive quantitative estimates of total hippocampal volume. The veterans were also assessed with the Conners Continuous Performance Test (CPT).

RESULTS: Compared to veterans without predicted exposure, those with predicted Khamisiyah exposure demonstrated weaker connectivity between the left PCC and a cluster in the caudal right anterior cingulate cortex (ACC). Veterans with predicted exposure also had smaller left hippocampal volume compared to unexposed veterans.

DISCUSSION: Although the cross-sectional nature of this study precludes conclusions about causality, the finding of decreased DMN functional connectivity in GW veterans with predicted Khamisiyah exposure warrants replication in a larger, independent sample. If confirmed, this result would add to the literature suggesting persistent differences in brain function between deployed GW veterans with and without predicted Khamisiyah exposure and argue for further investigation into the long-term effects of GW-deployment related exposures.

PMID:41858729 | PMC:PMC12999065 | DOI:10.3389/ftox.2026.1772515

BMC Med. 2026 Mar 19. doi: 10.1186/s12916-026-04796-x. Online ahead of print.

ABSTRACT

BACKGROUND: Subcortical structures are pivotal for cortico-subcortical communication, yet are highly vulnerable to stroke. Damage to these structures can produce widespread cortical dysfunction, but how subcortical stroke reshapes the macroscale hierarchical organization of cortical networks remains poorly understood. Clarifying this relationship is critical for understanding subcortical contributions to brain-wide communication and for identifying reliable neural markers of clinical outcome.

METHODS: We analyzed resting-state fMRI data from two independent cohorts of patients with subcortical stroke (discovery, 55 patients, 49 controls; replication, 23 patients, 26 controls). Cortical functional organization was mapped using diffusion map embedding to derive connectivity gradients, and group differences were quantified at both global and regional levels. Gradient metrics were further compared with conventional functional connectivity strength and tested for predictive utility using multivariate ridge regression against neurological outcome measures.

RESULTS: Across cohorts, patients consistently exhibited compression of the principal unimodal-to-transmodal gradient, reflecting diminished hierarchical differentiation between sensory and association cortices. These alterations were stable over the first three months of recovery and spatially aligned with normative maps of dopaminergic, GABAergic, glutamatergic, serotonergic and cannabinoid systems. By contrast, conventional functional connectivity strength metrics showed poor reproducibility. Gradient features outperformed connectivity strength in predicting overall neurological severity (NIHSS scores) and generalized robustly across cohorts, although predictive power for motor-specific deficits (FMA scores) was limited.

CONCLUSIONS: Subcortical stroke disrupts cortical functional hierarchy in a reproducible and neurochemically constrained manner, and this disruption serves as a robust biomarker of global neurological impairment. These findings establish cortical gradients as a mechanistically informative and clinically relevant tool for probing subcortical-cortical interactions, with potential to inform prognosis and targeted neurorehabilitation.

PMID:41857530 | DOI:10.1186/s12916-026-04796-x

J Neurosci Methods. 2026 Mar 17:110745. doi: 10.1016/j.jneumeth.2026.110745. Online ahead of print.

ABSTRACT

BACKGROUND: Resting-state fMRI connectivity is commonly estimated by single-value correlations that ignore run-to-run variability and sampling uncertainty, potentially obscuring subtle group effects such as sex-related differences in network stability.

NEW METHOD: We introduce a novel interval Type-II fuzzy graph framework that encodes connectivity uncertainty via block-bootstrap bounds across four HCP resting-state runs and derives stable α-cut graphs. We quantify uncertainty-aware stability using Disintegration Index (DI), Span Integrity (SI), and their composite DI×SI at both global and node-wise levels.

RESULTS: Sex differences in DI×SI were robust but depended on the parcellation scheme. Using a macro-anatomical Standard atlas (cortex + subcortex), females showed higher composite stability in the conservative-to-intermediate α regime, consistent with a more stable high-certainty cortico-subcortical backbone. In contrast, using the cortical Yeo17 functional-network atlas, males showed higher DI×SI across comparable α ranges, indicating relatively greater stability of intra-cortical functional-network organization. Node-wise effects likewise differed across atlases, highlighting subcortical hubs in the Standard representation and distributed cortical networks in Yeo17. These effects were most pronounced in the conservative low-to-intermediate α regime.

COMPARISON WITH EXISTING METHODS: A matched crisp Pearson-correlation baseline yielded substantially smaller and less stable effect sizes, showing that uncertainty-aware modeling increases sensitivity to reproducible and cross-run stable sex effects.

CONCLUSIONS: Type-II fuzzy connectomics reveals robust, α-dependent sex differences whose direction depends on atlas level, providing complementary insights into whole-brain versus cortical-network stability.

PMID:41856381 | DOI:10.1016/j.jneumeth.2026.110745

Prog Neurobiol. 2026 Mar 17:102906. doi: 10.1016/j.pneurobio.2026.102906. Online ahead of print.

ABSTRACT

Many brain diseases and disorders lack objective measures of brain function as indicators of pathology. The search for brain function biomarkers is complicated by the fact that these conditions are often heterogeneous and described as a spectrum from normal to abnormal rather than a sick-healthy dichotomy. Normative modeling addresses these challenges by characterizing the normal variation of brain function given sex and age and identifying abnormalities as deviations from this norm. Focusing on functional connectivity (FC) as a way to capture the network properties of the brain's activity, we here argue that the pathological effects of neurological or psychiatric disease lie at the systemic level, and that whole-brain normative models are more suitable to capture individual variations associated to these complex conditions than existing localized approaches that analyze one connection at a time. To be able to capture the whole-brain effects of disease, we thus propose Functional Connectivity Integrative Normative Modeling (FUNCOIN) as a novel whole-brain approach to normative modeling of FC. Using FUNCOIN and UK Biobank resting-state fMRI data from 46,000 healthy subjects across training and testing sets, we found that subjects with bipolar disorder and Parkinson's disease were significantly, and substantially, more likely than healthy subjects to exhibit abnormal FC patterns, which was not seen in localized models. Subjects with bipolar disorder divided into two distinct subgroups characterized by different brain function deviations. In Parkinson's disease subjects, abnormal FC patterns were significant even on scans up to 8 years before diagnosis.

PMID:41856310 | DOI:10.1016/j.pneurobio.2026.102906

Adv Sci (Weinh). 2026 Mar 19:e17234. doi: 10.1002/advs.202517234. Online ahead of print.

ABSTRACT

Exploring the dynamics of complex systems such as the human brain is challenging due to inherent uncertainties and the limited availability of high-quality data. Here, we develop a mathematical theory for noisy linear recurrent neural networks (lRNNs) within the reservoir computing framework and demonstrate their effectiveness in constructing autonomous in silico replicas - digital-twins - of brain activity. We show that the Laplace-transform poles of high-dimensional inferred lRNNs directly encode the spectral properties of observed systems and are linked to the kernels of auto-regressive models. Notably, our approach enables accurate recovery of the system's linear spectrum even when observations undergo conventional preprocessing, including band-pass filtering pipelines commonly used in neural recordings and resting-state fMRI. In these regimes, established techniques such as dynamic mode decomposition often produce spurious spectral estimates. Applying our framework to resting-state fMRI, we successfully predict and decompose BOLD activity into spatiotemporal modes in a low-dimensional latent state space confined around a single equilibrium point. The inferred lRNNs provide interpretable signatures that differentiate subjects and brain areas, supporting biologically meaningful clustering. This flexible digital-twin framework opens the door to virtual experiments and computationally efficient real-time adaptive learning, offering a promising avenue for personalized medicine and intervention strategies.

PMID:41855584 | DOI:10.1002/advs.202517234

J Craniofac Surg. 2026 Mar 19. doi: 10.1097/SCS.0000000000012627. Online ahead of print.

ABSTRACT

OBJECTIVE: Training activities in alpine environments, characterized by low temperatures, hypoxia, and high physical demand, predispose individuals to craniomaxillofacial (CMF) complex injuries with potential involvement of the central nervous system in the event of accidents. However, the imaging manifestations and multimodal features of brain injury within this specific environmental context remain insufficiently characterized. This study aimed to retrospectively analyze the brain injury patterns in patients with CMF injuries sustained during alpine training, utilizing multimodal magnetic resonance imaging (MRI) data from the acute phase. It further sought to explore the interrelationships among structural damage, white matter microstructural alterations, and functional brain network abnormalities, thereby providing an imaging foundation for clinical assessment and risk stratification.

METHODS: This retrospective observational imaging study enrolled patients who sustained CMF injuries during alpine training and subsequently underwent multimodal MRI. All imaging data were derived from prior clinical examinations. MRI evaluations were performed during the acute post-injury period, with a median interval from injury to MRI of 2.6 days (interquartile range: 1.8-3.4 d). Short-term clinical follow-up data during the acute hospitalization phase were available for a subset of patients, with the endpoint defined as hospital discharge or completion of acute-phase treatment. No standardized longitudinal imaging follow-up was conducted. The MRI protocol encompassed conventional T1-weighted and T2-weighted imaging, diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). Primary analysis metrics included cerebral contusion/laceration and structural injury burden, the quantity and spatial distribution of cerebral microbleeds detected by SWI, DTI-derived white matter microstructural parameters, and topological indices of structural and functional brain networks constructed through connectomics methods. Multimodal integrative analysis was used to assess the associative characteristics between structural injury, white matter microstructural changes, and brain network dysfunction.

RESULTS: The findings revealed that patients with CMF injuries from alpine training exhibited multilevel brain injury features during the acute phase, including cerebral contusions, microbleeds, and diminished white matter microstructural integrity. Microbleeds were predominantly distributed in the corpus callosum and subcortical deep white matter regions. Their burden was closely associated with reduced white matter fractional anisotropy (FA) and weakened functional network connectivity. Structural and functional connectivity analyses demonstrated a widespread reduction in global network efficiency and clustering coefficient among the injured individuals, alongside a relative enhancement of connectivity in certain frontal lobe-related networks, suggesting the presence of network reorganization and compensation during the acute phase. Multimodal analysis further indicated that, within the alpine training context, structural lesions, white matter injury, and brain network dysfunction exhibited significant coupling. The overall injury phenotype seemed more severe compared with general trauma backgrounds.

CONCLUSIONS: Craniomaxillofacial complex injuries sustained during training in alpine environments can induce environmentally sensitive, multiscale brain damage in the acute phase, manifesting as coordinated alterations in structural injury, white matter microstructural abnormalities, and brain network functional disruption. Combined multimodal MRI analysis facilitates a comprehensive delineation of the imaging phenotype associated with such injuries, enhances the detection rate of occult brain damage, and provides critical reference for the clinical assessment, risk stratification, and intervention decision-making related to alpine environment-associated brain injury.

PMID:41855108 | DOI:10.1097/SCS.0000000000012627

Front Neurosci. 2026 Mar 3;20:1797621. doi: 10.3389/fnins.2026.1797621. eCollection 2026.

ABSTRACT

[This corrects the article DOI: 10.3389/fnins.2025.1484954.].

PMID:41853676 | PMC:PMC12993821 | DOI:10.3389/fnins.2026.1797621

Biol Psychiatry Glob Open Sci. 2026 Jan 10;6(3):100689. doi: 10.1016/j.bpsgos.2026.100689. eCollection 2026 May.

ABSTRACT

BACKGROUND: Childhood disruptive behavior problems are linked to aberrant integrity within large-scale cognitive control networks. However, it is unclear whether transitory or dynamic variation in the functional brain architecture is a marker of disruptive behavior problems. In this study, we tested whether functional connectivity across dynamic networks is distinctly associated with the transdiagnostic symptom domain of disruptive behavior problems in children.

METHODS: Participants were 9 to 10-year-olds from the Adolescent Brain Cognitive Development Study who completed resting-state functional magnetic resonance imaging (fMRI) (N = 877). We used a dynamic connectivity approach leveraging a hidden semi-Markov model to identify transient properties of brain networks and states. Models estimated the time spent in each state (occupancy time) and the number of consecutive time points in a state (dwell time) for each participant. Linear regression models were utilized to identify distinct associations between dynamic properties (occupancy and sojourn times) and severity of disruptive behavior problems, while accounting for other commonly co-occurring symptoms.

RESULTS: Dynamic network markers of disruptive behavior problems included increased time in network states characterized by globally aberrant connectivity patterns in circuitry involved in cognitive control including frontoparietal and dorsal attention networks. Reliability of findings was found in a held-out sample of resting-state fMRI runs in which greater severity of disruptive behavior problems was uniquely linked to greater occupancy time in similarly characterized brain states.

CONCLUSIONS: Transdiagnostic, dynamic resting-state markers of disruptive behavior problems in youth may assist in the development of brain-based biomarkers for monitoring treatment outcomes, assessing circuit target engagement, and informing clinical decisions.

PMID:41852604 | PMC:PMC12994038 | DOI:10.1016/j.bpsgos.2026.100689

Sci Rep. 2026 Mar 18. doi: 10.1038/s41598-026-42844-x. Online ahead of print.

ABSTRACT

A cascade of biological responses to spinal cord injury (SCI), including neuroinflammation, plays a pivotal role in determining long-term outcomes and has become a primary therapeutic target. Riluzole, a neuroprotective agent, has demonstrated efficacy in preserving tissue integrity and improving motor function following SCI. The study aims to use this established treatment to verify that resting-state fMRI (rsfMRI) functional connectivity (rsFC) and TSPO PET metrics are reliable biomarkers of SCI severity, progression, and treatment response. 16 male rats with a moderate lumbar contusion injury were administered Riluzole or HBC vehicle. rsfMRI and TSPO PET scans were collected post-SCI alongside motor-sensory behavioral tests. After SCI, significantly stronger rsFC between dorsal-to-dorsal gray matter horns rostral to the SCI was observed in the riluzole group, compared to the vehicle group. A majority of horn pairs rostral and caudal to injury exhibited significant decrease in rsFC over time for both groups and correlated with post-injury behavioral deficits and recovery. TSPO-PET detected increased SCI neuroinflammatory activity. Our results demonstrate reductions in rsFC disruption, validating the role of rsFC as biomarkers of SCI severity and progression. The imaging biomarkers can be used to evaluate the responsiveness to treatment and efficacy of novel therapies in preclinical studies.

PMID:41851217 | DOI:10.1038/s41598-026-42844-x

Behav Brain Res. 2026 Mar 16:116166. doi: 10.1016/j.bbr.2026.116166. Online ahead of print.

ABSTRACT

BACKGROUND: The neurobiological mechanisms underlying individual differences in susceptibility to depression remain unclear. This study combined behavioral tests and resting-state functional magnetic resonance imaging (r-fMRI) to investigate how chronic unpredictable mild stress (CUMS) affects brain function and behavior in rats, and to identify neural markers that distinguish depression-susceptible (SUS) from resilient (RES) individuals.

METHODS: Thirty-one rats (CTRL group, n = 9; CUMS group, n = 22) underwent baseline r-fMRI scans before CUMS exposure. After 5 weeks of CUMS, behavioral tests, including sucrose preference test (SPT), forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and novel object recognition test (NORT) were conducted, followed by post-stress r-fMRI. Rats were classified into SUS and RES groups based primarily on SPT and FST performance.

RESULTS: CUMS induced depression-like behaviors in SUS rats, such as reduced sucrose preference, while RES rats remained comparable to controls. RsFC analysis revealed that SUS rats exhibited enhanced functional connectivity between the hippocampal subiculum and right hypothalamus/left hypothalamus after CUMS. Critically, at baseline, SUS rats already showed stronger left subiculum-left hypothalamic connectivity than RES rats, a difference not observed on the right side.

CONCLUSION: These findings reveal that individual susceptibility to depression is associated with distinct patterns of functional connectivity involving the hippocampal subiculum, hypothalamus, and amygdala. Critically, pre-existing hyperconnectivity between the left subiculum and left medial hypothalamus may distinguish SUS from RES rats before stress exposure. This specific neural signature may represent a potential vulnerability factor and could inform the development of biomarkers for early risk identification.

PMID:41850407 | DOI:10.1016/j.bbr.2026.116166

bioRxiv [Preprint]. 2026 Mar 6:2026.03.04.709586. doi: 10.64898/2026.03.04.709586.

ABSTRACT

Obsessive-compulsive disorder (OCD) is a disabling condition that is characterized by disruptions in distributed brain circuit dynamics. However, current network studies predominantly evaluate these circuits by measuring functional synchrony (connectivity) between pairs of regions of interest, potentially overlooking complex higher-order interactions. In this study, we applied a Hodge Laplacian topological framework to investigate these higher-order interactions in OCD. Using a large-scale resting-state fMRI dataset from the ENIGMA-OCD consortium (1,024 OCD patients and 1,028 healthy controls across 28 sites worldwide), we identified significant disruptions in topological loops spanning frontoparietal, default mode, and sensorimotor networks. Crucially, the edges constituting these abnormal loops largely lacked significant pairwise differences, highlighting higher-order multi-nodal disturbances. Subgroup analyses revealed that these disruptions were most pronounced in adult, medicated, and high-severity OCD patients. Our findings suggest that OCD pathology involves abnormal recurrent higher-order multi-region interactions, providing new insights into the brain's functional organization and offering potential biomarkers for clinical application.

PMID:41847031 | PMC:PMC12991123 | DOI:10.64898/2026.03.04.709586

bioRxiv [Preprint]. 2026 Mar 6:2026.03.04.709400. doi: 10.64898/2026.03.04.709400.

ABSTRACT

Relapse remains a major challenge in opioid addiction treatment, underscoring the need for innovative therapies. Progress in neuromodulation therapies has been limited by insufficient mechanistic understanding of stimulation engagement and disease-related changes in the brain. We used a novel, focal transcranial magnetic stimulation (TMS) system to deliver high-density theta burst stimulation (hdTBS) combined with resting-state fMRI to test whether anterior cingulate cortex (ACC) stimulation reduces relapse-like behavior and alters functional circuitry in a rodent model of opiate dependence. The coil focality and stimulation parameters approximate human TMS protocols, and the targeted region represents a functional homolog of the human ACC. We trained rats to self-administer oxycodone intravenously for 14 days. We then introduced an electric barrier for 13 days, which caused cessation of drug self-administration. We assessed relapse to oxycodone seeking immediately after training (early abstinence) and after electric-barrier exposure (late abstinence). We administered daily hdTBS or sham stimulation for 7 days before the late-abstinence test. Sham-treated rats showed a time-dependent increase in oxycodone seeking during abstinence (incubation of oxycodone craving) and reduced ACC functional connectivity. In contrast, hdTBS prevented the incubation of oxycodone craving and restored ACC connectivity with the dorsal and ventral striatum. Tracer-based axonal-projection data further showed that stimulation-induced effects aligned with regions receiving dense projections from the stimulation site, suggesting that the projection architecture is critical to the propagation of focal stimulation across distributed networks. These findings identify ACC-centered circuits as mechanistically informed targets for TMS-based interventions that aim to reduce opioid relapse during abstinence.

ONE SENTENCE SUMMARY: Prefrontal TMS stimulation reduced relapse-like behavior and restored corticostriatal circuits, highlighting translational targets for addiction treatment.

PMID:41847016 | PMC:PMC12991172 | DOI:10.64898/2026.03.04.709400

J Pain Res. 2026 Mar 12;19:592723. doi: 10.2147/JPR.S592723. eCollection 2026.

ABSTRACT

PURPOSE: This study conducted a randomized controlled trial by analyzing resting-state functional magnetic resonance imaging (rs-fMRI) data to determine the mechanisms by which Tuina alleviates pain and modulates multiple brain networks in lumbar disc herniation (LDH) patients.

PATIENTS AND METHODS: This study included 38 healthy subjects and 76 LDH patients. LDH patients were randomly assigned into the test group (TG; n = 38) and control group (CG; n = 38). TG patients received 14 days of Tuina therapy, whereas CG patients received a combination of transcutaneous electrical nerve stimulation (TENS) and lumbar traction therapy. The primary outcome measure, simplified McGill Pain Questionnaire (SF-MPQ), was used to assess pain. Pain pressure threshold (PPT), Oswestry Disability Index (ODI), Beck Depression Inventory II (BDI-II), and Beck Anxiety Inventory (BAI) were evaluated as secondary outcomes. Fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) values were evaluated from the rs-fMRI data before and after treatment.

RESULTS: The SF-MPQ score significantly decreased in both TG subjects [-13.00 (-19.00, -9.00); P <0.001] and CG subjects [-11.00 (-14.00, -7.00); P <0.001]. SF-MPQ scores were significantly different between the two groups (P <0.05). In TG subjects, Tuina inhibited spontaneous neural activity in the bilateral inferior frontal gyrus triangular part (IFGtri) and suppressed the interaction between IFGtri and other brain regions. Changes in FC between IFGtri.R and STG.pole.R positively correlated with improvements in SF-MPQ scores (r = 0.511, P = 0.005). Changes in FC between IFGtri.L and IFGtri.R negatively correlated with reduced PPT of the bilateral gluteus maximus (r = -0.518, P = 0.004).

CONCLUSION: Tuina effectively alleviates pain, lumbar dysfunction, and negative emotions in LDH patients by regulating the interactions between multiple neural networks in the brain, especially through the inferior frontal gyrus triangle area.

PMID:41846592 | PMC:PMC12990911 | DOI:10.2147/JPR.S592723

BMC Med. 2026 Mar 17. doi: 10.1186/s12916-026-04760-9. Online ahead of print.

ABSTRACT

BACKGROUND: Pain in knee osteoarthritis (KOA) involves maladaptive neuroplastic adaptations within the pain matrix. Tai Chi and transcranial direct current stimulation (tDCS) each alleviate KOA pain, potentially by modulating the dorsolateral prefrontal cortex (DLPFC). Whether combining them yields superior analgesic and neuromodulatory effects remains to be established.

METHODS: In this four-arm, parallel-group randomized controlled trial, 152 participants with KOA were allocated to a 12-week intervention: (1) Tai Chi combined with tDCS, (2) Tai Chi, (3) tDCS, or (4) a Health Education Control group. The primary outcome was pain intensity assessed using the Pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included the WOMAC Stiffness and Physical Function subscales, Visual Analogue Scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), Timed Up and Go Test (TUGT), and the 36-Item Short Form Health Survey (SF-36). Resting-state functional connectivity (rsFC) between the right DLPFC and key regions of the pain matrix was analyzed using functional magnetic resonance imaging (fMRI). Assessments were conducted at baseline and post-intervention.

RESULTS: The Tai Chi combined with tDCS group demonstrated a significantly greater reduction in WOMAC Pain subscores compared to the Health Education Control group (P < 0.001), the tDCS group (P = 0.003), and the Tai Chi group (P = 0.048). However, the combined intervention did not show statistically superior improvement over Tai Chi group in secondary outcomes. Neuroimaging results indicated that all active interventions decreased rsFC between the right DLPFC and several pain-matrix regions, including the left posterior cingulate cortex, bilateral thalamus, left precuneus, and left superior frontal gyrus. Furthermore, the extent of pain reduction was positively correlated with decreased connectivity between the right DLPFC and both the left posterior cingulate cortex and the left precuneus.

CONCLUSIONS: This exploratory trial suggests that combining Tai Chi with tDCS provides superior pain relief compared to either monotherapy in individuals with KOA. Post hoc exploratory neuroimaging analyses further indicate that this analgesic effect may be associated with changes in rsFC between the right DLPFC and regions of the pain matrix.

TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (ChiCTR2100047287).

PMID:41845339 | DOI:10.1186/s12916-026-04760-9

Transl Psychiatry. 2026 Mar 17. doi: 10.1038/s41398-026-03957-z. Online ahead of print.

ABSTRACT

Identifying reliable biomarkers of treatment response is central to advancing personalized psychiatry. While whole-brain functional connectivity models have shown promise in predicting clinical outcomes, especially for broad-spectrum interventions like cognitive-behavioral therapy, targeted treatments may benefit from more specific neuromarkers. In social anxiety disorder (SAD), Gaze-Contingent Music Reward Therapy (GC-MRT) is a novel attention bias modification (ABM) intervention designed to reduce preferential attentional allocation to socially threatening stimuli. Given the dorsal attention network's (DAN) key role in top-down attentional control, we tested whether resting-state intra-network DAN connectivity could serve as a neural predictor of response to GC-MRT. Participants with SAD were randomized to either receive GC-MRT (n = 22) or to a waitlist control condition (n = 24). Resting-state fMRI data were collected before and after the intervention. Intra-DAN connectivity at baseline and post-treatment were associated with post-treatment symptom severity in the GC-MRT group. Post-treatment intra-DAN connectivity significantly differed in the GC-MRT group relative to controls. These findings suggest that intra-network connectivity within the DAN may have the potential to function both as a predictive biomarker and as a neural marker of successful intervention. Our findings highlight the role of the DAN in attention-based clinical interventions and show that network-specific connectivity metrics may offer a more precise understanding of how targeted neuromodulation affects symptom change in SAD.

PMID:41844594 | DOI:10.1038/s41398-026-03957-z

Eur J Psychotraumatol. 2026 Dec;17(1):2636453. doi: 10.1080/20008066.2026.2636453. Epub 2026 Mar 17.

ABSTRACT

Background: Frontline healthcare workers (HCWs) experience unique patterns of repeated, chronic, and unpredictable traumatic event exposure, coupled with physiologic stress in the setting of shift-work circadian rhythm disruption, contributing to high rates of post-traumatic stress syndromes (PTSS) and substantial workforce and economic burden. The neurobiology underlying HCW-specific risk remains incompletely understood.Objective: To synthesise epidemiological, neuroimaging, physiological, and interventional evidence into a mechanistic model of HCW PTSS and to identify priorities for biomarker-guided prevention and care.Method: Literature for this narrative review was identified through a comprehensive search of peer-reviewed articles in PubMed, PsycINFO, and Google Scholar up to May 2025. Studies were included if they addressed (1) the epidemiology of PTSD in healthcare settings, (2) risk and protective factors specific to occupational trauma exposure, (3) neural, physiological, or molecular mechanisms associated with stress-related disorders in trauma-exposed personnel, or (4) interventions targeting PTSD/PTSS in HCWs and first responder populations.Results: Across studies, PTSS prevalence among HCWs is variable (≈15-74%). Repeated, chronic, and unpredictable occupational trauma, exacerbated by circadian disruption, appears to destabilise frontal-limbic circuits and systemic stress pathways, culminating in allostatic overload. Converging data suggest that multimodal biomarkers, including resting-state and task-evoked fMRI metrics, MR spectroscopy, heart rate variability, sleep architecture, cortisol and inflammatory indices can identify prodromal dysregulation and define risk stratification.Conclusions: Longitudinal, multimodal cohort designs are critically needed to track trajectories and evaluate neuroscientifically-informed treatment modalities for PTSS in this population. Framing HCW PTSS as an occupational neurobiological injury highlights the need to identify and prevent functional decline. A biomarker-guided strategy that links brain-circuit measures with autonomic, sleep, and molecular indices may offer a path to earlier identification, precision interventions, and improved outcomes for a critically at-need population that is essential to our workforce.

PMID:41841360 | DOI:10.1080/20008066.2026.2636453

BMC Complement Med Ther. 2026 Mar 16. doi: 10.1186/s12906-026-05343-0. Online ahead of print.

NO ABSTRACT

PMID:41840560 | DOI:10.1186/s12906-026-05343-0