Restorative neurology and neuroscience最新文献

{"title":"Feasibility of a Modified Exertional Bike Test to Threshold Supervised Virtual Aerobic Exercise in Community-Dwelling Individuals with Mild Traumatic Brain Injury.","authors":"Mark C Nwakamma, Emma M Tinney, Madeleine Perko, Goretti España-Irla, Lauren Kong, Colette Chen, Jeremy Hwang, Amanda O'Brien, Ryan Luke Sodemann, Jacqueline Caefer, Julie Manczurowsky, Charles H Hillman, Alexandra Stillman, Timothy P Morris","doi":"10.1177/09226028261496160","DOIUrl":"https://doi.org/10.1177/09226028261496160","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) often creates a sequela of symptoms that complicate safely participating in aerobic exercise. Although exertional assessments have been used to evaluate exercise tolerance, data on the feasibility of using test-derived metrics to guide the intensity of aerobic exercise interventions in community-dwelling adults is yet to be presented. This secondary analysis of a wider pilot randomized control trial examined whether a modified exertional bike test (MEBT) could be used to effectively individualize supervised virtual aerobic exercise without exacerbating symptoms in individuals with a mTBI. Adults (18-55 years) diagnosed of mTBI within the previous 12 months completed the MEBT and were randomized to either a 12-week supervised virtual aerobic exercise intervention or active balance control. Those randomized to the aerobic group exercised at 65-80% of HR at MEBT-derived symptom threshold or volitional exhaustion. Descriptive session outcomes, Spearman correlations, and Fisher's z tests assessed (1) the feasibility of symptom-threshold HR intervention metrics, (2) changes in the HR-symptom relationship over time, and (3) the influence of mTBI-related confounders on HR-symptom associations. Participants completed 95.6% of aerobic sessions, with symptom exacerbation (≥3-unit increase) reported in just 3.8% of sessions. Ten of 12 participants displayed a decreased, or negative, HR-symptom severity association over time. In addition, Fisher's z tests revealed confounding variables did not meaningfully modify the HR-symptom association. Sub-symptom-thresholded exercise sessions limited symptom exacerbation, uncoupled the HR-symptom relationship, and improved exercise tolerance over time. These findings highlight the feasibility of exertional symptom-guided virtual aerobic exercise following mTBI and support progression towards larger efficacy trials.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261496160"},"PeriodicalIF":1.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Treadmill to Textbook: Neurovascular and Immune Mechanisms of Exercise-Induced Cognitive Enhancement.","authors":"Anna A Ascsillán, Zsofi Fustos, Kitti Ascsillán","doi":"10.1177/09226028261492624","DOIUrl":"https://doi.org/10.1177/09226028261492624","url":null,"abstract":"<p><p>It has been well established that physical exercise is associated with augmented cognitive function, but the exact mechanisms by which peripheral activity affects the plasticity of the brain remain mechanistically elusive. This narrative review synthesises evidence from mouse models and human studies to clarify how physical exercise may enhance hippocampus-dependent cognition through systemic, neurovascular, immune, and metabolic mechanisms instead of direct \"brain training\" alone. This distinction is supported by the limited far transfer shown in many cognitive training models, wherein improvements tend to remain task- or circuit-specific rather than reflecting general skill transfer. In rodent models, voluntary physical exercise improves learning, memory, and pattern separation, and these effects correlate with changes in hippocampal neurogenesis, synaptic plasticity, vascular remodelling, and neuroimmune state. A smaller pool of plasma-transfer studies suggests that these effects carry over between individual mice via circulating exercise-induced factors, reproducing select molecular and behavioural effects in completely sedentary recipient mice, but in humans, the causal relevance of such pathways remains unresolved. In rodent transfer experiments, exercise-conditioned blood plasma has been reported to reduce neuroinflammation and to modulate brain endothelial cells, positioning the neurovascular unit as a critical interface for peripheral-to-central nervous system communication. Beyond clusterin and Gpld1, a conceptual muscle-brain endocrine axis is emerging, where specific myokines (e.g., irisin, cathepsin B) and downstream metabolites released during physical exercise may act on vascular and immune interfaces to modulate structural plasticity. Emerging human data reinforce some of these investigated mechanisms, although causal relationships have yet to be established and remain limited. Overall, the available evidence supports a model whereby physical exercise improves cognitive function through changes in the immunometabolic environment, supporting hippocampal plasticity. These pathways may inform future studies aiming to preserve cognitive health during ageing, and the development of exercise-mimetic therapeutic strategies.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261492624"},"PeriodicalIF":1.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Intrinsic Feedback-Based Gait Training Under Visual Deprivation on Balance and Gait in Stroke Survivors: A Randomized Controlled Study.","authors":"Myunggi Cho","doi":"10.1177/09226028261495203","DOIUrl":"https://doi.org/10.1177/09226028261495203","url":null,"abstract":"<p><p>Feedback is an essential component of motor learning and rehabilitation. Although extrinsic feedback is widely used in stroke rehabilitation, excessive dependence on external cues may limit opportunities for independent movement regulation. Training that emphasizes intrinsic feedback during visual deprivation (VD) may provide individuals with greater opportunities to perceive and regulate their movements using internally available sensory information. This study investigated the effects of gait training with intrinsic feedback on balance and gait abilities in individuals with stroke compared with extrinsic feedback training and conventional physical therapy. Thirty-six individuals with stroke were randomly assigned to the gait training with intrinsic feedback (GIF) group, gait training with extrinsic feedback (GEF) group, or control group (CG). The GIF performed forward and backward linear and curvilinear gait tasks on stable and unstable surfaces during VD without continuous verbal guidance. The GEF performed the same gait tasks during VD while receiving continuous verbal guidance, whereas the CG received conventional physical therapy. All interventions were conducted for 30 min, five times per week, for 8 weeks. Outcome measures included the Four Square Step Test (FSST), weight distribution, spatiotemporal gait variables, center of pressure (COP) variables, and the 10-Meter Walk Test (10 MWT). Significant group × time interactions were observed for the FSST, weight distribution, gait velocity, cadence, paretic stance phase, paretic swing phase, paretic step time, stride time, and the 10 MWT (p < 0.05). The GIF demonstrated significantly greater improvements than both the GEF and CG in the FSST, gait velocity, cadence, paretic step time, stride time, and the 10 MWT (p < 0.05). The GIF also showed greater improvement than the CG in weight distribution (p < 0.05). These findings suggest that gait training emphasizing intrinsic feedback during VD may provide additional benefits for selected aspects of balance and gait performance in individuals with stroke.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261495203"},"PeriodicalIF":1.8,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Maintains Hippocampal Mitochondrial Function and Inhibits Neuronal Ferroptosis to Improve Diabetes-Associated Cognitive Dysfunction via Sirt1/Shh Signaling.","authors":"Ying Hu, Jiancheng Wang, Jiao Wang, Yuanyuan Deng, Wen Chen, Qin Zhang","doi":"10.1177/09226028261485654","DOIUrl":"https://doi.org/10.1177/09226028261485654","url":null,"abstract":"<p><p>BackgroundResveratrol has been shown to play a neuroprotective role in diabetic cognitive dysfunction. We determined whether resveratrol improved diabetic cognitive dysfunction through ferroptosis regulation, and explored the potential mechanism.MethodsRats were fed with a high-sucrose and high-fat diet combined with streptozotocin for establishing a diabetic model, followed by resveratrol treatment with or without erastin (a classical ferroptosis activator). Cognitive abilities were evaluated with novel object recognition test and Morris water maze test. Neuronal damage was determined using Nissl staining and Fluoro-Jade B staining. Ferroptosis-related factors such as glutathione (GSH), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) and iron (Fe²⁺) levels were evaluated. Mitochondrial function was assessed by mitochondrial morphology, mitochondrial swelling, mitochondrial membrane potential (MMP), and ATP content. Western blot was performed to measure Sirtuin 1 (Sirt1) and Sonic hedgehog (Shh) signaling pathway, and ferroptosis-related proteins. Besides, the cellular localization of Sirt1 and Shh was assessed using immunofluorescence.ResultsResveratrol ameliorated cognitive dysfunction and neuronal damage in diabetic rats and blocked hippocampal neuron ferroptosis, which were abolished by erastin. Resveratrol ameliorated hippocampal mitochondrial dysfunction (decrease of mitochondrial swelling and increases of MMP and ATP) in diabetic rats. Resveratrol treatment upregulated Sirt1 and Shh expressions in NeuN-positive neurons in the hippocampus of diabetic rats. Moreover, Shh knockdown reversed the protective effects of resveratrol on ferroptosis, cognitive dysfunction, and neuron loss.ConclusionResveratrol conferred neuroprotective effect on diabetic cognitive dysfunction by maintaining mitochondrial function and inhibiting hippocampal neuron ferroptosis via Sirt1/Shh signaling.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261485654"},"PeriodicalIF":1.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Creutzfeldt-Jakob Disease in the Era of Diagnostic Triumph and Therapeutic Defeat: A Perspective from the Bedside.","authors":"Xiaoyan Zhang, Yao Tian, Changren Li, Muyang Li, Zhenxing Wang","doi":"10.1177/09226028261488180","DOIUrl":"https://doi.org/10.1177/09226028261488180","url":null,"abstract":"<p><p>Creutzfeldt-Jakob disease (CJD) exemplifies a cruel paradox of modern neurology: we can now diagnose it with near-perfect accuracy within hours, yet we cannot alter its invariably fatal course. The advent of cerebrospinal fluid (CSF) and skin real-time quaking-induced conversion (RT-QuIC), coupled with high-specificity brain MRI, has enabled robust ante-mortem diagnostic support for CJD, which was previously only definitively established post-mortem. Yet no disease-modifying therapy exists. Drawing on a molecularly supported case of sporadic CJD, this Perspective argues that the widening gap between diagnostic precision and therapeutic impotence is not merely a failure of prion medicine-it is a stress test for the entire rare-disease ecosystem. We examine how this diagnostic triumph creates an unprecedented opportunity for presymptomatic intervention, ultra-adaptive clinical trials, and synergistic combination therapies, and we propose a strategic roadmap to ensure that the next patient diagnosed within hours has a chance, however slim, of a different outcome.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261488180"},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain Outcomes and Exercise Data from the EXERT-Stroke Pilot Clinical Trial on Post-Stroke Headaches.","authors":"Chaitali Dagli, Charity J Morgan, Keith McGregor, Chen Lin","doi":"10.1177/09226028261486597","DOIUrl":"10.1177/09226028261486597","url":null,"abstract":"<p><p>Chronic pain affects 30-50% of stroke survivors and is more complex in US veterans. This study aimed to evaluate the feasibility, safety, and preliminary effects of combined repetitive transcranial magnetic stimulation (rTMS) and aerobic exercise in veterans. We conducted a secondary analysis of the EXERT-Stroke trial, a pilot randomized, sham-controlled, double-blind study. Veterans with persistent post-stroke headache completed standardized aerobic exercise across 10 supervised sessions over 8weeks. Pain was assessed weekly via the Brief Pain Inventory (BPI) and Visual Analogue Scale (VAS). Baseline exercise capacity, blood pressure (BP), and heart rate were also measured. Linear regression examined associations between baseline physiological measures and changes in pain. Nine veterans (77.8% male, mean age 61.3 years) participated. Overall, participants experienced a mean decrease of 1.2 in pain severity and 1.0 in pain interference. Higher baseline resting and maximal systolic BP, and higher baseline resting diastolic BP, were associated with greater improvements in pain severity. Combined rTMS and aerobic exercise is feasible, safe, and may reduce post-stroke pain in veterans.This study provides preliminary support for a novel, nonpharmacologic intervention targeting chronic post-stroke pain in veterans, a population with limited treatment options and high rehabilitation needs.Trial registration: This trial was registered at clinicaltrials.gov (Registration No. [NCT04672044]) on 2020-12-11 (URL: https://clinicaltrials.gov/study/NCT04672044?cond=stroke&intr=rtms&aggFilters=docs:prot,funderType:fed,status:com,studyType:int&rank=2).</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261486597"},"PeriodicalIF":1.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purposeful Activity-Based Electrical Stimulation Improves Activities of Daily Living in Patients with Subacute Stroke and Moderate-to-Severe Upper Limb Hemiparesis: A Pilot Randomised Controlled Trial.","authors":"Seigo Minami, Yoshihiro Fukumoto, Ryuji Kobayashi, Hideaki Aoki, Takahiro Horaguchi, Kenji Takeuchi, Kengo Yoshihara, Mitsumasa Hida, Tomoki Aoyama","doi":"10.1177/09226028261481873","DOIUrl":"https://doi.org/10.1177/09226028261481873","url":null,"abstract":"<p><p>PurposeIn this randomised controlled trial study, we aimed to preliminarily evaluate the effectiveness of purposeful activity-based electrical stimulation therapy (PA-EST) in improving independence in daily living in patients with stroke and moderate-to-severe upper limb hemiparesis.MethodsThis study was conducted in the rehabilitation ward of Kyoto Ohara Memorial Hospital, Japan. Sixteen rehabilitation ward inpatients who experienced stroke and moderate-to-severe upper limb hemiparesis were included. In this randomised controlled trial, the participants were randomly assigned to either PA-EST or conventional occupational therapy (COT) and received a 2-month intervention. The primary outcome measures included motor, cognitive, and total scores on the functional independence measure (FIM). The secondary outcome measures included the Motor Activity Log (MAL), Amount of Use and Quality of Movement (QOM) subscales, and the Upper Extremity, Lower Extremity, and Total Fugl-Meyer Assessment scores.FindingsTwo-way repeated measures analysis of variance revealed significant interactions for FIM-motor (p = 0.041), FIM-total (p = 0.029), and MAL-QOM (p = 0.005), with greater improvements in the PA-EST group than in the COT group. No significant interactions were observed for the other outcome measures.ConclusionsThis randomised controlled trial study provides preliminary evidence that PA-EST may enhance activities of daily living independence in patients with subacute-phase stroke and moderate-to-severe upper limb hemiparesis. These findings support the clinical utility of PA-EST as a novel intervention strategy for advancing stroke rehabilitation.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261481873"},"PeriodicalIF":1.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complementary Visual Assessment: Validation of a High-Precision Eye-Tracking Kinetic Perimetry in the Evaluation of Visual Field Deficits in Hemianopia.","authors":"Carolina Maria Oletto, Francesco Costalunga, Eric Altieri, Cecilia Pugliese, Luca Semenzato, Sara Errigo, Davide Cantavenera, Luca Battaglini","doi":"10.1177/09226028261480542","DOIUrl":"https://doi.org/10.1177/09226028261480542","url":null,"abstract":"<p><p>Vision is a multicomponential system where different aspects of visual processing rely on distinct neural circuits. This fundamental characteristic has profound implications for how we assess visual field defects. Classical gold standard perimetry focuses primarily on contrast detection. However, the size of the scotoma could be different when measured with kinetic perimetry since motion detection relies on different neural networks. Therefore, we developed and validated a high-precision eye-tracking kinetic perimetry as a complementary tool for evaluating visual field deficits in hemianopia. We emphasized methodological transparency and precise measurement of the transition zone between sighted and blind areas. Thirty-seven participants (17 with retrochiasmal lesions and 20 healthy controls) underwent test-retest evaluation using a kinetic perimetry system integrated with a Tobii Pro Spectrum eye tracker (0.03° RMS precision, 0.3° accuracy, 600 Hz sampling rate). Results demonstrated excellent test-retest reliability with adjusted ICC values exceeding 0.90 across all conditions. The application of an algorithm (LOESS) for noise reduction further improved measurement stability, with ICC increasing to 0.996 for controls and 0.988 for patients, while reducing standard deviation of errors from 4.69° to 1.52° in the affected visual field of patients. Based on these findings, we propose that a visual field enlargement exceeding 5° can be considered a meaningful change beyond the measurement variability of our perimetry. By embracing methodological transparency, including detailed disclosure of eye-tracking specifications and error measurements, and recognizing the multicomponential nature of vision, we aim to contribute to the understanding of visual field defects and their potential for recovery.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261480542"},"PeriodicalIF":1.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Enriched Environment Components Differentially Shape the Temporal Dynamics of Anxiety-Like Behavior in Rats.","authors":"Mizuki Sudo, Yutaka Kano, Soichi Ando","doi":"10.1177/09226028261480778","DOIUrl":"https://doi.org/10.1177/09226028261480778","url":null,"abstract":"<p><p>Enriched environments (EEs) are known to improve anxiety-like and related emotional behaviors in rodents. However, EEs comprise multiple components providing distinct sensory and motor stimuli. It remains unclear how these qualitative differences in behavioral experience shape the temporal dynamics of anxiety-like and related emotional responses. Male rats were housed for 4 weeks in one of four conditions: standard environment (SE), EE with a running wheel and objects (EE), EE with a running wheel only (EER), or EE with objects only (EEO). We monitored physical activity and locomotor behaviors during the housing period. Anxiety-like behavior was evaluated using a 10-min elevated plus maze (EPM) test, which was divided into five consecutive phases to enable time-resolved analysis. Physical activity was consistently higher in the wheel-containing groups (EE and EER) than in the SE group. While rearing behavior increased in all enriched groups, object interaction time was significantly higher in the EEO group than in the EE group. In the EPM test, the EE and EER groups spent significantly more time in the open arms during the early phases (p < 0.05). Conversely, the EEO group showed greater open-arm exploration at later phases than the SE group (p = 0.0068). These findings indicate that the nature of the environmental stimuli distinctively determines the onset and progression of anxiolytic effects. Our findings demonstrate that different components of EE differentially shape the temporal profile of anxiety-like and related emotional behavior. Voluntary exercise and object-based exploration influence not only the magnitude of anxiety reduction but also the temporal trajectory of these effects. Time-resolved behavioral analysis highlights the importance of environmental quality and specific sensorymotor experiences beyond total physical activity levels.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261480778"},"PeriodicalIF":1.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Associations Between Physical Activity and Internalizing Symptoms in Early Adolescence: A Four-Wave Cross-Lagged Panel Model with Random Intercepts.","authors":"Nicole E Logan, William W Lewis-de Los Angeles","doi":"10.1177/09226028261476103","DOIUrl":"https://doi.org/10.1177/09226028261476103","url":null,"abstract":"<p><p>BackgroundRates of mental illness in adolescents are increasing at an alarming rate. At the same time, youth participation in physical activity is continually declining. International public health guidelines recommend that children spend at least 60 min/day in moderate-to-vigorous physical activity for optimal development of brain health. This study aimed to disentangle within-person effects of physical activity on mental health symptoms from stable, between-person differences using a four-wave random-intercepts cross-lagged panel model (RI-CLPM).MethodsData from the longitudinal Adolescent Brain Cognitive Development (ABCD) Study were used to follow pre-adolescent children (N = 6361) across development (10-14.2 years old). Physical activity was measured by youth-report. Internalizing and externalizing mental health behaviors were measured by the parent-reported Child Behavior Checklist. Bidirectional relationships between mental health and physical activity were assessed using RI-CLPM.ResultsFor internalizing symptoms, cross-lagged (within-person) random effects showed that higher physical activity at year 2 predicted fewer internalizing symptoms at year 3 (β= -0.037 [-0.062 to -0.012]), and from year 3 to year 4 (β = -0.045 [-0.068 to -0.022]). More internalizing symptoms at baseline predicted less physical activity from year 2 to year 3 (β = -0.076 [-0.125 to -0.027]), and from year 3 to year 4 (β = -0.075 [-0.118 to -0.031]). For externalizing symptoms, there were no significant cross-lagged or between-person effects.ConclusionIn this large, multi-wave longitudinal cohort, more physical activity was associated with fewer internalizing symptoms across early adolescent development. Additionally, higher internalizing symptoms were associated with lower physical activity across development. No associations were found with externalizing symptoms. Findings suggest that physical activity may alleviate internalizing symptoms during early adolescence, underscoring the need for promoting adherence to international physical activity guidelines in the complex management of adolescent mental health.</p>","PeriodicalId":21130,"journal":{"name":"Restorative neurology and neuroscience","volume":" ","pages":"9226028261476103"},"PeriodicalIF":1.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}