Brain Sciences最新文献

Background: Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA occurring decades after neurosurgical procedures involving cadaveric dural grafts. While typically associated with recurrent lobar intracerebral hemorrhages, recent reports suggest a possible overlap with CAA-related inflammation (CAAri). We report a case of iCAA with features indicative of active neuroinflammation that demonstrated a positive response to immunosuppressive therapy.

Methods: Over a 12-year natural history, the patient underwent a comprehensive work-up, including serial clinical assessments, brain MRIs, core CSF biomarker analysis, amyloid PET imaging, and next-generation sequencing panel testing.

Results: Previous clinical charts confirmed the use of cadaveric graft (Lyodura) in a neurosurgical intervention thirty years before. During hospitalization for seizures, brain MRI revealed, along with a severe form of CAA, an area of vasogenic edema. Given the suspicion of an active inflammatory process, corticosteroid and subsequent methotrexate maintenance therapy were introduced, leading to clinical and radiological improvement. Over 30 months of follow-up, the patient has remained clinically and radiologically stable, with no new hemorrhagic or inflammatory events.

Conclusions: This case highlights the potential interplay between iCAA and neuroinflammation. The absence of new hemorrhages following immunosuppression suggests a possible disease-modifying effect, warranting further investigation into the role of neuroinflammation in iCAA and its therapeutic implications.

Background/Objective: This study aimed to adapt the Mental Fatigue Scale (MFs) to evaluate the psychometric properties in adult and adolescent athletes. Methods: A total of 491 adolescent and adult athletes (n = 491) consisting of 204 adults (men = 115; female = 90; age = 24.38 ± 3.18 year) and 287 adolescents (men = 178; female = 109; age = 14.97 ± 1.55 year) who actively participated in various sports branches voluntarily participated in this study. The MFs consists of fifteen (15) items and a single-factor structure and is a measurement tool used to measure the general mental fatigue level of athletes. Two experts used a four-point Likert scale to assess the content validity of each of the fifteen MFs items, which were aligned with the provided definition of mental fatigue in a sports context. Drawing on these findings, a confirmatory factor analysis was conducted on the survey data collected to assess the construct validity of this measure. Results: The outcomes of the confirmatory factor analysis provided acceptable support for factorial validity (χ²/sd = 1.52; p < 0.01, SRMR = 0.05, RMSEA = 0.08, GFI = 0.94, CFI = 0.89, NNFI = 0.87). Additionally, multi-group confirmatory factor analysis supported measurement invariance, indicating that the scale functions equivalently across adolescent and adult athletes. Furthermore, the analysis demonstrated favorable internal consistency (α = 0.88), confirming the reliability of the MFs. Test-retest after two weeks revealed an intra-class correlation of 0.90. Conclusions: Collectively, these results suggest that the MFs is a dependable and valid instrument that is particularly valuable for gauging overall mental fatigue in athletes. Coaches and sports scientists can use this assessment tool to evaluate athletes' general mental fatigue effectively.

Background: Survivors of severe traumatic brain injury (TBI) show highly heterogeneous recovery but early functional trajectories across rehabilitation, and their relationship with 1-year outcomes remain poorly characterized. Methods: We performed a secondary analysis of the Traumatic Brain Injury Model Systems (TBIMS) National Database. Adults with severe TBI (Glasgow Coma Scale ≤ 8, post-traumatic amnesia (PTA) > 7 days, or neurosurgical intervention) who received inpatient rehabilitation with Functional Independence Measure (FIM) admission and discharge totals and 1-year Glasgow Outcome Scale-Extended (GOS-E) were included (n = 9438). K-means clustering on FIM admission, FIM discharge, and 1-year GOS-E identified early functional recovery trajectories. Multinomial logistic regression related trajectory class to age, sex, PTA duration, rehabilitation length of stay (LOS), and total LOS. Logistic regression examined associations between trajectory class and 1-year home residence and rehospitalization, adjusted for age and sex. Results: Three trajectories emerged: low-functioning/limited improvers (28.0%), substantial improvers (33.7%), and high-functioning (38.3%). The low-functioning trajectory showed lower FIM scores at admission and discharge and worse 1-year GOS-E than the other trajectories. In adjusted models, older age, longer PTA, and longer LOS were associated with less favorable trajectories overall, particularly reducing the likelihood of belonging to the high-functioning trajectory. Substantial improvers and high-functioning patients had higher odds of living at home and lower odds of rehospitalization at 1 year than low-functioning patients. Conclusions: Simple routine measures can yield interpretable recovery trajectories after severe TBI that may support prognosis, discharge planning, and follow-up; these trajectories should be interpreted as population-level probabilities rather than deterministic predictions for individual patients.

Background: Commercial cognitive training programs are widely marketed as tools for enhancing cognitive performance, yet training-related task-related brain activation changes remain incompletely characterized. This preregistered meta-analysis aimed to synthesize evidence on whether commercially available cognitive training is associated with improvements in cognitive function and convergent alterations in task-related brain activation, and to explore factors that may moderate these effects. Methods: A multivariate meta-analysis was conducted on behavioral outcomes to estimate the overall effect of training on cognitive performance. Task-based neuroimaging findings were synthesized using a coordinate-based neuroimaging meta-analysis to identify consistent activation changes associated with training. Exploratory analyses examined whether participant characteristics and training parameters were associated with training-related activation changes and whether these changes were related to cognitive improvement. Results: Commercial cognitive training was associated with a significant moderate improvement in cognitive performance (Hedges' g = 0.485; 95% CI = 0.149-0.821; t = 2.924; p = 0.006). Neuroimaging analyses revealed increased activation in the left anterior cingulate cortex (L.ACC), right inferior frontal gyrus (R.IFG) and right superior temporal gyrus (R.STG), together with decreased activation in the right supplementary motor area (R.SMA). In exploratory analyses, training frequency, compliance and age were associated with differences in training-related brain activation. Activation within the L.ACC and R.IFG was significantly related to cognitive improvement. Conclusions: Commercial cognitive training was associated with cognitive gains and convergent task-related activation differences across studies. These findings provide the first quantitative neuroimaging synthesis of commercial cognitive training and highlight training frequency, compliance and age as potential moderators of training-related neural outcomes.

Background/Objectives: Children with Down Syndrome (DS) exhibit difficulties in maintaining balance and coordination in addition to limitations in functional mobility. The Cognitive-Motor Dual-Task Exercise Program (CMDT) has shown the ability to improve balance and functional mobility. This study aimed to compare the effect of CMDT versus exergaming on the balance and functional mobility of children with Down Syndrome aged 8-14 years. Methods: A randomized comparative trial was conducted, dividing participants' children with DS into two intervention groups: CMDT group and exergaming group. Participants were recruited using convenience sampling methods from the Voice of Down Syndrome Association and the Down Syndrome Charitable Association in Riyadh, Saudi Arabia. Both interventions were implemented over a period of six weeks. Outcome measures included the Timed Up and Go (TUG), Four Square Step Test (FSST), and Pediatric Balance Scale (PBS). Results: A total of 23 children with DS participated in the study. A mixed repeated measures ANCOVA shows a significant effect of time across the two groups (p < 0.001) for TUG, FSST, and PBS, indicating improvements in balance and functional mobility. There were no significant differences between the two group interventions. Conclusions: CMDT and exergaming were equally effective in improving balance and functional mobility in children with DS. Trial Registration: Clinicaltrials.gov with ID NCT06146907.

Astrocytes are critical for maintaining brain homeostasis through metabolic support, neurotransmitter regulation, and blood-brain barrier integrity. In the aging brain and neurodegenerative conditions, astrocytes undergo functional and morphological changes that culminate in a state of cellular senescence. Astrocytic senescence-characterized by irreversible cell-cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP)-is emerging as a key contributor of chronic neuroinflammation and synaptic dysfunction in aging. This review examines the molecular mechanisms underlying astrocyte senescence, highlighting how persistent DNA damage responses (DDR), oxidative stress, and mitochondrial dysfunction disrupt essential astrocytic functions (e.g., glutamate uptake, K⁺ buffering, and metabolic coupling with neurons). These senescent changes in astrocytes lead to impaired synaptic plasticity and contribute to age-related cognitive decline. Collectively, astrocytic senescence represents a pivotal and targetable mechanism in age-related neurodegeneration, and therapeutic strategies aimed at eliminating senescent cells or modulating the SASP hold promise for restoring synaptic function and promoting healthy brain aging.

Background: Sex-based variations in brain structure, hormonal balance, and neurochemistry may influence symptom presentation and recovery after mild traumatic brain injury (mTBI). This systematic review investigated sex-related differences in mTBI severity, symptoms, and recovery outcomes across different injury mechanisms. Methods: This review followed PRISMA 2020 guidelines and was registered with PROSPERO (CRD420251011379). Searches were conducted in PubMed, SPORTDiscus, Web of Science, and Scopus for articles published between 2000 and 2024. Eligible studies included adults (≥18 years) diagnosed with mTBI or concussion (Glasgow Coma Scale 13-15) with quantifiable outcome data for both sexes. Data extraction and quality assessment followed the JBI critical appraisal tools. Results: Forty-one studies involving 15,656 participants (8671 males; 6985 females) met the inclusion criteria. Female participants reported a greater symptom burden, higher pain intensity, and longer recovery times for gait abnormalities and return to activity compared with males. Neuroimaging studies showed more extensive white matter alterations in females, whereas males displayed greater reductions in cerebral blood flow. Cognitive and neurosensory outcomes revealed poorer cognitive performance, slower reaction times, and higher rates of vestibular-ocular and visual abnormalities in females. A limited number of studies explored electrophysiological measures, indicating sex-based differences in early brain responses to emotional stimuli. Conclusions: Sex plays an important role in symptom presentation and recovery after mTBI. Female patients demonstrate heightened vulnerability across several clinical domains, likely due to biological and neurochemical differences. Recognising these sex-specific patterns can support more targeted diagnostic and rehabilitation strategies. Future research should further explore the structural and biochemical mechanisms underlying these differences to improve precision in mTBI management.

Background: The rostral ventromedial medulla (RVM) is a central hub of the descending pain modulatory system, yet the inhibitory circuits that regulate its activity during neuropathic pain remain poorly defined. The zona incerta (ZI), a predominantly GABAergic nucleus in the subthalamic region, has been implicated in nociceptive modulation, but its functional connection to the RVM has not been established. Methods: A chronic constriction injury (CCI) model was used to induce neuropathic pain. Neuronal activation and circuit connectivity were examined using anatomical tracing and activity mapping. Optogenetic and chemogenetic approaches were employed to selectively manipulate ZI-derived GABAergic projections to the RVM, and mechanical sensitivity was assessed using behavioral assays. Results: CCI selectively activated ZI neurons on the ipsilateral side of nerve injury (p = 0.0452), which projected to the ipsilateral RVM. Optogenetic activation of ZI-derived terminals in the RVM significantly alleviated CCI-induced mechanical allodynia (p = 0.0038), whereas optogenetic inhibition exacerbated pain behaviors (p = 0.0183). Consistently, chemogenetic excitation of ZI-RVM neurons attenuated hypersensitivity (p < 0.0001), while chemogenetic silencing had the opposite effect (p = 0.0015). Conclusions: These findings reveal a novel diencephalic-to-brainstem inhibitory pathway that exerts dynamic control over RVM-mediated descending modulation of neuropathic pain.

Background: Sexualized substance use (SSU) describes the use of psychotropic substances in the context of sexual activity. Less is known about the role of sexualized substance use among individuals with substance use disorders (SUD) and its effect on the course of the disorder, e.g., regarding relapses after abstinence. Methods: A convenience sample of individuals undergoing SUD rehabilitation in Germany was surveyed. A questionnaire asked about SSU, sex as a risk factor for relapse, and the importance of sexuality in treatment. Results: N = 490 (30.1% female) participated; 55% of men and 63% of women reported SSU, and 56.5% of heterosexual and 82.9% of homosexual men reported SSU (p < 0.017; r = 0.20). Stimulant users are more likely to report SSU than alcohol (p < 0.001) and sedative users (p < 0.001; r = 0.296 and r = 0.261). Furthermore, 15% of women and 18% of men consider sexual activity a risk factor for relapse; homosexual men (65%) consider it significantly more often than heterosexual men (14%), while 41.2% of heterosexual women and 55% of homosexual women consider it a factor. Additionally, 27.4% of heterosexual and 69.4% identified sexuality as an important topic for therapy, while 19.8% of heterosexual women, 30% of homosexual women, 13.5% of heterosexual men, and 47.2% of homosexual men reported that sexuality had been addressed in their therapy. Conclusions: SSU was reported by individuals with a SUD who were undergoing rehabilitation treatment. Furthermore, patients consider sexual activity as a potential risk factor for relapse, with this being particularly the case for stimulant users. The topic of sexuality is highly important for patients and should, therefore, be given greater consideration in therapy in the future.

Background/Objectives: Mild cognitive impairment (MCI) affects multiple functional and cognitive domains, rendering it challenging to diagnose. Brief mental status exams are insensitive while detailed neuropsychological testing is time-consuming and presents accessibility issues. By contrast, the Oculo-Cognitive Addition Test (OCAT) is a rapid, objective tool that measures oculometric features during mental addition tasks under one minute. This study aims to develop artificial intelligence (AI)-derived predictive models using OCAT eye movement and time-based features for the early detection of those at risk for MCI, requiring more thorough assessment. Methods: The OCAT with integrated eye tracking was completed by 250 patients at the Mayo Clinic Arizona Department of Neurology. Raw gaze data analysis yielded time-related and eye movement features. Random Forest and univariate decision trees were the feature selection methods used to identify predictors of Dementia Rating Scale (DRS) outcomes. Logistic regression (LR) and K-nearest neighbors (KNN) supervised models were trained to classify PMCI using three feature sets: time-only, eye-only, and combined. Results: LR models achieved the highest performance using the combined time and eye movement features, with an accuracy of 0.97, recall of 0.91, and an AUPRC of 0.95. The eye-only and time-only LR models also performed well (accuracy = 0.93), though with slightly lower F1-scores (0.87 and 0.86, respectively). Overall, models leveraging both time and eye movement features consistently outperformed those using individual feature sets. Conclusions: Machine learning models trained on OCAT-derived features can reliably predict DRS outcomes (PASS/FAIL), offering a promising approach for early MCI identification. With further refinement, OCAT has the potential to serve as a practical and scalable cognitive screening tool, suitable for use in clinics, at the bedside, or in remote and resource-limited settings.