Search Results (1,609)

This commentary explores the parallel neuroanatomical and neurobiological evolution that ultimately led to modern dogs and humans, through domestication and self-domestication, respectively. The selective pressures for benignness and enhanced prosociality have reshaped brain anatomy and cognitive architecture in both Canis familiaris and Homo sapiens, leading to analogous changes including a reduction in limbic system volume and expansion of the prefrontal cortex, critical for executive control and social cognition. From a molecular point of view, shared genetic and epigenetic underpinnings of these adaptations and their implications gave rise to parallel trajectories in brain aging; notably, the emergence of canine cognitive dysfunction. Interestingly, this canine age-related cognitive decline presents significant overlaps with Alzheimer’s disease in terms of both behavioral presentation and underlying pathology. In the context of a One Health perspective, the profound influence of shared environmental exposures, such as urbanization, pollutants, and stressors, on neurodevelopment, cognitive aging, and disease susceptibility offers a compelling translational model for understanding brain health within intertwined ecological and social contexts. Full article

Background/Objectives: Frank’s sign, a diagonal earlobe crease, may reflect systemic microvascular dysfunction. We investigated whether Frank’s sign serves as a clinical marker of white matter hyperintensity (WMH) burden in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a monogenic model of pure cerebral small vessel disease. Methods: We analyzed 81 genetically confirmed CADASIL patients (61.8 ± 12.6 years, 40.7% female) and 54 age/sex-matched controls (70.3 ± 6.6 years, 48.1% female). Frank’s sign was detected using deep learning from brain MRI-reconstructed 3D facial surfaces. WMH volumes were automatically quantified and adjusted for confounders using Random Forest regression residuals. We compared Frank’s sign prevalence between groups, assessed within-CADASIL associations, and evaluated dose–response relationships across WMH tertiles. Results: Frank’s sign prevalence was significantly higher in CADASIL versus controls (66.7% vs. 42.6%, p = 0.020), with strengthened association after multivariate adjustment (OR = 4.214, 95% CI: 1.128–15.733, p = 0.032). Within CADASIL, Frank’s sign-positive patients showed 72% greater WMH burden (51.5 ± 27.1 vs. 30.0 ± 26.1 mL, p < 0.001) and lower Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) total scores (57.7 ± 19.6 vs. 71.2 ± 22.8, p = 0.006), but similar lacunes, microbleeds, and hippocampal volumes. A robust dose–response relationship emerged across WMH tertiles, with Frank’s sign prevalence increasing from 37.0% (lowest) to 74.1% (highest tertile; adjusted OR = 3.571, 95% CI: 1.134–11.253, p = 0.030). Conclusions: Frank’s sign represents an accessible biomarker of WMH burden in CADASIL, demonstrating disease-specificity and dose–response characteristics independent of vascular risk factors. The automated MRI-based detection method of Frank’s sign enables retrospective analysis of existing neuroimaging databases, transforming a bedside observation into a quantifiable neuroimaging biomarker for genetic small vessel disease stratification. Full article

Background and Objective: Cerebral cavernous malformation (CCM) is a vascular disorder causing seizures, neurological deficits, and hemorrhagic stroke. It can be sporadic or inherited via CCM1, CCM2, or CCM3 gene mutations. Inflammation is broadly recognized as a promoter of cerebral vascular malformations. This study explores inflammatory mechanisms and differences behind CCM-related hemorrhage and epilepsy. Material and Methods: The study group comprised 28 patients, ten patients with CCM-related epilepsy, and 18 patients who clinically presented with a cerebral hemorrhage at diagnosis. All patients underwent microsurgical resection of the CCMs. Formaldehyde-fixed, paraffin-embedded tissue samples were immunohistochemically stained using a monoclonal antibody against Cyclooxygenase 2 (COX-2) (Dako, Santa Clara, CA; Clone: CX-294) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) (ABCAM, Cambridge, MA, USA; ab214185). MRI and clinical data were correlated with immunohistochemical findings, and the analysis was conducted utilizing the Trainable Weka Segmentation algorithm. Results: Median CCM volume was 1.68 cm³ (IQR: 0.85–3.07 cm³). There were significantly more NLRP3-positive cells (32.56% to 91.98%; mean: 65.82%, median: 68.34%; SD: ±17.70%), compared to COX-2-positive cells (1.82% to 79.69%; mean: 45.87%, median: 49.06%; SD: ±22.56%). No correlation was shown between the volume of CCMs and a hemorrhage event (p = 0.13, 95% CI: 0.99–1.02). Symptomatic brain hemorrhage showed a significantly increased inflammatory enzyme upregulation from both COX-2 (p < 0.001) and NLRP3 (p = 0.009) versus patients with symptomatic CCM-related epilepsy at first diagnosis. Conclusions: Inflammatory processes in CCMs seem to be driven by broad and multiple pathways because both COX-2 and NLRP3-driven inflammatory pathways are consistently activated. As a novelty, this study showed that patients with symptomatic hemorrhage showed upregulated inflammatory enzyme activity compared to patients with CCM-related epilepsy. No direct links between NLRP3, COX-2 expression, and radiological, pathological, or preexisting patient conditions were found. Full article

Objective: Oral frailty is associated with an increased risk of cognitive decline, yet practical tools for early identification remain limited. The Oral Frailty 5-item Checklist (OF-5), recently standardized in Japan, does not account for severe tooth loss, which is a known risk factor for brain atrophy. We developed a revised version of the OF-5 that includes the criterion of having nine or fewer teeth. This study aimed to validate the revised OF-5 as a screening tool for detecting early brain structural changes related to dementia risk in cognitively unimpaired older adults. Methods: We analyzed 732 cognitively unimpaired participants from a population-based Japanese cohort (baseline 2016–2018). Oral frailty was assessed using both the original OF-5 and the revised OF-5. Brain volumes were measured by MRI and processed with FreeSurfer. Associations between oral frailty status and regional brain volumes were tested using multivariable-adjusted models, with further adjustment for nutrient intake and food consumption. Results: The revised OF-5, which adds severe tooth loss (≥9 teeth) as a criterion, showed greater sensitivity in detecting dementia-related brain changes than the original version. With the original OF-5, oral frailty was associated only with reduced fusiform gyrus volume (1.088% vs. 1.109% of estimated total intracranial volume [eTIV]; p < 0.05). In contrast, the revised OF-5 detected broader changes: orally frail participants showed significantly higher white matter hyperintensity (WMH) volume (0.366% vs. 0.302% of eTIV; p < 0.05) and smaller volumes in the medial temporal lobe (1.824% vs. 1.856%), pars triangularis (0.401% vs. 0.412%), and fusiform gyrus (1.080% vs. 1.111%)—all p < 0.05 (FWE-corrected). These associations persisted after adjusting for nutrient intake and food consumption. Conclusions: The revised OF-5 improves identification of pre-symptomatic brain changes in cognitively healthy older adults, independent of nutrition. It may serve as a simple and practical tool for early screening of dementia risk in clinical and community settings. Full article

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. It is characterized by a high degree of heterogeneity, meaning that although these tumors may appear morphologically similar, they often exhibit distinct clinical outcomes. By associating specific molecular fingerprints with different clinical behaviors, high-throughput omics technologies (e.g., genomics, transcriptomics, and epigenomics) have significantly advanced our understanding of GBM, particularly of its extensive heterogeneity, by proposing a molecular classification for the implementation of precision medicine. However, due to the vast volume and complexity of data, the integrative analysis of omics data demands substantial computational power for processing, analyzing and interpreting GBM-related data. Artificial intelligence (AI), which mainly includes machine learning (ML) and deep learning (DL) computational approaches, now presents a unique opportunity to infer valuable biological insights from omics data and enhance the clinical management of GBM. In this review, we explored the potential of integrating multi-omics, imaging radiomics and clinical data with AI to uncover different aspects of GBM (molecular profiling, prognosis, and treatment) and improve its clinical management. Full article

Background/Objectives: Studies have shown that higher polygenic risk scores (PRSs) for Alzheimer’s disease (AD) are associated with smaller volumes in temporal brain regions typically affected by this disease. These effects have also been found in cognitively unimpaired (CU) older adults. This study aimed to investigate the relationship between PRSs and brain volumes in specific areas associated with early AD. Methods: 342 participants were selected from the Alzheimer’s Disease Neuroimaging Initiative and stratified into three groups: 114 amyloid-positive atrophic (A+N+), 114 amyloid-negative non-atrophic (A−N−), and 114 amyloid-positive non-atrophic (A+N−) people. Linear regressions were performed within each group to investigate associations between PRSs and regional grey matter volumes. Analyses were also repeated after stratifying groups by APOE status and clinical diagnosis. Two sensitivity analyses were run to investigate the impact of APOE and amyloid status and concordance across biomarkers. Multiplicity was controlled for using the Benjamini–Hochberg false discovery rate (FDR) approach. Results: Negative associations were observed between PRSs and volumes of the left amygdala and hippocampus in A+N+, right hippocampus in A+N−, and right posterior cingulate cortex in A−N− participants. Associations were found especially in A−N− participants, both ε4 allele carriers and non-carriers, and mostly confirmed in sensitivity analyses. Associations emerged only in CU and AD participants, but not in people with MCI. None of these findings survived correction for FDR. Conclusions: These findings highlight the potential of PRSs as novel biological indicators for a deeper characterisation of AD-related neural alterations. Full article

A 9.4T brain MRI is the highest resolution MRI scanner in the public market. It offers submillimeter brain imaging with exceptional anatomical detail, making it one of the most powerful tools for detecting subtle structural changes associated with neurological conditions. Current segmentation models are optimized for lower-field MRI (1.5T–3T), and they struggle to perform well on 9.4T data. In this study, we present the GA-MS-UNet++, the world’s first deep learning-based model specifically designed for 9.4T brain MRI segmentation. Our model integrates multi-scale residual blocks, gated skip connections, and spatial channel attention mechanisms to improve both local and global feature extraction. The model was trained and evaluated on 12 patients in the UltraCortex 9.4T dataset and benchmarked against four leading segmentation models (Attention U-Net, Nested U-Net, VDSR, and R2UNet). The GA-MS-UNet++ achieved a state-of-the-art performance across both evaluation sets. When tested against manual, radiologist-reviewed ground truth masks, the model achieved a Dice score of 0.93. On a separate test set using SynthSeg-generated masks as the ground truth, the Dice score was 0.89. Across both evaluations, the model achieved an overall accuracy of 97.29%, precision of 90.02%, and recall of 94.00%. Statistical validation using the Wilcoxon signed-rank test (p < 1 × 10⁻⁵) and Kruskal–Wallis test (H = 26,281.98, p < 1 × 10⁻⁵) confirmed the significance of these results. Qualitative comparisons also showed a near-exact alignment with ground truth masks, particularly in areas such as the ventricles and gray–white matter interfaces. Volumetric validation further demonstrated a high correlation (R² = 0.90) between the predicted and ground truth brain volumes. Despite the limited annotated data, the GA-MS-UNet++ maintained a strong performance and has the potential for clinical use. This algorithm represents the first publicly available segmentation model for 9.4T imaging, providing a powerful tool for high-resolution brain segmentation and driving progress in automated neuroimaging analysis. Full article

Background: Glioblastoma (GBM), IDH-wildtype, is one of the most aggressive primary brain malignancies, and maximal safe resection is consistently recognized as a significant prognostic factor. Intraoperative adjuncts including functional mapping, neuronavigation, and fluorescence-guidance are not always present in many centers around the world. The aim is not to suggest equivalence to adjunct-assisted resections, but rather to illustrate the feasibility of anatomy-guided surgery in carefully selected cases and to contribute to the broader discussion on safe operative strategies in resource-limited environments. Methods: We present the case of a 54-year-old right-handed male who presented with progressive non-fluent aphasia, seizures, and signs of intracranial hypertension. Pre-operative MRI showed a heterogeneously hyperintense, frontobasal intra-axial mass involving the dominant inferior frontal gyrus, extending toward the corpus callosum and orbitofrontal cortex, and early subfalcine shift. Surgery was performed via a left frontobasal craniotomy, using subpial dissection and cortical–sulcal anatomical landmarks while aiming to preserve eloquent subcortical tracts (frontal aslant tract, superior longitudinal fasciculus). Nueronavigation, functional mapping or fluorescence was not used. We defined our outcomes by the extent of resection, functional preservation, and early radiological stability. Results: The procedure achieved a subtotal-near-total resection (>95% estimated volume) while maintaining functional motor function from prior to surgery and the patient’s baseline expressive aphasia, with no new neurological deficits. Early post-operative CT showed decompression of the resection cavity without hemorrhage or shift. At three months post-operative, CT showed stability of the cavity and resolution of the most perilesional edema with no evidence of recurrence. Clinically, the patient showed gradual improvement in verbal fluency, he remained seizure free, and maintained independence, which allowed for timeliness of the initiation of adjuvant chemoradiotherapy. Conclusions: We intend for the case to illustrate that, in selected dominant frontal GBM, following microsurgical anatomical principles closely may provide a high extent of resection with the preservation of function, even without advanced intraoperative adjuncts. We hope that our experience may support our colleagues who practice in resource-limited settings and contribute to our shared goal of both oncological outcomes and the quality of life of our patients. Full article

Background/Objectives: Maternal vitamin supplementation (including folic acid, vitamin D, and multivitamin supplements) during pregnancy may lower the likelihood of neurodevelopmental disorders in offspring. This study examines the associations between maternal vitamin suppletion during pregnancy and morphological patterns in offsprings’ brain structure and traits of Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) in a large population-based study of child development. Methods: The study cohort included a total of 3937 children (aged 9–11) participating in the Generation R cohort in Rotterdam, the Netherlands. Maternal vitamin D and folateserum levels, multivitamin supplement use, and overall dietary quality (as assessed by the Food Frequency Questionnaire, FFQ) during pregnancy were used as predictors. T1 structural MRI scans were acquired and segmented using Freesurfer to assess brain morphometry. Cortical and subcortical brain volumes of children were separated into four independent components and used as mediators. ADHD and ASD traits, as measured by parent-completed questionnaires (Child Behavior CheckList and Social Responsiveness Scale, respectively) were used as outcome variables. Results: Results show that (1) maternal vitamin D, multivitamin supplementation, and better diet quality were associated with fewer ADHD or ASD traits in the offspring; (2) vitamin D and diet quality were associated with larger-volume childhood brain components; (3) larger-volume brain components were associated with fewer ADHD and ASD traits; (4) part of the association between dietary factors in pregnancy and offspring ADHD and ASD traits was mediated through the brain volumes of the children. Conclusions: Though all observed effect sizes were small, further population-based research should be performed to further delineate the effects of gestational multivitamin and vitamin D exposure and investigate whether this may be an avenue for preventive interventions. Full article

The increasing prevalence of brain metastases in cancer patients due to longer life expectancy and improvements in neuroimaging highlights the need for effective local treatments. Despite advancements in systemic targeted therapies, their low blood–brain barrier (BBB) penetrance limits their intracranial efficacy. Stereotactic radiosurgery (SRS) has largely supplanted whole-brain radiation therapy (WBRT) for patients with up to 10 brain lesions due to superior neurocognitive outcomes and high local control. While single-fraction SRS provides low radiation toxicity with smaller lesions, high-volume metastases necessitate doses above tolerance limits to achieve comparable local control. As tumor volume increases, the number of tumor cells also increases, requiring higher doses of radiation than the maximum tolerated doses reported in the RTOG 9005 study to achieve tumor control. Hypo-fractionated SRS (HySRS) permits the delivery of high radiation doses over 2–5 fractions, thus mitigating the risk of radiation toxicity while maintaining high local control. This review presents the available evidence and ongoing clinical trials on HySRS for the management of brain metastases. Full article

Background/Objectives: This study examined the efficacy of essential amino acid (EAA) supplementation on changes in behavior and hippocampal neurotrophin, dopaminergic and serotonergic markers to a volume overload stress resembling an overtraining syndrome. Methods: Thirty-two 3-month-old male C57Bl/6J mice were randomized into four groups: Resistance training (RT), resistance training with overtraining (RTO), resistance training with overtraining and EAA (RTOEAA), or control. Mice in RTOEAA received EAA supplementation (1.5 g·kg·day⁻¹), while the other groups received a sham treatment. A 5-week resistance training protocol was employed. Training volume was increased two-fold during the final two weeks for RTO and RTOEAA to cause the OTS. EAA intervention for RTOEAA occurred during the OTS. Results: A significant decline in the maximum resistance carrying load in RTO compared to RT (p = 0.002) and RTOEAA (p = 0.029) confirmed that the animals in that group were overtrained. Significantly greater average latency times for RTO compared to RT (p = 0.009) and C (p = 0.05) indicated that the OTS caused spatial memory deficits in animals that were not supplemented. These latter changes may have been related to the significant declines in brain derived neurotrophic (BDNF) expression and elevations in dopamine 1 receptor (D1R) expressions. Increased resiliency for RTOEAA may have been related to the effect of EAA on stimulating significant increases in the expression of hippocampal tyrosine receptor kinase B (TrkB) and serotonin receptors (5-HT1A). Conclusions: EAA supplementation during a resistance model of overtraining appeared to provide increased resiliency to OTS by maintaining neurotrophin expression and enhancing serotonergic adaptation. Full article

Purpose: To analyze the structural changes in the brain related to combined hearing and vision loss in patients with Usher syndrome (USH) obtained by 7 Tesla MRI. Methods: Twenty patients with a diagnosis of USH and fifteen normal age- and gender-matched subjects were included in this study. USH patients underwent ophthalmological examination. All subjects underwent 7 Tesla MRI of the brain in two sequences: 3D BRAVO T1-weighted and 3D MT-weighted SILENT sequence. Results: Mean values of LGN volumes (right 95.65 mm³, left 88.61 mm³) are significantly (p < 0.001) lower in the USH group than in the control group (right 126.64 mm³, left 120.37 mm³). The average volumes of the left cuneus (4102.85 mm³), right parsorbitalis (2133.95 mm³), and right rostralanteriorcingulate cortex (ACC) (1727.60 mm³) in the patient group are significantly (p = 0.03673, 0.02434, and 0.04204, respectively) lower than in the control group (4673.73 mm³, 2485.13 mm³, and 2060.00 mm³, respectively). Mean lengths of the left lingual cortex (1.99 mm) and right pericalcarine cortex (1.84 mm) in the patient group are significantly (p = 0.02449 and 0.03153, respectively) smaller than in the control group (2.09 mm and 2.0 mm, respectively). Average lengths of the right insula (2.74 mm) in the patient group are significantly (p = 0.00041) greater than in the control group (2.49 mm). Conclusions: Parts of the brain engaged in the visual processing as LGN, pericalcarine cortex, lingual gyrus, and cuneus, are decreased, as well as those involved in hearing and language processing, such as parsorbitalis and ACC. The insula, a higher-order brain area possessing a crucial role in olfactory processing, is increased in USH patients. Our findings enhance the understanding of structural brain abnormalities related to combined hearing and vision loss and suggest complex adaptive changes that should be considered in the development of new visual rehabilitation and restitution strategies in USH patients. Full article

Gyrification, the folding of the cerebral cortex, plays a crucial role in brain development and function. Perinatal hypoxia–ischemia (HI) is a leading cause of neonatal brain injury, affecting cortical folding that can be measured by the gyrification index (GI). Using a late-preterm ferret model, our objective was to explore the relationships between HI injury, GI changes, and behavior, as well as the potential moderating effects of sex and treatment. Animals received 3 mg/kg E. coli lipopolysaccharide and underwent bilateral carotid artery ligation followed by alternating hypoxia and hyperoxia (HIH) and were randomized to saline vehicle (n = 25), erythropoietin (n = 20), therapeutic hypothermia (6 h at 33.5 °C, n = 20), and uridine monophosphate (n = 6), with n = 20 unexposed littermates serving as controls. Early reflex testing, CatWalk gait analysis, open-field behavior, and an open-water swim test were performed. Average, peak, motor, and somatosensory strip GIs were then assessed using ex vivo MRI. In control animals, males had lower GI than females; however, HIH exposure resulted in male GI being more similar to females, where HIH animals had significantly higher average GI than controls (p = 0.02). Adjusting for brain volume and injury, GIs in motor and somatosensory areas were associated with faster reflex outcomes in males but not females. In female controls, motor and somatosensory GIs were associated with increased anxiety-like behaviors, such as spending less time in open water during the swim test. By comparison, in male controls, higher GI was associated with decreased anxiety-like behaviors, including higher exploration index in the swim test. These sex-specific relationships between GI and behavior were lost with HIH injury. Treatment did not meaningfully restore the relationship between GI and behavior after HIH, but targeting this outcome may be an important measure for use in future neuroprotection studies in the ferret. Full article

Purpose: Focal cortical dysplasia (FCD) is a common developmental malformation disease of the cerebral cortex. Although mounting evidence has suggested that FCD lesions have variable locations and topographies throughout the cortex, few studies have explored consistencies in structural connectivity among different lesion types. In this study, we analyzed microscopic structural changes via lesion analysis and explored structural changes in nonlesion regions across the brain. Methods: Diffusion tensor imaging (DTI) and magnetization transfer imaging were used to compare FCD lesions and contralateral normal appearing gray/white matter (cNAG/WM). Voxel-based morphometry was calculated for 28 children with FCD and 34 sex- and age-matched healthy participants. DTI indices of the FCD and healthy control groups were analyzed via the tract-based spatial statistic method to evaluate the microstructure abnormalities of WM fiber tracts in individuals with FCD. Results: In terms of FCD lesions, compared with those of the cNAG, the fractional anisotropy (FA) values were decreased, and the mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased; the magnetization transfer ratios were also decreased. In terms of whole-brain changes due to FCD, compared with the healthy control group, the FCD group showed a decrease in the volume of the right hippocampus and left anterior cingulate cortex. FCD patients had lower FA values, higher MD values, lower AD values, and mainly increased RD values in relation to WM microstructure. Conclusions: Microstructural abnormalities outside lesion regions may be related to injury to the epileptic network, and the identification of such abnormalities may complement diagnoses of FCD in pediatric patients. Full article

Recently, there has been rising interest in the use of cannabis and its derivatives as therapeutic tools to support brain health, particularly in athletes. Cannabis-based substances interact with the endogenous cannabinoid (i.e., endocannabinoid) system, which is involved in widespread physiological processes that contribute to brain function. In other work, the benefits of exercise for brain health have been prominently noted. Despite large bodies of work on both cannabinoid and exercise influences on brain function, there is an understudied overlap in their physiological effects that may be especially important in athletic populations regularly engaged in high volumes of exercise. This narrative review describes mechanistic overlaps between cannabinoid and exercise effects on brain function. The literature search was broad, emphasizing research published since 2010 and including randomized clinical trials, observational studies, case studies, preclinical work, both human and animal studies, and information presented in related review articles. The focal point of the current review is the potentially overlapping effects of cannabinoids and exercise on brain function via physiological processes underpinning inflammation, vascular function, and neuroplasticity. Mechanisms are described in detail with consideration of common and contrasting influences of cannabinoids and exercise on the brain. Altogether, the compiled information suggests that indirect and direct interactions between these two therapeutic avenues have potential to introduce additive, synergistic, or opposing effects. Considering such interactions will be critical in optimizing therapeutic strategies involving cannabinoids as they are increasingly applied in the sport sciences and beyond. Full article