Search Results (205)

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

Radiation therapy serves as a fundamental treatment for primary and metastatic brain tumors, whether used alone or combined with surgery and chemotherapy. Despite its oncological efficacy, this treatment paradigm frequently induces radiation-induced brain injury (RBI), a progressive neuropathological condition characterized by structural and functional damage to healthy cerebral parenchyma. Patients with RBI frequently develop affective disorders, particularly major depressive disorder and generalized anxiety disorder, which profoundly impair psychosocial functioning and quality of life. The pathophysiology involves complex mechanisms such as neuroinflammation, oxidative stress, blood–brain barrier disruption, and white matter damage. Current management strategies include antidepressants, corticosteroids, and neuroprotective agents, while emerging therapies targeting neuroinflammation and neural repair show promise. This review comprehensively examines the pathogenesis of RBI-related affective disorders and evaluates both conventional and novel treatment approaches. By synthesizing current evidence, we aim to provide insights for developing more effective interventions to improve patient outcomes and quality of life. Full article

Objectives: Methamphetamine (MA) abuse during adolescence can have a significant impact on brain development. On the other hand, regular exercise is known to promote brain health and may have neuroprotective effects. The purpose of this study is to compare brain volumes in three different adolescent groups: those with active methamphetamine use disorder (MUD), adolescent athletes who regularly exercise, and healthy control adolescents. Methods: This MRI study involved three groups of adolescents: 10 with active MUD (9 males, 1 female), nine licensed runner adolescents (three males, six females), and 10 healthy adolescents (5 males, 5 females). Brain volumes were analyzed using T1-weighted images from a 3.0 Tesla MRI scanner, and then segmented automatically with vol2Brain. Statistical analyses included ANCOVA with sex as a covariate and LSD post hoc tests performed using SPSS Statistics 23. Results: Adolescents with MUD showed a 10% increase in total white matter volume compared to the athlete group. Conversely, cortical gray matter volume was reduced by 4% compared to the healthy control group and by 7% compared to the athlete group. The frontal and insular cortices in the MUD group had significantly diminished volumes compared to the athlete group. Overall, individuals with MUD had decreased gray matter volumes and increased white matter volumes in their brains. The brain volumetric differences between the MUD group and the athlete group were statistically significant. Conclusions: The brains of those with MUD displayed a reduction in gray matter volume and an increase in white matter volume, indicating damage from MA on the developing adolescent brain. The volumetric disparities between the MUD and athlete groups were found to be significantly different, suggesting a possible neuroprotective factor of exercise. Further studies are required to explore the potential of exercise-based interventions in alleviating the harmful effects of MA abuse. Full article

Background: The ability of Graph Neural Networks (GNNs) to analyse brain structural patterns in various kinds of neurodegenerative diseases, including Parkinson’s disease (PD), has drawn a lot of interest recently. One emerging technique in this field is brain age prediction, which estimates biological age to identify ageing patterns that may serve as biomarkers for such disorders. However, a significant problem with most of the GNNs is their depth, which can lead to issues like oversmoothing and diminishing gradients. Methods: In this study, we propose SAGEFusionNet, a GNN architecture specifically designed to enhance brain age prediction and assess PD-related brain ageing patterns using T1-weighted structural MRI (sMRI). SAGEFusionNet learns important ROIs for brain age prediction by incorporating ROI-aware pooling at every layer to overcome the above challenges. Additionally, it incorporates multi-layer feature fusion to capture multi-scale structural information across the network hierarchy and auxiliary supervision to enhance gradient flow and feature learning at multiple depths. The dataset utilised in this study was sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. It included a total of 580 T1-weighted sMRI scans from healthy individuals. The brain sMRI scans were parcellated into 56 regions of interest (ROIs) using the LPBA40 brain atlas in CAT12. The anatomical graph was constructed based on grey matter (GM) volume features. This graph served as input to the GNN models, along with GM and white matter (WM) volume as node features. All models were trained using 5-fold cross-validation to predict brain age and subsequently tested for performance evaluation. Results: The proposed framework achieved a mean absolute error (MAE) of $4.24\pm 0.38$ years and a mean Pearson’s Correlation Coefficient (PCC) of $0.72\pm 0.03$ during cross-validation. We also used 215 PD patient scans from the Parkinson’s Progression Markers Initiative (PPMI) database to assess the model’s performance and validate it. The initial findings revealed that out of 215 individuals with Parkinson’s disease, 213 showed higher and 2 showed lower predicted brain ages than their actual ages, with a mean MAE of 13.36 years (95% confidence interval: 12.51–14.28). Conclusions: These results suggest that brain age prediction using the proposed method may provide important insights into neurodegenerative diseases. Full article

Early-life brain injuries are major causes of long-term neurodevelopmental disorders such as cerebral palsy. Emerging evidence suggests these injuries can alter the gut microbiota composition, intestinal integrity, and neuroinflammatory responses. This systematic review evaluated the impact of early-life brain injuries on the gut microbiota in rodent models. A scientific literature search was conducted across Medline/PubMed, Web of Science, Scopus, and Embase. Initially, 7419 records were identified, and 21 eligible studies were included. Eligible studies focused on evaluating the microbiota alterations and related gut–brain axis markers at the neonatal or post-weaning stages. The data extraction and synthesis followed PRISMA guidelines. Most studies reported gut dysbiosis characterized by a decreased abundance of Bacteroidetes, and Lactobacillus. Alterations were associated with an increased gut permeability, reduced tight junction proteins, and elevated pro-inflammatory cytokines. Several studies showed reduced levels of short-chain fatty acids and metabolic pathway disruptions. Brain outcomes included neuroinflammation, white matter injury, altered gene expression, and impaired structural integrity. These results suggest that early-life brain injury induces complex alterations in the gut microbiota and its metabolic products, which may contribute to systemic and neuroinflammatory processes. Understanding these interactions offers insights into the pathophysiology of neurodevelopmental disorders and highlights the gut–brain axis as a potential target for early interventions. Full article

Background/Objectives: This study aims to investigate the influence of demographic, behavioral, anthropometric, and comorbid factors on brain atrophy in people living with HIV (PLWH). Methods: We conducted a cross-sectional study involving 121 HIV-positive patients, stratified into two groups, those with and without brain atrophy (BA). For each participant, we recorded demographic data, smoking status, physical activity levels, disease and treatment duration, and comorbidities. BA was quantitatively assessed using MRI-derived volumetric measurements of 47 cerebral substructures. Results: Patients with BA exhibited significantly reduced gray matter (GM) and white matter (WM) volumes alongside increased cerebrospinal fluid volumes, both in absolute and percentage measurements. WM atrophy was most pronounced in the frontal, parietal, and temporal lobes, with relative sparing of the occipital lobe. GM atrophy predominantly affected the basal ganglia (notably, the thalamus and putamen) and cortical regions, including the hippocampus, frontal, and parietal lobes. Significant positive correlations were observed between BA and both smoking status (pack–years) and disease duration, while physical activity demonstrated an inverse relationship (higher atrophy risk in those with less than 30 min of daily continuous walking). Non-adherence to antiretroviral therapy (ART) was also associated with BA. Among comorbidities, type 2 diabetes and HIV-associated neurocognitive disorders (HAND) showed the strongest associations with BA. Conclusions: Brain atrophy in PWH is correlated with smoking, physical inactivity, and the duration of HIV infection. Comorbid conditions, such as type II diabetes and HAND, amplify the risk for BA. We consider that early lifestyle interventions and optimized ART may mitigate the neurodegeneration process. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

Background: Toxic oil syndrome (TOS) was a major food-borne epidemic that occurred in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While the somatic sequelae of TOS have been well documented, its long-term cognitive consequences remain poorly understood more than four decades after exposure. Methods: In this case-control study, 50 individuals with clinically confirmed TOS were compared to 50 healthy controls matched for age, sex, and education. All participants completed a comprehensive neuropsychological assessment, along with questionnaires evaluating fatigue, anxiety, depression, and health-related quality of life. Multivariate regression models were adjusted for demographic and vascular risk factors, as well as for mood symptoms, fatigue, and use of central nervous system-acting medications. Structural equation modeling was used to explore the potential mediating effects of affective and fatigue symptoms on cognitive performance. Results: TOS survivors showed significantly poorer performance than controls in attention, executive function, processing speed, and global cognition after adjusting for demographic and vascular risk factors. However, these differences were no longer statistically significant after additional adjustment for fatigue, depression, anxiety, and central nervous system-acting medications. Structural equation modeling analyses revealed that affective symptoms—particularly fatigue—substantially mediated the relationship between TOS and cognitive performance. Conclusions: The cognitive profile observed mirrors that of disorders characterized by subcortical dysfunction and impaired neural connectivity, such as multiple sclerosis and vascular cognitive impairment. Although early postmortem studies in TOS did not demonstrate overt white matter lesions, our findings raise the possibility of long-lasting alterations involving both white and gray matter networks. These results emphasize the need to consider mood and fatigue symptoms when evaluating cognition in TOS survivors and point to the potential for widespread, enduring neurobiological effects stemming from the original toxic exposure. Full article

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cognitive decline, gait disturbances, and urinary incontinence. Surgical interventions such as ventriculoperitoneal shunt (VPS) and endoscopic third ventriculostomy (ETV) are the primary treatment options. While VPS is the standard of care, ETV offers a minimally invasive alternative with potentially fewer complications. However, comparative evidence regarding their impact on cognitive, motor, and structural outcomes remains limited. This study, titled ENVENTOR-iNPH (endoscopic ventriculostomy versus shunt on neuropsychological and motor performance in patients with iNPH), aims to address this gap through a rigorously designed comparative protocol. Methods: This protocol is designed as a multicenter, randomized, controlled trial (ENVENTOR-iNPH) to compare the effects of ETV and VPS in patients diagnosed with iNPH. The study will enroll 100 patients aged 60 years or older, randomly assigned to undergo ETV (n = 50) or VPS (n = 50). Preoperative and postoperative evaluations will include comprehensive cognitive and motor assessments, standardized quality-of-life instruments, and advanced neuroimaging techniques such as MRI with flowmetry and diffusion tensor imaging (DTI). Functional outcomes will also be evaluated using navigated transcranial magnetic stimulation (nTMS) and wearable motion analysis systems. The objective of this study is to compare the efficacy and safety of ETV versus VPS in restoring cognitive and motor performance in patients with iNPH. Results: Primary outcomes include cognitive and motor function improvements. Secondary endpoints are surgical complications, hospital stay duration, and changes in quality of life. Neuroimaging will assess changes in white matter integrity and cerebrospinal fluid dynamics, while nTMS will provide insights into neuroplasticity and motor pathway recovery. ETV is hypothesized to demonstrate clinical outcomes comparable or superior to VPS, particularly in terms of complication reduction and hospital recovery metrics. Conclusions: The ENVENTOR-iNPH protocol establishes the framework for a comprehensive, multicenter study comparing ETV and VPS in iNPH patients. The findings from this initial study will inform the design of larger-scale multicenter trials, guide clinical decision making, and potentially position ETV as a preferred treatment option for eligible patients. Full article

Hypothermia (HT) is used clinically for neonatal hypoxic–ischemic encephalopathy (HIE); however, the brain protection is incomplete and selective regional vulnerability and lifelong consequences remain. Refractory damage and impairment with HT cooling/rewarming could result from unchecked or altered persisting cell death and proteinopathy. We tested two hypotheses: (1) HT modifies neurodegeneration type, and (2) intrinsically disordered proteins (IDPs) and encephalopathy cause toxic conformer protein (TCP) proteinopathy neonatally. We studied postmortem human neonatal HIE cases with or without therapeutic HT, neonatal piglets subjected to global hypoxia-ischemia (HI) with and without HT or combinations of HI and quinolinic acid (QA) excitotoxicity surviving for 29–96 h to 14 days, and human oligodendrocytes and neurons exposed to QA for cell models. In human and piglet encephalopathies with normothermia, the neuropathology by hematoxylin and eosin staining was similar; necrotic cell degeneration predominated. With HT, neurodegeneration morphology shifted to apoptosis-necrosis hybrid and apoptotic forms in human HIE, while neurons in HI piglets were unshifting and protected robustly. Oligomers and putative TCPs of α-synuclein (αSyn), nitrated-Syn and aggregated αSyn, misfolded/oxidized superoxide dismutase-1 (SOD1), and prion protein (PrP) were detected with highly specific antibodies by immunohistochemistry, immunofluorescence, and immunoblotting. αSyn and SOD1 TCPs were seen in human HIE brains regardless of HT treatment. αSyn and SOD1 TCPs were detected as early as 29 h after injury in piglets and QA-injured human oligodendrocytes and neurons in culture. Cell immunophenotyping by immunofluorescence showed αSyn detected with antibodies to aggregated/oligomerized protein; nitrated-Syn accumulated in neurons, sometimes appearing as focal dendritic aggregations. Co-localization also showed aberrant αSyn accumulating in presynaptic terminals. Proteinase K-resistant PrP accumulated in ischemic Purkinje cells, and their target regions had PrP-positive neuritic plaque-like pathology. Immunofluorescence revealed misfolded/oxidized SOD1 in neurons, axons, astrocytes, and oligodendrocytes. HT attenuated TCP formation in piglets. We conclude that HT differentially affects brain damage in humans and piglets. HT shifts neuronal cell death to other forms in human while blocking ischemic necrosis in piglet for sustained protection. HI and excitotoxicity also acutely induce formation of TCPs and prion-like proteins from IDPs globally throughout the brain in gray matter and white matter. HT attenuates proteinopathy in piglets but seemingly not in humans. Shifting of cell death type and aberrant toxic protein formation could explain the selective system vulnerability, connectome spreading, and persistent damage seen in neonatal HIE leading to lifelong consequences even after HT treatment. Full article

Background: Volumetric analysis and segmentation of magnetic resonance imaging (MRI) data is an important tool for evaluating neurological disease progression and neurodevelopment. Fully automated segmentation pipelines offer faster and more reproducible results. However, since these analysis pipelines were trained on or run based on atlases consisting of neurotypical controls, it is important to evaluate how accurate these methods are for neurodegenerative diseases. In this study, we compared five fully automated segmentation pipelines, including FSL, Freesurfer, volBrain, SPM12, and SimNIBS, with a manual segmentation process in GM1 gangliosidosis patients and neurotypical controls. Methods: We analyzed 45 MRI scans from 16 juvenile GM1 gangliosidosis patients, 11 MRI scans from 8 late-infantile GM1 gangliosidosis patients, and 19 MRI scans from 11 neurotypical controls. We compared the results for seven brain structures, including volumes of the total brain, bilateral thalamus, ventricles, bilateral caudate nucleus, bilateral lentiform nucleus, corpus callosum, and cerebellum. Results: We found volBrain’s vol2Brain pipeline to have the strongest correlations with the manual segmentation process for the whole brain, ventricles, and thalamus. We also found Freesurfer’s recon-all pipeline to have the strongest correlations with the manual segmentation process for the caudate nucleus. For the cerebellum, we found a combination of volBrain’s vol2Brain and SimNIBS’ headreco to have the strongest correlations, depending on the cohort. For the lentiform nucleus, we found a combination of recon-all and FSL’s FIRST to give the strongest correlations, depending on the cohort. Lastly, we found segmentation of the corpus callosum to be highly variable. Conclusions: Previous studies have considered automated segmentation techniques to be unreliable, particularly in neurodegenerative diseases. However, in our study, we produced results comparable to those obtained with a manual segmentation process. While manual segmentation processes conducted by neuroradiologists remain the gold standard, we present evidence to the capabilities and advantages of using an automated process that includes the ability to segment white matter throughout the brain or analyze large datasets, which pose feasibility issues to fully manual processes. Future investigations should consider the use of artificial intelligence-based segmentation pipelines to determine their accuracy in GM1 gangliosidosis, lysosomal storage disorders, and other neurodegenerative diseases. Full article

Background/Objectives: Cerebral folate transporter deficiency is characterized by pauses and regression in general development stages, with ataxia, choreoathetoid movements, and myoclonic epilepsy generally resistant to treatment. The aim of this study was to comprehensively evaluate cases followed up in two centres in Türkiye for a diagnosis of folate receptor-α deficiency. Methods: The study included nine cases from six different families. Results: The patients comprised 22.2% males and there was parental consanguinity in 88.9% of cases. The mean age at which complaints were first noticed was 3.7 years, and the age of definitive diagnosis was 10.4 years. The most frequently seen first complaints were febrile convulsions and attention deficit-hyperactivity-learning difficulties. The diagnosis most commonly made before the definitive diagnosis was epilepsy, and the first seizure occurred at a mean of 5.2 years. On cranial imaging, white matter involvement, cerebellar atrophy and cerebral atrophy were determined most often. Definitive diagnosis was established solely through clinical findings and genetic analysis. Three different variants in the FOLR1 gene were determined. Treatment with folinic acid at a dose of 5.2 mg/kg/day of PO was started at the age of 9.8 years on average, and intravenous folinate was started at different doses. Conclusions: This study stands out as one of the largest case series in the literature and identifies a previously unreported novel variant. Our study suggests that FOLR1-related CFD should be considered in cases with febrile convulsions, developmental delay, ataxia, autism spectrum disorder, acquired microcephaly, and MRI findings of white matter involvement and cerebellar atrophy. Due to an asymptomatic early period, CFD diagnosis may be delayed, and treatment after symptom onset may be less effective. Incorporating FOLR1 gene analysis into newborn screening programmes could facilitate early diagnosis and treatment. It is thought that the application of vagus nerve stimulation, in addition to folinic acid and anticonvulsant drug treatment, could be effective in seizure control. Full article

Background: Inherited white matter (WM) disorders of the central nervous systems (CNS), or leukodystrophies, are devastating diseases that primarily affect children, many of whom die early in life or suffer from long-term disability. Methods: q-Space diffusion MR imaging (QSI) and diffusion tensor MR imaging (DTI) with the same resolution and timing parameters were used to study the spinal cords (SCs) of two myelin mutants that are experimental models of WM diseases of different severity, namely the 28-day-old taiep and Long–Evans Shaker (les) rats. The aim was to verify if and which of the diffusion methodologies used is more suitable for early detection of the milder taiep pathology and to characterize its early phase. We also aimed to compare the diffusion MRI results with quantitative electron microscopy (EM) findings. Results: We found that at this early age (28 days), both QSI and DTI were able to detect the severe les WM pathology, while the milder WM pathology in the SC of the taiep rats was detected only by QSI. An increase in the mean radial displacement (RaDis), representing the MRI axon diameter (AD), and a decrease in the probability for zero displacement (PZD) were observed in the dorsal column (ROI 1) of the taiep SCs. In other WM areas, the same trends were observed but the differences were not of statistical significance. In DTI, we found some lower fractional anisotropy (FA) values in the taiep SCs compared to the controls; however, these differences were not statistically significant. For the more severe les pathology, we observed a dramatic increase in the RaDis values and a large decrease in PZD values in all ROIs examined. There, even the FA values were lower than that of the control SCs in all ROIs, albeit with much smaller statistical significance. These MRI results, which show a higher detectability of WM pathology with heavier diffusion weighting, followed histological findings that showed significant myelin deficiency in the dorsal column in the taiep SCs and a practically complete myelin loss in all WM areas in the les SCs. This study also revealed that, under the experimental conditions used here, the apparent increase in RaDis agrees better with myelin thickness and not with average AD extracted form EM, probably reflecting the effect of water exchange. Conclusions: These results, corroborated by diffusion time-dependent QSI, also imply that while diffusion MRI in general and QSI in particular provide acceptable apparent axon diameter estimations in heathy and mature WM, this appears not to be the case in severely damaged WM where exchange appears to play a more important role. Full article

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder. Neuropsychiatric manifestations are frequently observed and are associated with increased morbidity and reduced quality of life. Magnetic resonance imaging (MRI) is the neuroimaging procedure of choice for investigation. High-resolution vessel wall imaging (HRVWI) is a neuroimaging methodology that allows active mapping of pathophysiological processes involving brain vessel walls. Methods: To exemplify the importance of HRVWI and its usefulness in patients with SLE, we carried out a scoping review (following PRISMA guidelines) using the PubMed and Embase databases. Results: We retrieved 10 studies that utilized HRVWI in neuropsychiatric SLE, including a total of 69 patients. The majority, 84% (58/69), were women, with ages ranging between 16 and 80 years (average 38.4 years). Approximately 46.3% (32/69) of patients had white matter lesions in the brain at the time of investigation, and 77% (53/69) had normal magnetic resonance angiography. Treatment with immunosuppressants led to the resolution of the majority of the findings. Conclusions: Imaging plays an important role in investigating neuropsychiatric SLE. HRVWI analysis is gaining more importance, with its ability to identify inflammation even if angiographic MRI sequences (3D TOF) are normal, allowing the institution of early immunosuppressant treatment and resolution of symptoms. Full article