Search Results (162)

Among brain regions, the cerebellum (CBL) has traditionally been associated with motor control. However, increasing evidence from connectomics and functional imaging has expanded this view, revealing its involvement in a wide range of cognitive and integrative processes. Despite this emerging relevance, the CBL has received comparatively less attention in aging research, which has focused mainly on other central nervous system (CNS) regions such as the neocortex and hippocampus. This review synthesizes the current evidence on glial cell aging across the CNS, emphasizing how cerebellar circuits follow distinct trajectories in terms of cellular remodeling, transcriptional reprogramming, and structural vulnerability. Recent findings highlight that cerebellar astrocytes and microglia exhibit specific signatures related to aging compared to their cortical counterpart, including moderate reactivity, selective immune response, and spatial reorganization. Cerebellar white matter (WM) undergoes structural alteration, suggesting that oligodendroglial cells may undergo region-specific alterations, particularly within WM tracts, although these aspects remain underexplored. Despite the presence of glial remodeling, the CBL maintains a notable degree of structural and functional integrity during aging. This resilience may be the result of the CBL’s ability to maintain synaptic adaptability and homeostatic balance, supported by its highly organized and compartmentalized architecture. A better understanding of the dynamics of cerebellar glial cells in aging may provide new insight into the mechanisms of brain maintenance and identify potential biomarkers for healthy brain aging. Full article

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

Background/Objectives: Successful discourse relies not only on linguistic but also on prosodic information. Difficulty recognizing emotion conveyed through prosody (receptive affective aprosodia) following right hemisphere stroke (RHS) significantly disrupts communication participation and personal relationships. Growing evidence suggests that damage to white matter in addition to gray matter structures impairs affective prosody recognition. The current study investigates lesion–symptom associations in receptive affective aprosodia during RHS recovery by assessing whether disruptions in distinct white matter structures impact different underlying affective prosody recognition skills. Methods: Twenty-eight adults with RHS underwent neuroimaging and behavioral testing at acute, subacute, and chronic timepoints. Fifty-seven healthy matched controls completed the same behavioral testing, which comprised tasks targeting affective prosody recognition and underlying perceptual, cognitive, and linguistic skills. Linear mixed-effects models and multivariable linear regression were used to assess behavioral performance recovery and lesion–symptom associations. Results: Controls outperformed RHS participants on behavioral tasks earlier in recovery, and RHS participants’ affective prosody recognition significantly improved from acute to chronic testing. Affective prosody and emotional facial expression recognition were affected by external capsule and inferior fronto-occipital fasciculus lesions while sagittal stratum lesions impacted prosodic feature recognition. Accessing semantic representations of emotions implicated the superior longitudinal fasciculus. Conclusions: These findings replicate previously observed associations between right white matter tracts and affective prosody recognition and further identify lesion–symptom associations of underlying prosodic recognition skills throughout recovery. Investigation into prosody’s behavioral components and how they are affected by injury can help further intervention development and planning. Full article

Background/Objectives: Despite extensive research, the underlying causes of amyotrophic lateral sclerosis (ALS) remain unclear. This umbrella review aims to synthesize a vast body of evidence from advanced magnetic resonance imaging (MRI) studies of ALS, encompassing a wide range of neuroimaging techniques and patient cohorts. Methods: Following the PRISMA guidelines, we conducted an extensive search of four databases (PubMed, Scopus, Web of Science, and Embase) for articles published until 3 December 2024. Data extraction and quality assessment were independently performed using the AMSTAR2 tool. Results: This review included 18 studies that incorporated data from over 29,000 ALS patients. Structural MRI consistently showed gray matter atrophy in the motor and extra-motor regions, with significant white matter (WM) atrophy in the corticospinal tract and corpus callosum. Magnetic resonance spectroscopy revealed metabolic disruptions, including reduced N-acetylaspartate and elevated choline levels. Functional MRI studies have demonstrated altered brain activation patterns and functional connectivity, reflecting compensatory mechanisms and neurodegeneration. fMRI also demonstrated disrupted motor network connectivity and alterations in the default mode network. Diffusion MRI highlighted microstructural changes, particularly reduced fractional anisotropy in the WM tracts. Susceptibility-weighted imaging and quantitative susceptibility mapping revealed iron accumulation in the motor cortex and non-motor regions. Perfusion MRI indicated hypoperfusion in regions associated with cognitive impairment. Conclusions: Multiparametric MRI consistently highlights widespread structural, functional, and metabolic changes in ALS, reflecting neurodegeneration and compensatory mechanisms. Full article

Background: The arcuate fasciculus (AF) is a critical white matter (WM) tract that connects key cortical language-processing regions, including the so-called Broca’s and Wernicke’s areas. The aim of the present study was to quantitatively assess its radiological–anatomical–morphometric modifications according to different brain tumor histotypes. Methods: A retrospective multicentric Italian study was conducted. AF reconstructions were calculated for both hemispheres for each patient diagnosed with glioblastoma (GBM), low-grade glioma (LGG), brain metastasis, and meningioma using Elements Fibertracking 2.0 software (Brainlab AG, Munich, Germany). A 3D object of each fascicle was evaluated for its volume, average fractional anisotropy (FA), and length. The cerebral healthy hemisphere was compared to the pathological contralateral in different tumor histotypes. Results: In total, 1294 patients were evaluated. A total of 156 met the inclusion criteria. We found a significant difference between healthy hemisphere and the contralateral for AF mean length and volume (p = 0.01 and p < 0.001, respectively). Considering separately the different tumor histotypes, the GBM subgroup (98, 63%) confirmed the results for mean FA and volume (p-value < 0.001); LGG patients (26, 17%) showed no significant difference between healthy and pathological hemisphere for AF mean length, mean FA, and volume (p-value 0.5, p-value 0.3, p-value <0.1, respectively). In patients affected by brain metastasis (18, 12%), Student’s t-test showed a significant difference for FA (p-value 0.003). No differences were found in patients affected by meningiomas (14, 9%) (14). Conclusions: Thorough knowledge of the microscopic anatomy and function of the arcuate fasciculus, as well as the pattern of growth of the different brain tumor histotypes, along with a careful preoperative neuroradiological assessment are mandatory to plan a tailored surgical strategy and perform a safe and effective surgical technique. The AF could be displaced and infiltrated/destructed by the solid component and peritumoral edema, respectively, of GBM. LGG shows a prevalent infiltrative pattern. Metastases account for AF dislocation due to peritumoral edema. Meningiomas do not affect WM anatomy. Full article

Childhood trauma encompasses various subtypes, and evidence suggests that neurodevelopmental damage differs across these subtypes. However, the specific impact of childhood emotional neglect (CEN), a distinct subtype of childhood trauma, on the microstructural integrity of brain white matter remains unclear. Therefore, the present study aims to investigate the effects of CEN on the microstructure of brain white matter in young adults using diffusion tensor imaging. After administering online questionnaires, conducting interviews, and obtaining diagnoses from specialized physicians, we recruited 20 young adults with a history of CEN and 20 young adults with no history of childhood trauma. Using automating fiber tract quantification (driven by a diffusion tensor model), we traced the 20 primary white matter fibers and divided each fiber into 100 nodes for analysis. Group differences in fractional anisotropy (FA) at each node of each fiber were then examined. The results revealed that the FA values at nodes 1–35 of the right thalamic radiation were consistently lower in the emotional neglect group compared to the control group (after FEW correction, cluster threshold = 22, p-threshold = 0.005). These findings suggest an association between CEN and reduced FA values in the right thalamic radiation, indicating alterations in brain white matter. Overall, our results contribute to the theoretical understanding of how “experience shapes the brain,” providing new insights into the neurostructural consequences of childhood emotional neglect. Full article

Glioblastoma (GBM) often exhibits distinct anatomical patterns of relapse after radiotherapy. Tumour cell migration along myelinated white matter tracts is a key driver of disease progression. The failure of conventional imaging to capture subclinical infiltration has driven interest in advanced imaging biomarkers capable of quantifying tumour–brain interactions. Diffusion tensor imaging (DTI), radiomics, and connectomics represent a triad of innovative, non-invasive approaches that map white matter architecture, predict recurrence risk, and inform biologically guided treatment strategies. This review examines the biological rationale and clinical applications of DTI-based metrics, radiomic signatures, and tractography-informed connectomics in GBM. We discuss the integration of these modalities into machine learning frameworks and radiotherapy/surgical planning, supported by landmark studies and multi-institutional data. The implications for personalised neuro-oncology are profound, marking a shift towards risk-adaptive, tract-aware treatment strategies that may improve local control and preserve neurocognitive function. Full article

Environmental justice research in the United States (US) documents greater air pollution exposures for Hispanic/Latino vs. non-Hispanic White groups. EJ research has not focused on the intersection of race/ethnicity and older age nor short-term fine particulate matter (PM_2.5) exposures. We address these knowledge gaps by studying US metropolitan area census tracts within 100 km of the US–Mexico border, a region with serious air quality issues. We use US Census American Community Survey data to construct sociodemographic variables and Environmental Protection Agency Downscaler data to construct long-term and short-term measures of PM_2.5 exposure. Using multivariable generalized estimating equations, we test for differences in PM_2.5 exposures between census tracts with higher vs. lower proportions of older Hispanic/Latino residents and older non-Hispanic White residents. The results indicate that as the proportion of the Hispanic/Latino population ≥ 65 years of age increases, long-term and short-term PM_2.5 exposures significantly increase. In contrast, as the proportion of the non-Hispanic White population ≥ 65 years of age increases, changes in long-term and short-term PM_2.5 exposures are statistically non-significant. These findings illuminate how race/ethnicity and older age intersect in shaping PM_2.5 exposure disparities and may inform efforts to mitigate air pollution exposures for overburdened people along the US–Mexico border. Full article

Purpose: Obesity’s metabolic consequences are well documented; however, its neurobiological underpinnings remain elusive. This systematic review addresses a critical gap by synthesizing evidence on obesity-induced neuroplasticity across structural, functional, and molecular domains through advanced neuroimaging. Methods: According to PRISMA guidelines, we systematically searched (2015–2024) across PubMed/Web of Science, employing MeSH terms: (“Obesity” [Majr]) AND (“Neuroimaging” [Mesh] OR “Magnetic Resonance Imaging” [Mesh]). A total of 104 studies met the inclusion criteria. The inclusion criteria required the following: (1) multimodal imaging protocols (structural MRI/diffusion tensor imaging/resting-state functional magnetic resonance imaging (fMRI)/positron emission tomography (PET)); (2) pre-/post-intervention longitudinal design. Risk of bias was assessed via the Newcastle-Ottawa Scale. Key Findings: 1. Structural alterations: 7.2% mean gray matter reduction in prefrontal cortex (Cohen’s d = 0.81). White matter integrity decline (FA reduction β = −0.33, p < 0.001) across 12 major tracts. 2. Functional connectivity: Resting-state hyperactivity in mesolimbic pathways (fALFF + 23%, p-FDR < 0.05). Impaired fronto–striatal connectivity (r = −0.58 with BMI, 95% CI [−0.67, −0.49]). 3. Interventional reversibility: Bariatric surgery restored prefrontal activation (Δ = +18% vs. controls, p = 0.002). Neurostimulation (transcranial direct current stimulation (tDCS) enhanced cognitive control (post-treatment β = 0.42, p = 0.009). Conclusion: 1. Obesity induces multidomain neural reorganization beyond traditional reward circuits. 2. Neuroimaging biomarkers (e.g., striatal PET-dopamine binding potential) predict intervention outcomes (AUC = 0.79). 3. Precision neuromodulation requires tripartite integration of structural guidance, functional monitoring, and molecular profiling. Findings highlight neuroimaging’s pivotal role in developing stage-specific therapeutic strategies. Full article

Mesenchymal progenitor cells (MPC) are effective in reducing tissue loss, preserving white matter, and improving forelimb function after a spinal cord injury (SCI). We proposed that by preconditioning the mouse by the intravenous delivery (IV) of MPCs for 24 h following SCI, this would provide a more favorable tissue milieu for an NSC intraspinal bridging transplantation at day three and day seven. In combination, these transplants will provide better anatomical and functional outcomes. The intravenous MSCs would provide cell protection and reduce inflammation. NSCs would provide a tissue bridge for axonal regeneration and myelination and reconnect long tract spinal pathways. Results showed that initial protection of the injury site by IV MPCs transplantation resulted in no increased survival of the NSCs transplanted at day seven. However, integration of transplanted NSCs was increased at the day three timepoint, indicating MPCs influence very early immune signaling. We show, in this study, that MPC transplantation resulted in a co-operative NSC cell survival improvement on day three post-SCI. In addition to increased NSC survival on day three, there was an increase in NSC-derived mature oligodendrocytes at this early timepoint. An in vitro analysis confirmed MPC-driven oligodendrocyte differentiation, which was statistically increased when compared to control NSC-only cultures. These observations provide important information about the combination, delivery, and timing of two cellular therapies in treating SCI. This study provides important new data on understanding the MPC inflammatory signaling within the host tissue and timepoints for cellular transplantation survival and oligodendroglia differentiation. These results demonstrate that MPC transplantation can alter the therapeutic window for intraspinal transplantation by controlling both the circulating inflammatory response and local tissue milieu. Full article

Mirror movements (MMs) are related to structural alterations of the pyramidal tract or transcallosal pathways, as well as functional impairment of the interhemispheric inhibitory effects on motor planning skills, leading to the inability to perform limb movements independently. On the other hand, white matter bundles that connect distant cortical regions are thought to be the anatomical substrate of seizure propagation in epileptic subjects, and the spread of excitation through intracortical and transcallosal pathways is a well-recognized pathophysiological abnormality in epilepsies. To investigate this possible association, we searched the MEDLINE and Embase electronic databases, and only original articles were considered eligible for inclusion; we found thirteen patients from eleven articles, all of them case study reports. Therefore, epilepsy and MM co-morbidity has rarely been reported in the same subjects, even if changes in interhemispheric modulation are shared by both conditions. However, the study of this co-morbidity may help in elucidating the exact pathophysiological mechanisms of MMs and to better understand the pathological interhemispheric connections in epilepsy patients. Full article

Maximal safe surgical resection is the gold standard in brain tumor surgery. Fluorescence-guided surgery (FGS) is one of many intraoperative techniques that have been designed with the intention of accomplishing this goal. 5-aminolevulinic acid (5-ALA) is one of the main fluorophores that facilitates FGS in neurosurgical oncology. Multiple different types of brain tumors can take in and metabolize 5-ALA into protoporphyrin IX (PpIX) through the mitochondria heme biosynthesis pathway. PpIX then selectively accumulates in brain tumor cells due to decreased ferrochelatase activity and emits red fluorescence (630–720 nm) when excited with blue light (375–440 nm). This mechanism allows neurosurgeons to better visualize tumor burden and increase extent of resection while preserving non-cancerous brain parenchyma and, specifically, eloquent white matter tracts, if combined with mapping techniques, thereby minimizing morbidity while improving survival. While 5-ALA use is well established in the treatment of high-grade gliomas, its applicability in recurrent high-grade and non-enhancing IDH-mutant low-grade gliomas, as well as non-glial tumors, is less established or limited by certain features of their cellular and molecular biology. This review aims to discuss the current landscape of 5-ALA utility across the diverse range of brain tumors, practical considerations that optimize its current use in neurosurgery, modern clinical limitations of 5-ALA, and how its application can be expanded by combining its use with other techniques that overcome current limitations. Full article

Background/Objectives: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo tractography to attain a deeper understanding of the subcortical connectivity and organization. Methods: Ten cerebral hemispheres were used in this study for white matter dissection according to Klingler’s technique. Measurements of different cortical structures and interhemispheric symmetry were compared. Diffusion tensor imaging sequences from twenty-five healthy individuals from the Human Connectome Project dataset were used to explore the connectivity of the olfactory system using DSI Studio. White matter connectivity between the following were reconstructed in vivo: (1) Olfactory bulb to primary olfactory cortices; (2) Olfactory bulb to secondary olfactory cortices; (3) Primary to secondary olfactory cortices. The DTI metrics of the identified major associative, projection and commissural pathways were subsequently correlated with olfactory function and cognition in seventy-five healthy individuals with Spearman’s rank correlation and the Benjamini–Hochberg method for false discoveries (CI 95%, p < 0.05) using R. Results: 1. The dissection showed that the lateral stria was significantly longer on the left side and projected towards the amygdala, the entorhinal and piriform cortex. 2. The medial stria was not evident as a consistent white matter structure. 3. Both dissection and tractography showed that major associative white matter pathways such as the uncinate fasciculus, the inferior fronto-occipital fasciculus and cingulum supported the connectivity between olfactory areas together with the anterior commissure. 4. No significant correlation was found between DTI metrics and sensory or cognition test results. Conclusions: We present the first combined fiber dissection analysis and tractography of the olfactory system. We propose a novel definition where the primary olfactory network is defined by the olfactory tract/bulb and primary olfactory cortices through the lateral stria only. The uncinate fasciculus, inferior fronto-occipital fasciculus and cingulum are the associative pathways supporting the connectivity between primary and secondary olfactory areas together with the anterior commissure. We suggest considering these structures as a secondary olfactory network. Further work is needed to attain a deeper understanding of the pathological and physiological implications of the olfactory system. Full article

Background/Objectives: Cerebral palsy (CP), often caused by early brain injury such as perinatal stroke or hemorrhage, is the most common lifelong motor disability. Early identification of at-risk infants and timely access to rehabilitation interventions are essential for improving long-term outcomes. The General Movements Assessment (GMA), performed in the first months of life, has high sensitivity and specificity to predict CP; however, the neurological correlates of general movements remain unclear. This analysis aimed to investigate the relationship between white matter integrity and general movements in infants with perinatal brain injury using advanced neuroimaging techniques. Methods: Diffusion-weighted MRI data were analyzed in 17 infants, 12 with perinatal brain injury and 5 typically developing infants. Tractography was used to identify the corticospinal tract, a key motor pathway often affected by perinatal brain injury, and tract-based spatial statistics (TBSS) were used to examine broader white matter networks. Diffusion parameters from the diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models were compared between infants with and without typical general movements. Results: Corticospinal tract integrity did not differ between groups when averaged across hemispheres. However, infants with asymmetric general movements exhibited greater corticospinal tract asymmetries. A subset of infants with atypical general movement trajectories at <6 weeks and 3–5 months of age showed reduced corticospinal tract integrity compared to those with typical general movements. TBSS revealed significant differences in white matter integrity between infants with typical and atypical general movements in several white matter pathways, including the corpus callosum, the right posterior corona radiata, bilateral posterior thalamic radiations, the left fornix/stria terminalis, and bilateral tapetum. Conclusions: These findings support and expand upon previous research suggesting that white matter integrity across multiple brain regions plays a role in the formation of general movements. Corticospinal integrity alone was not strongly associated with general movements; interhemispheric and cortical-subcortical connectivity appear critical. These findings underscore the need for further research in larger, diverse populations to refine early biomarkers of neurodevelopmental impairment and guide targeted interventions. Full article

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent, heterogeneous neurodevelopmental disorder. Methods: This study presents, for the first time, a comprehensive investigation of white matter microstructural differences between familial ADHD (ADHD-F) and non-familial ADHD (ADHD-NF) using advanced diffusion tensor imaging analyses in a large community-based sample. Results: Children with ADHD-F exhibited significantly greater volume in the right anterior thalamic radiations and the left inferior fronto-occipital fasciculus compared to controls, and greater volume in the left inferior longitudinal fasciculus relative to ADHD-NF. The ADHD-NF group showed reduced fractional anisotropy in the left inferior longitudinal fasciculus compared to the controls. In both the ADHD-F and ADHD-NF groups, a greater volume of anterior thalamic radiation significantly contributed to reduced ADHD symptoms. Conclusions: Our findings suggest that white matter microstructural alterations along the frontal-thalamic pathways may play a critical role in hereditary factors among children with ADHD-F and significantly contribute to elevated inattentive and hyperactive/impulsive behaviors in the affected children. Full article