Search Results (223)

In recent years, research has focused on biomarkers as key tools to predict clinical outcomes and guide therapeutic decisions in Multiple Sclerosis (MS). MicroRNAs (miRs)—small non-coding RNA molecules that regulate gene expression at the post-transcriptional level—have emerged as promising biomarkers in MS due to their accessibility in biological fluids. This study investigates the role of specific serum miRs mainly involved in immune response regulation as potential prognostic biomarkers in MS, focusing on young patients with recent diagnosis. The study had a prospective design, involving a cohort of patients followed in the Hub and Spoke MS network of Verona province. Fifty-one patients (33F) aged 18–40 years with recent MS diagnosis (≤2 years; 45 relapsing-remitting, 6 primary progressive) were consecutively enrolled. At baseline, serum samples were collected for miR analysis alongside clinical-demographic and MRI data, including T2 lesion volume, normalized brain volume (NBV), gray matter volume, white matter volume (WMV) calculated at baseline and annual percentage brain volume change (PBVC) and occurrence of new T2 or gadolinium-enhancing (Gd+) lesions on follow-up scans. Candidate miRs were chosen based on their potential biological role in MS pathogenesis reported in the literature. miRs assays were done using real-time PCR and expressed as a ratio relative to a normalizer (i.e., miR-425-5p). Levels of miR-34a-5p were significantly higher in patients with Gd+ lesions (p < 0.001) and correlated to lower NBV (rho = −0.454, p = 0.001) and WMV (rho = −0.494, p < 0.001). Conversely, miR-140-5p exhibited a protective effect against occurrence of new T2 or Gd+ lesions over time (HR 0.43; IC 95% 0.19–0.99; p = 0.048). Additionally, miR-30b-5p correlated directly with PBVC (adjusted rho = −0.646; p < 0.001). These findings support the potential of serum miR-34a-5p, miR-140-5p, and miR-30b-5p as markers of disease activity and progression in patients with recently diagnosed MS. Full article

After spinal cord injury, pathological changes predominantly proceed caudal to the site of injury. To what extent these changes contribute to abnormalities during regeneration is poorly understood. Here, we addressed this question with a low-thoracic compression injury mouse model. The total numbers of immunohistochemically stained neuronal and glial cell types in the lumbar spinal cord were stereologically determined 6 weeks after injury. We also investigated injured mice deficient in close homolog of L1 (CHL1), which had been reported to recover better after injury than their wild-type littermates. We here report that there were no differences between genotypes in uninjured animals. In both injured CHL1-deficient and wild-type littermates, gray and white matter volumes were decreased as compared with uninjured mice. Numbers of motoneurons and parvalbumin-expressing interneurons were also reduced in both genotypes. Numbers of interneurons in injured mutant mice were lower than in wild-type littermates. Whereas injury did not affect numbers of astrocytes and oligodendrocytes in the gray matter, numbers of microglia/macrophages were increased. In the mutant white matter, numbers of oligodendrocytes were reduced, with no changes in numbers of astrocytes and microglia. A loss of motoneurons and interneurons was observed in both genotypes, but loss of interneurons was more prominent in the absence of CHL1. We propose that, after injury, CHL1 deficiency causes deficits in structural outcome not seen after injury of wild-type mice. Full article

Objectives: Few studies have reported in vivo measurements of electron density (ED) and effective atomic number (Z_eff) in normal brain tissue. To address this gap, dual-energy computed tomography (DECT)-derived ED and Z_eff maps were used to characterize normal-appearing adult brain tissues, evaluate age-related changes, and investigate correlations with myelin partial volume (V_my) from synthetic magnetic resonance imaging (MRI). Materials and Methods: Thirty patients were retrospectively analyzed. The conventional computed tomography (CT) value (CT_conv), ED, Z_eff, and V_my were measured in the normal-appearing gray matter (GM) and white matter (WM) regions of interest. V_my and DECT-derived parameters were compared between WM and GM. Correlations between V_my and DECT parameters and between age and DECT parameters were analyzed. Results: V_my was significantly greater in WM than in GM, whereas CT_conv, ED, and Z_eff were significantly lower in WM than in GM (all p < 0.001). Z_eff exhibited a stronger negative correlation with V_my (ρ = −0.756) than CT_conv (ρ = −0.705) or ED (ρ = −0.491). ED exhibited weak to moderate negative correlations with age in nine of the 14 regions. In contrast, Z_eff exhibited weak to moderate positive correlations with age in nine of the 14 regions. CT_conv exhibited negligible to insignificant correlations with age: Conclusions: This study revealed distinct GM–WM differences in ED and Z_eff along with opposing age-related changes in these quantities. Therefore, myelin may have substantially contributed to the lower Z_eff observed in WM, which underlies the GM–WM contrast observed on non-contrast-enhanced CT. Full article

Long-term physical training is known to induce brain plasticity, yet how these neural adaptations evolve across different stages of training remains underexplored. This two-year longitudinal study investigated the stage-dependent effects of endurance running on brain structure and resting-state function in healthy college students. Thirty participants were recruited into three groups based on their endurance training level: high-level runners, moderate-level runners, and sedentary controls. All participants underwent baseline and two-year follow-up MRI scans, including T1-weighted structural imaging and resting-state fMRI. The results revealed that the high-level runners exhibited a significant increase in degree centrality (DC) in the left dorsolateral prefrontal cortex (DLPFC). In the moderate-level group, more widespread changes were observed, including increased gray matter volume (GMV) in bilateral prefrontal cortices, medial frontal regions, the right insula, the right putamen, and the right temporo-parieto-occipital junction, along with decreased GMV in the posterior cerebellum. Additionally, DC decreased in the left thalamus and increased in the right temporal lobe and bilateral DLPFC; the fractional amplitude of low-frequency fluctuations (fALFF) in the right precentral gyrus was also elevated. These brain regions are involved in executive control, sensorimotor integration, and motor coordination, which may suggest potential functional implications for cognitive and motor performance; however, such interpretations should be viewed cautiously given the modest sample size and study duration. No significant changes were found in the control group. These findings demonstrate that long-term endurance training induces distinct patterns of brain plasticity at different training stages, with more prominent and widespread changes occurring during earlier phases of training. Full article

We previously reported that the fathers of the Bien Hoa birth cohort in Vietnam showed altered brain regional gray matter volumes, as measured by magnetic resonance imaging, and social anxiety traits associated with perinatal dioxin exposure. In the present study, we aimed to compare gray matter volumes and social anxiety scale scores between dioxin-exposed fathers in Bien Hoa and unexposed controls in an unsprayed area. Fat-based bioassay-toxic equivalency levels in serum were used to indicate dioxin exposure in adulthood. Results indicated that the longer Bien Hoa residency group (≥30 years) exposed to dioxins during the perinatal period and early childhood showed higher gray matter volumes in the right and left temporal lobes than controls. However, no significant differences in temporal lobe gray matter volumes were found between the shorter Bien Hoa residency group (<30 years) and controls. Furthermore, the longer, but not shorter, Bien Hoa residency group showed higher social–emotional subscale scores than controls. Additionally, fat-based bioassay-toxic equivalency levels were inversely correlated with gray matter volumes in several right temporal gyri. These findings suggest biphasic life stage-dependent adverse effects of dioxin exposure: perinatal dioxin exposure increases gray matter volumes, especially in the temporal lobe, which leads to neurodevelopmental disorders with socio-emotional disturbances, whereas dioxin exposure after brain development decreases cortical gray matter volumes, possibly leading to cognitive dysfunction. Full article

Background/Objectives: Previous magnetic resonance imaging (MRI) investigations reported brain alterations in anorexia nervosa restricting type (AN-R); however, the number of existing structural neuroimaging studies in the developmental age is limited. Here, we analyzed the volumetric brain differences between adolescent patients with AN-R and control peers, and possible correlations between brain volumes and clinical features. Methods: The sample comprised 47 adolescent females with AN-R (mean age: 15.0 years, SD = 1.4) who underwent structural MRI within one month of admission to a tertiary care university hospital, and 39 typically developing controls matched for sex and age. The patients were clinically characterized by standardized interviews/questionnaires. Using the voxel-based morphometry (VBM) technique, possible significant volumetric brain differences between the two groups were analyzed. Moreover, correlations between altered brain regions and clinical (i.e., body mass index (BMI) and disease duration) or psychopathological variables were investigated. Results: An overall reduction in gray matter (GM) volume with a concomitant increase in cerebrospinal fluid (CSF) is observed in AN-R patients; these alterations correlate with a lower BMI. The reduction in GM volume affects the frontal and parietal regions involved in the cognitive processes that underlie and sustain the AN-R clinical features. Conclusions: These results add to the current knowledge of the AN-R pathophysiology and pave the way for the development of brain imaging biomarkers for AN in the developmental age. Full article

Purpose: Our understanding of the influence of preterm birth and related perinatal exposures on early brain development is limited, hampering personalized optimization of neuroprotective strategies. This study assesses the effect of gestational age (GA) at birth on brain volumes at term-equivalent age (TEA) in infants without overt brain injury born across the GA spectrum. Methods: A cohort of infants born across the GA spectrum (25–40 weeks’ gestation) underwent 3T brain MRI around TEA (40–46 weeks postmenstrual age). Eight brain regions, intracranial and total tissue volumes were segmented using MANTiS (morphologically adaptive neonatal tissue segmentation toolbox). Segmentations were visually quality-checked and excluded if segmentation failed. Absolute TEA volume in relation to GA was assessed using univariate and multivariate (correction for postmenstrual age) linear regression analysis. Statistical significance was set at p < 0.05. Post hoc scatter plots of brain volumes relative to intracranial volumes were created. Results: Fifty infants were included (mean GA = 35.0 [SD = 3.3, range = 25.7–40.1] weeks). A higher GA at birth was significantly related to lower cerebrospinal fluid (p = 0.004) and amygdala (p = 0.02) volumes; no significant relation was found between GA and other volumes. Post hoc analyses showed positive trends between GA and several brain structures, including total brain tissue, cortical gray matter, deep gray matter, hippocampus, cerebellum and brainstem volumes. Conclusions: Our results suggest that GA has an effect on TEA brain volumes that is independent of brain lesions, with lower GA being associated with smaller brain tissue volumes and significantly larger cerebrospinal fluid volume. Preterm birth and related exposures may thus affect early brain growth and contribute to neurodevelopmental challenges encountered by preterm-born children. Full article

Background and Objectives: The objective of this research is to make a comparative evaluation of the correlation between the volumetric examination of subcortical cerebral regions and white matter hyperintensities classified according to the Fazekas scoring system. Materials and Methods: A total of 236 cases with cranial MRI studies were retrospectively analyzed. This study included patients aged over 45 years who had white matter hyperintensities and who did not have a prior stroke diagnosis. White matter hyperintensities were evaluated in axial FLAIR images according to Fazekas’s grading scale. Patients with Fazekas 0 and 1 were grouped in group 1 and the patients with Fazekas 2 and 3 were grouped in group 2. MRI data processing and subcortical volumetric analyses were performed using the volBrain MRI brain volumetry system. Results: There were statistically significant differences between groups 1 and 2 in terms of cerebrospinal fluid total brain white and gray matter (p < 0.001), total brain white and gray matter (p = 0.009), total cerebrum (p < 0.001), accumbens (p < 0.001), thalamus (p < 0.001), frontal lobe (p < 0.001), parietal lobe (p < 0.001), and lateral ventricle (p < 0.001) volumes. Conclusions: Our study finds a strong link between white matter hyperintensity burden and brain atrophy. This includes volume reductions in total brain white and gray matter, frontal and parietal lobe atrophy, increased cerebrospinal fluid (CSF), and atrophy in specific brain regions such as the accumbens and thalamus. Full article

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy. Full article

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

The etiology of schizophrenia remains poorly understood. Although certain risk factors have been identified, effective preventive measures are still lacking. This study investigates potential preventive methods while focusing on the role of vitamin D and its status. The role of malnutrition in schizophrenia risk was first identified in studies on the Dutch Hunger Winter. Vitamin D deficiency was hypothesized as a contributing factor shortly thereafter. This review aims to explore the correlations between vitamin D deficiency at various life stages (maternal, neonatal, adult) and schizophrenia risk, as well as its effects on pharmacokinetics, neurobiology, bone health, and metabolic syndrome. The studies were retrieved from two indexed databases, PubMed and Web of Science, following PRISMA guidelines and included studies published between 2000 and 2024. No correlation was found between maternal vitamin D levels and schizophrenia in offspring while a positive correlation was observed between low neonatal vitamin D levels and schizophrenia in later life. Approximately half of the studies on adults reported mean vitamin D concentrations of below 20 ng/mL which were negatively correlated with gray matter volume and bone health while positively correlated with the prevalence of metabolic syndrome. Additionally, vitamin D levels were also found to correlate with antipsychotic drug concentrations. Full article

(1) Background: Evidence from non-human animal and spaceflight analog studies have suggested that traveling to outer space could have a significant impact on the structural properties of the hippocampus, a brain region within the medial temporal lobe that is critical for learning and memory. Here, we tested this hypothesis in a group of astronauts who participated in a six-month mission in the International Space Station (ISS). (2) Methods: We collected magnetic resonance imaging (MRI) scans from a sample of 17 (9 males, 8 females) astronauts before and after the ISS mission, and calculated percent gray matter volume changes in the whole hippocampus and its (anterior, body, and posterior) subregions in both hemispheres. (3) Following the six-month mission in the ISS, we found a significantly decreased volume in the whole left hippocampus; in addition, when looking at subregions separately, we detected a significantly decreased volume in the anterior subregion of the left hippocampus and the body subregion of the right hippocampus. We also found a significantly decreased volume in the whole right hippocampus of male astronauts as compared to female astronauts. (4) Conclusions: This study, providing the very first evidence of hippocampal volumetric changes in astronauts following a six-month mission to the ISS, could have significant implications for cognitive performance during future long-duration spaceflights. 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

Objective: Burning mouth syndrome (BMS) is a chronic and often debilitating orofacial pain condition characterized by a burning sensation in the oral mucosa without clear abnormal lesions. While its etiology is considered multifactorial, the underlying pathophysiology remains unclear. This narrative review aims to synthesize existing functional magnetic resonance imaging (fMRI) studies to shed light on the central neural mechanisms contributing to BMS. Methods: A focused electronic search was conducted across the PubMed and J-STAGE databases for relevant articles published in English from January 2000 to May 2025. The review prioritized studies investigating brain structure and function using fMRI in individuals with BMS. Results: Our synthesis of the literature consistently demonstrated that the brains of individuals with BMS exhibit augmented connectivity within the medial pain system and a diminished gray matter volume in the medial prefrontal cortex (mPFC). These findings suggest a crucial role for altered brain circuitry, particularly a reduction in the output of the basal ganglia dopamine system, in the experience of BMS pain. Conclusions: The consistent fMRI findings strongly indicate that BMS involves significant functional and structural brain alterations. The observed changes in the mPFC and its connections to the basal ganglia dopamine system highlight this pathway as a potential target for both pharmacological and non-pharmacological neurological interventions for individuals with BMS. Full article

Background/Objectives: T1-weighted magnetic resonance imaging (MRI) and the Montreal Cognitive Assessment are standard, efficient, and swift clinical and research tools used when interrogating cognitively impairing (CI) conditions, such as Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). However, the associations between gross cognitive impairment (CI) as compared to domain-specific functioning and underlying neuroanatomical correlates have not been investigated among individuals with early-onset Mild Cognitive Impairment (MCI) or Alzheimer’s disease (EOAD), who can benefit greatly from early diagnosis and intervention strategies. Methods: We analyzed T1-weighted MRIs and Montreal Cognitive Assessment (MoCA) scores from the ADNI database in individuals < 65 years old who were either cognitively normal (CN) or had MCI or EOAD. Gray matter volume (GMV) was estimated in voxel-based morphometry (VBM) and ROI-parcellation general linear models examining associations with individual MoCA scores after adjusting for demographic covariates. Results: Results from 120 subjects (44 CN, 62 MCI, and 14 EOAD), identified significant global but also individually distinct domain-specific topographical signatures spanning the temporal, parietal, limbic, occipital, frontal lobes, and cingulate gyri. Conclusions: The results highlight neural correlates of cognitive functioning in a sample of young patients representative of the AD continuum, in addition to studying the structural MRI and functional cognitive difference. Full article