Gray Matter Differences Research Articles

Long-term evolution of white and gray matter structural properties in migraine.

To elucidate the specific brain changes linked to clinical diagnoses and distinct temporal progression in migraine. Gray (GM) and white matter (WM) differences were previously identified in chronic migraine (CM) compared to episodic migraine (EM). Regarding GM, patients with CM showed increased cortical thickness in the inferior temporal gyrus, and reduced surface area in the precuneus cortex, superior frontal and temporal gyri, and supramarginal gyrus. In the WM, widespread reduced axial and mean diffusivity have been observed in patients with CM in tracts such as the middle cerebellar peduncle, the internal capsule, the corticospinal tract, and the sagittal stratum. However, no longitudinal studies with a long follow-up have been conducted to comprehend how those differences evolve over an extended period, in relation to the clinical evolution of the disease. A longitudinal study with a cohort design was conducted. Brain T1- and diffusion-weighted magnetic resonance imaging data were acquired in patients with migraine at two different timepoints, the first between May 2015 and July 2018, and the second between November 2021 and February 2022. Three WM descriptors and four GM morphometry parameters were extracted. Next, longitudinal changes were analyzed using generalized linear mixed models, after considering three different clinical groups: patients with a stable diagnosis (CM or EM) at both timepoints (24 CM, 31 EM), and 24 patients with CM who improved to EM. Different patterns of structural longitudinal changes were found depending on the clinical evolution. Regarding GM, patients with stable EM showed a longitudinal cortical thickness increase in the parietal and temporal cortex (annual relative change between 0.38% and 0.52% in five regions, adjusted p between 0.013 and 0.017), and the postcentral gyrus (annual relative change of 0.37%, adjusted p = 0.014). Patients with stable CM and EM showed a longitudinal cortical thickness decrease in the posterior cingulate gyrus (annual relative change of 0.51%, adjusted p = 0.027, and 0.34%, adjusted-p = 0.019, respectively), and patients who improved from CM to EM showed no changes (corrected p > 0.05). Moreover, regarding WM, the patients with stable EM showed a longitudinal increase in fractional anisotropy in the cerebral peduncle (annual relative change of 0.24%, adjusted p = 0.014). Differences in clinical evolution are linked to distinct patterns of structural changes, suggesting a heterogeneous impact of disease evolution on brain structure. Patients with CM who improved to EM showed no significant GM differences while those with longitudinally stable diagnoses showed cortical thickness maladaptation in pain processing-related regions and adaptation in other regions associated with migraine. Patients who improved from CM to EM showed an opposite longitudinal trend in large WM regions compared to stable patients, possibly as an adaptation to a distinct entity.

The subcortical correlates of self-reported sleep quality.

To assess the association between self-reported measures of sleep quality and cortical and subcortical local morphometry. Sleep quality, operationalized with the Pittsburgh Sleep Quality Index (PSQI), and neuroanatomical data from the full release of the young adult Human Connectome Project dataset were analyzed (N=1,112; 46% female; mean age: 28.8 years old). Local cortical and subcortical morphometry was measured with subject-specific segmentations resulting in voxelwise gray matter difference (i.e., voxel-based morphometry) measurements for cortex and local shape measurements for subcortical regions. Associations between the total score of PSQI, two statistical groupings of its subcomponents (obtained with a principal component analysis), and their interaction with demographic (i.e., sex, age, handedness, years of education) and biometric (i.e., BMI) variables were assessed using a general linear model and a nonparametric permutation approach. Sleep quality-related variance was significantly associated with subcortical morphometry, particularly in the bilateral caudate, putamen, and left pallidum, where smaller shape measures correlated with worse sleep quality. Notably, these associations were independent of demographic and biometric factors. In contrast, cortical morphometry, along with additional subcortical sites, showed no direct associations with sleep quality but demonstrated interactions with demographic and biometric variables. This study reveals a specific link between self-reported sleep quality and subcortical morphometry, particularly within the striatum and pallidum, reinforcing the role of these regions in sleep regulation. These findings underscore the importance of considering subcortical morphology in sleep research and highlight potential neuromodulatory targets for sleep-related interventions.

Asymmetric brain atrophy in Huntington's disease: A postmortem MRI study.

BackgroundHuntington's disease is a progressive, autosomal dominant, neurodegenerative disease caused by a CAG repeat expansion in the HTT gene. Medium spiny neurons of the striatum are especially vulnerable to the disease, and atrophy of the caudate and putamen can be documented by neuroimaging years before the onset of symptoms.ObjectiveIn this study, we aimed to characterize region-specific gray and white matter differences between Huntington's disease patients and controls.MethodsWe conducted a postmortem MRI study of the brains of 15 adults diagnosed with symptomatic Huntington's disease and 26 control subjects, aiming to compare the differences in regional grey and white matter volumes between the two groups.ResultsThe study revealed decreased volumes in both grey and white matter in patients with Huntington's disease, with the largest effect sizes observed in caudate and putamen. Notably, the atrophy predominantly affected the left hemisphere, particularly impacting grey and white matter regions adjacent to the pars opercularis, precentral, supramarginal, and pars orbitalis gyri, and the lateral orbitofrontal cortex. In the control group, asymmetry stems from larger left hemisphere regions compared to right, whereas an opposite pattern is observed in the Huntington's disease group.ConclusionsThese results suggest progressive, diffuse, and asymmetric grey and white matter atrophy occurs in Huntington's disease. The reasons for this asymmetry remain unknown; however, our study provides a more detailed characterization of previously reported grey and white matter changes in Huntington's disease, as observed through postmortem histopathological and MRI studies.

Age-dependent brain subcortical white and gray matter disruptions in patients with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric condition that can develop after experiencing a traumatic event, and it is associated with a range of functional and structural brain abnormalities. This study aimed to investigate agerelated differences in subcortical gray and white matter in veterans with PTSD. This study recruited 44 patients with PTSD and 48 healthy controls. Participants were divided into two age groups to evaluate structural magnetic resonance imaging analysis. The results showed that individuals with PTSD had significantly smaller subcortical gray matter volumes, including the bilateral thalamus, hippocampus, amygdala, left pallidum, and right accumbens-area (P<0.05). Diffusion tensor imaging (DTI) analyses revealed lower fractional anisotropy in several white matter structures, including the anterior limb of the internal capsule, anterior corona radiata, and cingulum in both hemispheres (P<0.05). Additionally, the mean diffusivity was higher in the anterior limb of the internal capsule, anterior corona radiata and the right external capsule (P<0.05). A comparative analysis between two age groups, over 50 and under 50 years old, showed that younger PTSD patients had a reduction in volume and abnormality in the corresponding white matter in more regions compared to the control group. These findings suggest that PTSD is associated with significant structural alterations in the brain, which may contribute to the pathophysiology of the disorder. So, patient age is an effective factor in exposure to traumatic events and an older age is continuously associated with a worsening traumatic brain injury outcome.

Cerebrovascular reactivity differences in healthy cerebral gray and white matter

AbstractPurposeTo quantify the speed and magnitude of cerebrovascular reactivity (CVR) metrics in hemispheric gray and white matter.MethodsA standardized isoxic hypercapnic cerebrovascular stimulus was administered using an automated arterial gas targeting system while monitoring blood oxygen–level dependent MRI. The correlation between the blood oxygen–level dependent signal and end‐tidal partial pressure of carbon dioxide were measured over time, enabling calculation of CVR metrics including the magnitude and speed (TAU) of the vascular response. The average CVR magnitude and TAU metrics were obtained from 50 healthy participants in the following regions: anterior, middle, and posterior cerebral artery (ACA, MCA, PCA) territory gray matter, the striatum, the thalamus, and hemispheric white matter.ResultsThe average MCA CVR is 17.39% greater than ACA CVR (95% confidence interval [CI]: 3.50, 31.28), and the average PCA CVR is 43.03% (95% CI: 29.13, 56.91) and 21.84% (95% CI: 10.00, 33.68) greater than ACA CVR and MCA CVR, respectively. The average TAU in the six regions were ACA = 29.5 ± 9.7 s, MCA = 29.4 ± 8.7 s, PCA = 28.6 ± 10.2 s, striatum = 30.5 ± 8.9 s, thalamus = 25.7 ± 10.0 s, and white matter = 46.3 ± 6.9 s. TAU was similar among all regions investigated except for the white matter, which was approximately 60% slower than the other regions (p &lt; 0.0001).ConclusionIn healthy individuals, there are significant differences in CVR metrics among the ACA, MCA, PCA gray‐matter vascular territories, thalamus, striatum, and hemispheric white matter. Future investigations of CVR should consider the presence of regional variability in CVR metrics when comparing healthy and diseased populations.

Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes.

Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) and dementia. We examined whether an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer's, or vascular dementia, and investigated whether differences in potentially modifiable lifestyle factors in the mid- to late-life period may attenuate this risk. A prospective cohort study of 365 782 participants free from dementia for at least 5 years after baseline assessment was conducted within the UK Biobank cohort. Genetic risk was assessed using a genomewide polygenic risk score (PRS) for CAD and lifestyle risk using a modified version of the American Heart Association's Life's Essential 8 Lifestyle Risk Score (LRS). Higher values for both scores were deemed to represent increased risk. Primary outcomes were incident all-cause, Alzheimer's, and vascular dementia diagnoses obtained from self-report and electronic health records. Secondary outcomes were neuroimaging phenotypes measured in 32 028 participants recalled for magnetic resonance imaging. Sensitivity analyses were conducted to test the extent by which biological and behavioral risk factors contributed to observed associations. A total of 8870 cases of all-cause dementia were observed over a median 13.9-year follow-up. Both genetic (PRS) and lifestyle (LRS) risk scores for CAD were associated with a modestly elevated risk of all-cause dementia (subhazard ratio per SD increase, 1.10 [1.08, 1.12], P<0.001, for PRS and 1.04 [1.02, 1.06], P=0.006, for LRS). This risk appeared largely attributable to underlying vascular dementia diagnoses (subhazard ratio, 1.16 [1.11, 1.21], P<0.001 for PRS and 1.15 [1.09, 1.22], P<0.001, for LRS), because Alzheimer's disease was found to demonstrate moderate associations with PRS alone (subhazard ratio, 1.09 [1.06, 1.13]; P<0.001). LRS was found to have an additive rather than interactive effect with PRS, with individuals in the highest tertiles for both genetic and lifestyle risk for CAD ≈70% more likely to develop vascular dementia during follow-up compared with those in the lowest tertiles for both (subhazard ratio, 1.71 [1.39, 2.11]; P<0.001). This was substantially attenuated in those with a low LRS at baseline, however, regardless of underlying genetic risk (30% reduction for low versus high LRS tertile regardless of PRS tertile; P<0.001 for all). In a subset of individuals recalled for neuroimaging assessments, those in the highest tertiles for genetic and lifestyle risk for CAD demonstrated a ≈25% greater volume of white matter hyperintensities than those in the lowest risk tertiles, but showed little difference in gray matter or hippocampal volumes. Sensitivity analyses identified associations between both biological and behavioral risk scores with white matter hyperintensity burden and vascular dementia, whereas some Alzheimer's dementia associations showed seemingly paradoxical relationships. Individuals who are genetically predisposed to developing CAD also face an increased risk of developing dementia in old age. This risk is reduced in those demonstrating healthy lifestyle profiles earlier in the lifespan, particularly in those who may be at an increased risk of developing dementia caused by an underlying vascular pathology.

Grey matter volume differences in pediatric obsessive–compulsive disorder: a meta-analysis of voxel-based morphometry studies

BackgroundObsessive–compulsive disorder (OCD) is one of the most commonly seen mental disorders onset from childhood. The neural mechanisms underlying OCD development and maintenance remain poorly understood. Various empirical evidence from structural magnetic resonance imaging (MRI) studies has reported structural differences in grey matter (GM) among pediatric OCD patients. However, some of the findings diverge from others, and the association between GM and individual differences in pediatric OCD remains inconclusive. To address this gap, we conducted a meta-analysis to synthesize findings quantitatively.MethodsThe current research conducted a quantitative meta-analysis of voxel-based GM studies to elucidate existence of neural correlates in pediatric OCD. A whole brain-based d-mapping approach was utilized to explore GM changes and further analyze the relationship between GM and individual differences in pediatric OCD patients.ResultsThirteen studies were included with 288 patients and 273 controls. Compared with controls, pediatric OCD demonstrated significantly greater GM volume in the left insula (SDM value = 1.72, p < 0.005) and left superior frontal gyrus (SFG) (orbital part) (SDM value = 1.47, p < 0.005), whereas we showed lower GM volume in the right superior temporal gyrus (STG) (SDM value = -1.87, p < 0.005), left inferior parietal gyri (IPG) (SDM value = -1.60, p < 0.005), left middle occipital gyrus (MOG) (SDM value = -1.66, p < 0.005), and left inferior frontal gyrus (IFG) (SDM value = -1.69, p < 0.005). The increase in SFG (orbital part) and decrease IPG was commonly found in those without psychiatric comorbidities and treatment-naive subgroup. Meta-regression analysis revealed that longer OCD duration was associated with less GM volume in IPG (SDM value = -3.057, p < 0.005). Finally, the onset age and the OCD symptoms severity were positively associated with GM volume in the SFG (SDM z = 2.387, p < 0.005).ConclusionsOur findings confirmed the most consistent GM differences in pediatric OCD, particularly in the MOG, IPG and SFG (orbital part), suggesting they are potential markers in pediatric OCD. Larger SFG (orbital part) and smaller IPG volumes are specific to those without comorbidities and untreated patients. The duration of OCD, symptom severity and onset age also influence GM structure. This research provides evidence of the underlying neuroanatomical characteristics of pediatric OCD.Trial registrationPROSPERO CRD42024601906.

Structural Cerebellar and Lateral Frontoparietal Networks are altered in CUD: An SBM Analysis.

Repetitive drug use results in enduring structural and functional changes in the brain. Addiction research has consistently revealed significant modifications in key brain networks related to reward, habit, salience, executive function, memory and self-regulation. Techniques like Voxel-based Morphometry have highlighted large-scale structural differences in grey matter across distinct groups. Source-based Morphometry (SBM) takes this a step further by incorporating the Independent Component Analysis to detect shared patterns of grey matter variation, all without requiring prior selection of regions of interest. However, SBM has yet to be employed in the study of structural alteration patterns related to cocaine addiction. Therefore, we performed this analysis to explore alterations in structural covariance specific to cocaine addiction. Our study involved 40 individuals diagnosed with Cocaine Use Disorder (CUD) and 40 matched healthy controls. Participants with CUD completed clinical questionnaires assessing the severity of their dependence and other relevant clinical variables. Following the adjustment for age-related effects, we observed notable disparities between groups in two structural independent components, which we identified as the structural cerebellar network and the structural lateral frontoparietal network, which display opposing trends. Specifically, the individuals with CUD exhibited a heightened contribution to the cerebellar network but simultaneously demonstrated a reduced contribution to the lateral frontoparietal network compared to the healthy controls. These findings unveil distinctive covariance patterns of neuroregulation linked with cocaine addiction, which indicates an interruption in the typical structural development in an affected lateral frontoparietal network, while suggesting an extended pattern of neuroregulation within the cerebellar network in individuals with CUD.

The subcortical correlates of self-reported sleep quality.

To assess the association between self-reported measures of sleep quality and cortical and subcortical local morphometry. Sleep quality, operationalized with the Pittsburgh Sleep Quality Index (PSQI), and neuroanatomical data from the full release of the young adult Human Connectome Project dataset were analyzed (N=1,112; 46% female; mean age: 28.8 years old). Local cortical and subcortical morphometry was measured with subject-specific segmentations resulting in voxelwise gray matter difference (i.e., voxel based morephometry) measurements for cortex and local shape measurements for subcortical regions. Associations between the total score of PSQI, two statistical groupings of its subcomponents (obtained with a principal component analysis), and their interaction with demographic (i.e., sex, age, handedness, years of education) and biometric (i.e., BMI) variables were assessed using a general linear model and a nonparametric permutation approach. Sleep quality-related variance was significantly associated with subcortical morphometry, particularly in the bilateral caudate, putamen, and left pallidum, where smaller shape measures correlated with worse sleep quality. Notably, these associations were independent of demographic and biometric factors. In contrast, cortical morphometry, along with additional subcortical sites, showed no direct associations with sleep quality but demonstrated interactions with demographic and biometric variables. This study reveals a specific link between self-reported sleep quality and subcortical morphometry, particularly within the striatum and pallidum, reinforcing the role of these regions in sleep regulation. These findings underscore the importance of considering subcortical morphology in sleep research and highlight potential neuromodulatory targets for sleep-related interventions.

Structural Development of Speech Networks in Young Children.

Characterizing the structural development of the neural speech network in early childhood is important to understand speech acquisition. To investigate speech in the developing brain, 94 children aged 4-7-years-old were scanned using diffusion weighted imaging (DWI) magnetic resonance imaging (MRI). In order to increase sample size and performance variability, we included children who were diagnosed with attention-deficit hyperactivity disorder (ADHD) from a larger ongoing study. Additionally, each child completed the Syllable Repetition Task (SRT), a validated measure of phoneme articulation. The DWI data were modeled using restriction spectrum imaging (RSI) to measure restricted and hindered diffusion properties in both grey and white matter. Consequently, we analyzed the diffusion data using both whole brain analysis, and automated fiber quantification (AFQ) analysis to establish tract profiles for each of six fiber pathways thought to be important for supporting speech development. In the whole brain analysis, we found that SRT performance was associated with restricted diffusion in bilateral inferior frontal gyrus, pars opercularis , right pre-supplementary and supplementary motor area, and bilateral cerebellar grey matter ( p < .005). Age moderated these associations in left pars opercularis and frontal aslant tract (FAT). However, in both cases only the cerebellar findings survived a cluster correction. We also found associations between SRT performance and restricted diffusion in cortical association fiber pathways, especially left FAT, and in the cerebellar peduncles. Analyses using automated fiber quantification (AFQ) highlighted differences in high and low performing children along specific tract profiles, most notably in left but not right FAT, in bilateral SLFIII, and in the cerebellar peduncles. These findings suggest that individual differences in speech performance are reflected in structural grey and white matter differences as measured by restricted and hindered diffusion metrics, and offer important insights into developing brain networks supporting speech in very young children.

Relaxometry and contrast-free cerebral microvascular quantification using balanced steady-state free precession MR fingerprinting.

This study proposes a novel, contrast-free Magnetic Resonance Fingerprinting (MRF) method using balanced Steady-State Free Precession (bSSFP) sequences for the quantification of cerebral blood volume (CBV), vessel radius (R), and relaxometry parameters (T , T , T *) in the brain. The technique leverages the sensitivity of bSSFP sequences to intra-voxel frequency distributions in both transient and steady-state regimes. A dictionary-matching process is employed, using simulations of realistic mouse microvascular networks to generate the MRF dictionary. The method is validated through in silico and in vivo experiments on six healthy subjects, comparing results with standard MRF methods and literature values. The proposed method shows strong correlation and agreement with standard MRF methods for T and T values. High-resolution maps provide detailed visualizations of CBV and microvascular structures, highlighting differences in white matter (WM) and gray matter (GM) regions. The measured GM/WM ratio for CBV is 1.91, consistent with literature values. This contrast-free bSSFP-based MRF method offers an new approach for quantifying CBV, vessel radius, and relaxometry parameters. Further validation against DSC imaging and clinical studies in pathological conditions is warranted to confirm its clinical utility.

Gray and white matter differences in the medial temporal lobe in late-life depression: a multimodal PET-MRI investigation.

Late-life depression (LLD) is characterized by medial temporal lobe (MTL) abnormalities. Although gray matter (GM) and white matter (WM) differences in LLD have been reported, few studies have investigated them concurrently. Moreover, the impact of aetiological factors, such as neurodegenerative and cerebrovascular burden, on tissue differences remains elusive. This prospective cross-sectional study involved 72 participants, including 33 patients with LLD (mean age 72.2 years, 23 female) and 39 healthy controls (HCs) (mean age 70.6 years, 24 female), who underwent clinical and positron emission tomography (PET)-magnetic resonance imaging (MRI) assessments. High-resolution 3D T1-weighted and T2-weighted FLAIR images were used to assess MTL GM volumes and white matter hyperintensities (WMHs), a proxy for cerebrovascular burden. Diffusion kurtosis imaging metrics derived from multishell diffusion MRI data were analyzed to assess WM microstructure in the following MTL bundles reconstructed using constrained spherical deconvolution tractography: uncinate fasciculus, fornix, and cingulum. Standardized uptake value ratio of 18F-MK-6240 in the MTL was used to assess Alzheimer's disease (AD) type tau accumulation as a proxy for neurodegenerative burden. Compared to HCs, patients with LLD showed significantly lower bilateral MTL volumes and WM microstructural differences primarily in the uncinate fasciculi bilaterally and right fornix. In patients with LLD, higher vascular burden, but not tau, was associated with lower MTL volume and more pronounced WM differences. LLD was associated with both GM and WM differences in the MTL. Cerebrovascular disease, rather than AD type tau-mediated neurodegenerative processes, may contribute to brain tissue differences in LLD.

Hippocampal subfield volume differences between female-to-male transgender individuals with cross-sex hormone therapy and cisgender women.

The prevalence of female-to-male (FtM) transgender individuals has risen recently, yet the effects of cross-sex hormone therapy on volumetric differences in the hippocampal subfields remain poorly understood. This study aimed to evaluate the differences of gray matter (GM) volume, especially focusing on the hippocampal subfields, in FtM transgender individuals and premenopausal cisgender women. Seventeen FtM transgender individuals who had undergone hysterectomies and were receiving testosterone therapy before participating in this study, along with 20 premenopausal women, underwent a single session of T1-weighted magnetic resonance imaging (MRI). FtM transgender group had significantly higher free-testosterone (free-T) levels and lower estradiol levels compared with premenopausal women group (p < 0.001). In voxel-wise analysis, FtM transgender individuals showed significantly larger GM volumes in the caudate nucleus, hypothalamus, and thalamus compared with premenopausal women (p < 0.01, FWE-corrected). More specifically, the right hippocampal subiculum volume was larger in FtM transgender individuals (p < 0.05, Bonferroni-corrected), and these volumes were positively correlated with the free-T levels (r = 0.34, p = 0.04). This study revealed the specific hippocampal subfield volume differences in the testosterone-treated FtM transgender group when compared to cisgender premenopausal women group. These findings might help elucidate the morphological variation of the specific cerebral regions associated with testosterone therapy in FtM transgender individuals and contribute to our understanding of the effects of gender-affirming hormone treatments as well.

Specific structural changes in Parkinson's disease-related olfactory dysfunction compared to others forms of olfactory dysfunction.

ContextOlfactory dysfunction (OD) is a common early symptom of Parkinson’s disease (PD). However, OD is not specific to PD, as approximatively 20% of the general population exhibit different forms of OD. To use olfactory measures for early Parkinson screening, it is crucial to distinguish PD-related OD from Non-Parkinsonian OD (NPOD).Objectives and hypothesisThis study aimed to compare the structural changes associated with PD-related OD (n = 15) with NPOD (n = 15), focusing on gray matter volumes and white matter fiber integrity in chemosensory regions. We hypothesized that PD-related OD presents specific structural alterations in these regions.MethodsParticipants underwent a 3 T MRI scan, which included anatomical T1 and diffusion-weighted imaging. Gray and white matter integrity were assessed using both whole-brain analyses (voxel-based morphometry—VBM and tract-based spatial statistics—TBSS, respectively) and localized approaches, including regions of interest and tractography.ResultsPD patients exhibited significantly higher gray matter volume in the left insula using restricted regions-of-interest analyses, while no other significant gray or white matter differences were found between groups.ConclusionStructural imaging of the gray matter, particularly the insula, but not of white matter, differentiates PD-related OD from NPOD.

Neuroanatomical basis of language ability in an autism subgroup with moderate language deficits.

Children with autism spectrum disorder (ASD) are highly heterogenous in their language abilities. A number of studies have shown neural correlates of language deficits in children with ASD, but the underlying neuroanatomical foundation of early language deficits in ASD remains largely elusive. In this study, we analyzed MRI data from a cohort of Chinese children with ASD (n = 67) and typical development (TD, n = 37) aged 1.5 to 6.5 years. The ASD sample was classified into two subgroups based on the median of the language scores: ASD with moderate language deficits (ASDmoderate, n = 34) and ASD with severe language deficits (ASDsevere, n = 34). We tested the group differences in the brain volumes between TD and two ASD subgroups, and also examined the associations between cortical grey matter volume and language abilities in TD and ASD subgroups, separately. We observed significant group differences in grey matter and white matter volume, with post-hoc analyses specifically indicating significant differences between TD and ASDmoderate subgroup. Significant correlations between grey matter volume and language scores were observed exclusively within the ASDmoderate subgroup, including positive associations in the bilateral superior temporal gyrus, hippocampus, and left inferior parietal lobe, and negative correlations in the bilateral precuneus. These findings provide novel evidence for the neuroanatomical basis related to language ability in an ASD subgroup with moderate language deficits, and offer new insights into the heterogeneity of language deficits in children with ASD.

Sex differences in gray matter, white matter, and regional brain perfusion in young, healthy adults.

Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between gray and white matter or without assessing regional CBF. Thus fundamental sex differences in regional or whole brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total gray and white matter perfusion as well as regional gray matter perfusion. Adults 18-30 yr old (females = 22 and males = 26) were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by computational anatomy toolbox (CAT12) analysis in statistical parametric mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females = 62 ± 9 and males = 45 ± 10 mL/100 g/min, P < 0.001), gray matter (females = 75 ± 11 and males = 54 ± 12 mL/100 g/min, P < 0.001), and white matter (females = 44 ± 6 and males = 32 ± 7 mL/100 g/min, P < 0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14% to 66% higher. A second MRI approach (4-dimensional flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, gray, and white matter levels and across dozens of brain regions and offer new clarity into fundamental sex differences in global and regional CBF regulation before aging or pathology.NEW & NOTEWORTHY MRI used to measure cerebral blood flow (CBF) in gray matter, white matter, and 68 regions in healthy men and women. This study demonstrated that CBF is 40% higher in women, the highest sex difference reported, when controlling for numerous important clinical confounders like age, smoking, menstrual cycle, comorbidities, and medications.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

Background: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(-), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(-). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(-) (n = 123) in the left hippocampus and the left posterior insula (puncorr < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(-) (n = 102). These results remained significant after multiple comparisons (pFDR < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR > 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.

Sex-related variability of white matter tracts in the whole HCP cohort

Behavioral differences between men and women have been studied extensively, as have differences in brain anatomy. However, most studies have focused on differences in gray matter, while white matter has been much less studied. We conducted a comprehensive study of 77 deep white matter tracts to analyze their volumetric and microstructural variability between men and women in the full Human Connectome Project (HCP) cohort of 1065 healthy individuals aged 22–35 years. We found a significant difference in total brain volume between men and women (+ 12.6% in men), consistent with the literature. 16 tracts showed significant volumetric differences between men and women, one of which stood out due to a larger effect size: the corpus callosum genu, which was larger in women (+ 7.3% in women, p = 5.76 × 10–19). In addition, we found several differences in microstructural parameters between men and women, both using standard Diffusion Tensor Imaging (DTI) parameters and more complex microstructural parameters from the Neurite Orientation Dispersion and Density Imaging (NODDI) model, with the tracts showing the greatest differences belonging to motor (cortico-spinal tracts, cortico-cerebellar tracts) or limbic (cingulum, fornix, thalamo-temporal radiations) systems. These microstructural differences may be related to known behavioral differences between the sexes in timed motor performance, aggressiveness/impulsivity, and social cognition.

Cortical thickness differences between hearing and perinatally deaf cats using ultra-high field MRI

Cortical thickness differences between hearing and perinatally deaf cats using ultra-high field MRI

Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia.

Ovarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer's disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counseled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM showing women without the BRCAm had cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and bilateral salpingo-oophorectomy (BSO) noted changes in cognition. The present, cross-sectional study examined whole-brain differences in gray matter (GM) volume using high-resolution, quantitative magnetic resonance imaging in women with BRCAm and intact ovaries (BRCA-preBSO [study cohort with BRCA mutation prior to oophorectomy]; n = 9) and after surgery with (BSO + estradiol-based therapy [ERT]; n = 10) and without (BSO; n = 10) postsurgical estradiol hormone therapy compared with age-matched women (age-matched controls; n = 10) with their ovaries. The BRCA-preBSO and BSO groups showed significantly lower GM volume in the left medial temporal and frontal lobe structures. BSO + ERT exhibited few areas of lower GM volume compared with age-matched controls. Novel to this study, we also observed that all three BRCAm groups exhibited significantly higher GM volume compared with age-matched controls, suggesting continued plasticity. The present study provides evidence, through lower GM volume, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, postsurgical ERT seems to ameliorate GM losses.