Cortical Gray Matter Research Articles

Fronto-temporal cortical grey matter thickness and surface area in the at-risk mental state and recent-onset schizophrenia: a magnetic resonance imaging study

BackgroundStudies to date examining cortical thickness and surface area in young individuals At Risk Mental State (ARMS) of developing psychosis have revealed inconsistent findings, either reporting increased, decreased or no differences compared to mentally healthy individuals. The inconsistencies may be attributed to small sample sizes, varying age ranges, different ARMS identification criteria, lack of control for recreational substance use and antipsychotic pharmacotherapy, as well as different methods for deriving morphological brain measures.MethodsA surfaced-based approach was employed to calculate fronto-temporal cortical grey matter thickness and surface area derived from magnetic resonance imaging (MRI) data collected from 44 young antipsychotic-naïve ARMS individuals, 19 young people with recent onset schizophrenia, and 36 age-matched healthy volunteers. We conducted group comparisons of the morphological measures and explored their association with symptom severity, global and socio-occupational function levels, and the degree of alcohol and cannabis use in the ARMS group.ResultsGrey matter thickness and surface areas in ARMS individuals did not significantly differ from their age-matched healthy counterparts. However, reduced left-frontal grey matter thickness was correlated with greater symptom severity and lower function levels; the latter being also correlated with smaller left-frontal surface areas. ARMS individuals with more severe symptoms showed greater similarities to the recent onset schizophrenia group. The morphological measures in ARMS did not correlate with the lifetime level of alcohol or cannabis use.ConclusionsOur findings suggest that a decline in function levels and worsening mental state are associated with morphological changes in the left frontal cortex in ARMS but to a lesser extent than those seen in recent onset schizophrenia. Alcohol and cannabis use did not confound these findings. However, the cross-sectional nature of our study limits our ability to draw conclusions about the potential progressive nature of these morphological changes in ARMS.

Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants.

Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective. In 36 infants born <32 weeks' gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes. We compared outcomes between infants exposed to low (bottom tertile, range 0.06-0.13 mg/mL) vs. high (top tertile, range 0.22-0.35 mg/mL) lactoferrin using median regression in models adjusted for gestational age, birth weight z-score, sex, and postmenstrual age. Compared to infants exposed to low lactoferrin, infants exposed to high lactoferrin had 43.9 cc (95% CI: 7.6, 80.4) larger total brain volume, 48.3 cc (95% CI: 12.1, 84.6) larger cortical gray matter, and 3.8 cc (95% CI: 0.7, 7.0) larger deep gray matter volume at term equivalent age. Other regional brain volumes were not statistically different between groups. Higher lactoferrin exposure during the neonatal hospitalization was associated with larger total brain and gray matter volumes, suggesting that lactoferrin may have potential as a dietary supplement to enhance brain growth in the neonatal intensive care unit setting. This study suggests that lactoferrin, a whey protein found in human milk, may be beneficial for preterm infant brain development, and therefore has potential as a dietary supplement in the neonatal intensive care unit setting.

Hemispheric asymmetries in cortical grey matter of gyri and sulci in modern human populations from South America.

Structural asymmetries of brain regions associated with lateralised functions have been extensively studied. However, there are fewer morphometric analyses of asymmetries of the gyri and sulci of the entire cortex. The current study assessed cortical asymmetries in a sample of healthy adults (N = 175) from an admixed population from South America. Grey matter volume and surface area of 66 gyri and sulci were quantified on T1 magnetic resonance images. The departure from zero of the differences between left and right hemispheres (L-R), a measure of directional asymmetry (DA), the variance of L-R, and an index of fluctuating asymmetry (FA) were evaluated for each region. Significant departures from perfect symmetry were found for most cortical gyri and sulci. Regions showed leftward asymmetry at the population level in the frontal lobe and superior lateral parts of the parietal lobe. Rightward asymmetry was found in the inferior parietal, occipital, frontopolar, and orbital regions, and the cingulate (anterior, middle, and posterior-ventral). Despite this general pattern, several sulci showed the opposite DA compared to the neighbouring gyri, which remarks the need to consider the neurobiological differences in gyral and sulcal development in the study of structural asymmetries. The results also confirm the absence of DA in most parts of the inferior frontal gyrus and the precentral region. This study contributes with data on populations underrepresented in the databases used in neurosciences. Among its findings, there is agreement with previous results obtained in populations of different ancestry and some discrepancies in the middle frontal and medial parietal regions. A significant DA not reported previously was found for the volume of long and short insular gyri and the central sulcus of the insula, frontomarginal, transverse frontopolar, paracentral, and middle and posterior parts of the cingulate gyrus and sulcus, gyrus rectus, occipital pole, and olfactory sulcus, as well as for the volume and area of the transverse collateral sulcus and suborbital sulcus. Also, several parcels displayed significant variability in the left-right differences, which can be partially attributable to developmental instability, a source of FA. Moreover, a few gyri and sulci displayed ideal FA with non-significant departures from perfect symmetry, such as subcentral and posterior cingulate gyri and sulci, inferior frontal and fusiform gyri, and the calcarine, transverse collateral, precentral, and orbital sulci. Overall, these results show that asymmetries are ubiquitous in the cerebral cortex.

Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T

GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml.Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively.Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus).Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1–-inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio.Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012).Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18–27 min (GABA+) and 9–18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

Altered brain function and structure in carpal tunnel syndrome: a systematic review and meta-analysis of structural and functional brain imaging.

This systematic review with a meta-analysis aimed to identify the altered brain structure and function in carpal tunnel syndrome (CTS) by summarizing the literature about magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) outcomes compared to healthy controls (HC). CTS is the most common nerve entrapment in the arm associated with altered peripheral and central nociceptive system. PRISMA guidelines were used to report the outcomes. Six databases were searched for relevant literature (Web of Science, Scopus, PubMed, Sage, EBSCO host, and Cochrane). Eligible studies comparing MRI, fMRI, and MEG findings in people with CTS (present for at least 2months) and HC through the following parameters: (1) interdigit cortical separation distance, (2) white and grey matter changes, (3) peak latency of M20 wave and recovery function of N20 from the somatosensory cortex (SI), and (4) surface area of activated digit cortical representation. The results from different studies were pooled and a meta-analysis was done. From 17 included, there was a significant reduction of interdigit cortical separation distance of index-middle and index-little fingers in the CTS (SMD = -0.869, 95% CI (-1.325, -0.413), p-value = 0.000) and (SMD = -0.79, 95% CI (-1.217, -0.364), p-value = 0.000), respectively. Middle-little fingers interdigit separation showed no difference (SMD = -0.2, 95% CI (-0.903, 1.309), p-value = 0.718). There is evidence supporting the altered brain structure and function in CTS as evidenced by reduction of interdigit cortical separation distance, and excessive blurring and disinhibition of SI, with low resting state functional connectivity. Thus, centrally directed therapeutic approaches might complement peripheral treatments.

Subcortical volumes and cognition in CADASIL – A pilot study

BackgroundCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) represents the most common heritable cause of vascular dementia. Subcortical volumes might be proxies of brain reserve capacity and reflective of cognitive function. We explored the impact of subcortical volumes on cognition in CADASIL patients. MethodsWe included 90 patients with pathogenic NOTCH3 variants from the Taiwan Associated Genetic and Nongenetic Small Vessel Disease cohort. They underwent MRI sessions at baseline. The volumes of the putamen, caudate, pallidum, thalamus, cerebellum, cortical gray matter and brain parenchymal fraction (BPF) were calculated by using FreeSurfer. We tested the association of the subcortical volumes, cortical gray matter volume and BPF with scores of the Mini-mental state examination (MMSE), cognitive domains, and the diagnosis of vascular cognitive impairment (VCI) which was defined as MMSE score <24. ResultsThe thalamus and putamen were consistently associated with the MMSE (thalamus adjusted beta per SD decrement -1.41 [95 % CI -2.68–(-0.14)], p = 0.03; R²=0.25; putamen -1.93 [95 % CI -2.99–(-0.86)], p < 0.001; R²=0.36) and VCI (thalamus OR per SD-decrement 3.66 [95 % CI 1.38–9.72], p = 0.009), putamen (OR 3.06 [95 % CI 1.21–7.73], p = 0.02). A larger thalamus volume was also associated with better executive function and visuospatial perception. The cortical gray matter volume and the BPF showed associations with various cognitive outcomes in all analyses. ConclusionAlthough cortical gray matter volume and the BPF still appear to be robust markers of cognitive performance in CADASIL, the volumes of the thalamus and the putamen might also be promising regions of interest for future research.

Reporting Psychiatric Disease Characteristics in Post-Mortem- and Biological Research.

Inflammation is a prominent hypothesis in the neurobiology of depression. In our transcriptomic profiling study of microglia in chronic major depressive disorder (MDD), we revealed a distinct disease-associated microglia (DAM) transcriptomic profile exclusively found in cortical gray matter, that we have designated DepDAM. These DepDAM revealed an immune-suppressed state, with a possible upstream mechanism for microglial suppression, by upregulation of CD200 and CD47 ("don't eat me signals") located on synapses. We extensively report on disease characteristics, such as cause of death, reason for euthanasia, and psychiatric state when deceased. When excluding MDD donors in a euthymic state, the trend of lower CD45 membrane expression on white matter microglia became significant, and the difference in gray matter microglia became larger. For Western blot analysis of CD47 and CD200, both means of the definitely depressed donor groups (MDD-D) increased. This underscores the utmost importance of reporting on patient and episode characteristics, such as severity, episode traits, (type of) suicidality, mode of decease, and state of illness at death in post-mortem- and biological psychiatric research. For psychiatric post-mortem research, we suggest using well-characterized donors (eg, after "psychological autopsy") selected by an experienced clinician.

Brain growth until adolescence after a neonatal focal injury: sex related differences beyond lesion effect.

Early focal brain injuries lead to long-term disabilities with frequent cognitive impairments, suggesting global dysfunction beyond the lesion. While plasticity of the immature brain promotes better learning, outcome variability across individuals is multifactorial. Males are more vulnerable to early injuries and neurodevelopmental disorders than females, but long-term sex differences in brain growth after an early focal lesion have not been described yet. With this MRI longitudinal morphometry study of brain development after a Neonatal Arterial Ischemic Stroke (NAIS), we searched for differences between males and females in the trajectories of ipsi- and contralesional gray matter growth in childhood and adolescence, while accounting for lesion characteristics. We relied on a longitudinal cohort (AVCnn) of patients with unilateral NAIS who underwent clinical and MRI assessments at ages 7 and 16 were compared to age-matched controls. Non-lesioned volumes of gray matter (hemispheres, lobes, regions, deep structures, cerebellum) were extracted from segmented T1 MRI images at 7 (Patients: 23 M, 16 F; Controls: 17 M, 18 F) and 16 (Patients: 18 M, 11 F; Controls: 16 M, 15 F). These volumes were analyzed using a Linear Mixed Model accounting for age, sex, and lesion characteristics. Whole hemisphere volumes were reduced at both ages in patients compared to controls (gray matter volume: -16% in males, -10% in females). In ipsilesional hemisphere, cortical gray matter and thalamic volume losses (average -13%) mostly depended on lesion severity, suggesting diaschisis, with minimal effect of patient sex. In the contralesional hemisphere however, we consistently found sex differences in gray matter volumes, as only male volumes were smaller than in male controls (average -7.5%), mostly in territories mirroring the contralateral lesion. Females did not significantly deviate from the typical trajectories of female controls. Similar sex differences were found in both cerebellar hemispheres. These results suggest sex-dependent growth trajectories after an early brain lesion with a contralesional growth deficit in males only. The similarity of patterns at ages 7 and 16 suggests that puberty has little effect on these trajectories, and that most of the deviation in males occurs in early childhood, in line with the well-described perinatal vulnerability of the male brain, and with no compensation thereafter.

Cerebral Small Vessel Disease Is Associated With Smaller Brain Volumes in Adults With Type 1 Diabetes.

Introduction: Type 1 diabetes has been linked to brain volume reductions as well as to cerebral small vessel disease (cSVD). This study concerns the relationship between normalized brain volumes (volume fractions) and cSVD, which has not been examined previously. Methods: We subjected brain magnetic resonance imaging studies of 187 adults of both sexes with Type 1 diabetes and 30 matched controls to volumetry and neuroradiological interpretation. Results: Participants with Type 1 diabetes had smaller thalami compared to controls without diabetes (p = 0.034). In subgroup analysis of the Type 1 diabetes group, having any sign of cSVD was associated with smaller cortical (p = 0.031) and deep gray matter volume fractions (p = 0.029), but a larger white matter volume fraction (p = 0.048). After correcting for age, the smaller putamen volume remained significant. Conclusions: We found smaller thalamus volume fractions in individuals with Type 1 diabetes as compared to those without diabetes, as well as reductions in brain volume fractions related to signs of cSVD in individuals with Type 1 diabetes.

Examining the relationship between anxiety and regional brain volumes in the National Alzheimer's Coordinating Center uniform, imaging, and biomarker datasets

Anxiety has been associated with a greater risk of Alzheimer's disease (AD). Existing research has identified structural differences in regional brain tissue in participants with anxiety, but results have been inconsistent. We sought to determine the association between anxiety and regional brain volumes, and the moderation effect of APOE ε4. Using data from participants in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set, with complete imaging (MRI) and biomarker data (n = 1533), multiple linear regression estimated the adjusted effect of anxiety on 30 structural MRI regions. The moderation effect of APOE ε4 on the relation between structural MRI regions and anxiety was assessed as was the moderation effect of cognitive status. False discovery rate was used to adjust for multiple comparisons. After controlling for intracranial volume, age, sex, years of education, race, Hispanic ethnicity, and cognitive status, seven MRI regions demonstrated lower volumes among participants with anxiety: total cerebrum gray matter volume, right hippocampus volume, hippocampal volume (total), right and left frontal lobe cortical gray matter volume, and right and total temporal lobe cortical gray matter volume. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions, with corresponding ventricular enlargement. Future research should investigate if anxiety-related changes to brain morphology contribute to greater AD risk.

Changes in cortical grey matter volume with Cognitive Orientation to daily Occupational Performance intervention in children with developmental coordination disorder.

Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive-based, task-specific intervention recommended for children with developmental coordination disorder (DCD). We recently showed structural and functional brain changes after CO-OP, including increased cerebellar grey matter. This study aimed to determine whether CO-OP intervention induced changes in cortical grey matter volume in children with DCD, and if these changes were associated with improvements in motor performance and movement quality. This study is part of a randomized waitlist-control trial (ClinicalTrials.gov ID: NCT02597751). Children with DCD (N = 78) were randomized to either a treatment or waitlist group and underwent three MRIs over 6 months. The treatment group received intervention (once weekly for 10 weeks) between the first and second scan; the waitlist group received intervention between the second and third scan. Cortical grey matter volume was measured using voxel-based morphometry (VBM). Behavioral outcome measures included the Performance Quality Rating Scale (PQRS) and Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). Of the 78 children, 58 were excluded (mostly due to insufficient data quality), leaving a final N = 20 for analyses. Due to the small sample size, we combined both groups to examine treatment effects. Cortical grey matter volume differences were assessed using a repeated measures ANOVA, controlling for total intracranial volume. Regression analyses examined the relationship of grey matter volume changes to BOT-2 (motor performance) and PQRS (movement quality). After CO-OP, children had significantly decreased grey matter in the right superior frontal gyrus and middle/posterior cingulate gyri. We found no significant associations of grey matter volume changes with PQRS or BOT-2 scores. Decreased cortical grey matter volume generally reflects greater brain maturity. Decreases in grey matter volume after CO-OP intervention were in regions associated with self-regulation and motor control, consistent with our other studies. Decreased grey matter volume may be due to focal increases in synaptic pruning, perhaps as a result of strengthening networks in the brain via the repeated learning and actions in therapy. Findings from this study add to the growing body of literature demonstrating positive neuroplastic changes in the brain after CO-OP intervention.

Multiple dural arteriovenous fistulas showing isolated subcortical white matter T2 hyperintensity with gadolinium enhancement

We describe a 44-year-old man with a complaint of atonic seizures of the left upper limb, followed by generalized seizures. Brain MRI showed isolated juxtacortical white matter T2 hyperintensity with gadolinium (Gd) enhancement of the adjacent cortical gray matter and subcortical white matter in the right frontal convexity. Treatment with levetiracetam was effective for seizure suppression, and he had no other neurological abnormalities. Human leukocyte antigen typing revealed B54 and Cw1, which indicated the possibility of neuro-Sweet disease. However, a general examination, which included vital signs and eye and skin findings, was normal. A cerebrospinal fluid test showed a mild elevation in protein levels without pleocytosis and a normal range of interleukin-6. Electroencephalography showed intermittent slow waves without epileptic discharge in the bilateral temporal lobes. We detected subtle flow voids in the pia mater of the left frontal lobe, which suggested cerebrovascular disease, and specifically, the possibility of dural arteriovenous fistulas. Computed tomography angiography showed abnormally dilated perimedullary veins in the left frontal lobe. Cerebral angiography confirmed the existence of four dural arteriovenous fistulas, which included two retrograde leptomeningeal venous drainages in the right frontal cortical veins supplied by the anterior branch of the right middle meningeal artery. The other dural arteriovenous fistulas were retrograde leptomeningeal venous drainages in the left frontal cortical veins supplied by the anterior and posterior convexity branches of the left middle meningeal artery. The patient underwent successful endovascular embolization of all dural arteriovenous fistulas with Onyx injection. A follow-up MRI showed gradual improvement of the T2 hyperintensity and Gd enhancement. He remained seizure-free for 2 years following endovascular embolization.

The added value of double inversion recovery (DIR) sequence compared to fluid attenuation inversion recovery (FLAIR) in identifying multiple sclerosis lesions and different cortical subtypes

Background. Diabetic here is a rising concern about multiple sclerosis (MS) lesions that occur in the cortical gray matter (GM), owing to its direct relationship with the disability and cognition dysfunction that occur during the MS course. Two magnetic resonance imaging (MRI) sequences that aid in the precise identification of these lesions are the Double Inversion Recovery (DIR) and Fluid Attenuation Inversion Recovery (FLAIR) sequences. Objective. To study the importance of the DIR for brain lesion detection and the various cortical subtypes distinction in MS-diagnosed patients and its correlations to the level of patient disability by comparing it to FLAIR. Patients and Methods: Thirty MS patients participated in this retrospective cross-sectional study, who had been previously diagnosed with MS and were routinely followed up at the Radiology Department at Ain-Shams University. Results. Comparing the DIR sequence to FLAIR, the overall MS lesion detection enhanced by 8% (p&lt;0.001). Regarding the detection of cortical lesion subtypes (I–IV), it was discovered that the DIR sequence revealed significantly more lesions than FLAIR (p&lt;0.001). The cortical lesions detected by DIR or FLAIR were found to have positive, highly significant correlations with both patients’ disability and the MS duration. Conclusion. For lesion identification, DIR is more effective than FLAIR, particularly for cortical and juxtacortical lesions in MS patients.

Comparison of brain volume measurements in methamphetamine use disorder with healthy individuals using volbrain method

Aim: This study aims to examine brain structures in individuals with methamphetamine use disorder (MUD) and to understand the possible effects of methamphetamine on these structures. Materials and Methods: The study was retrospectively evaluated in 21 MUD and 21 healthy controls. VolBrain segmentation method was used. Results: Grey Matter (GM), Cortical GM, Cerebrum total, and GM volumes were found to be less and significantly higher in MUD compared to healthy controls (p&amp;lt;0.01). Accumbens, Basal Forebrain, Caudate, Pallidum, Putamen, and Parietal Lobe volumes were increased in MUD (p&amp;lt;0.01). Amygdala, Hippocampus, Ventral Diencephalone, Frontal Lobe, Posterior Orbital Gyrus, Precentral Gyrus, Temporal Lobe, Calcarine Cortex, Middle Occipital Gyrus, Superior Occipital Gyrus, Limbic Cortex volumes were significantly smaller in MUD compared to healthy controls. Conclusion: This study helped us better understand MUD's effects on brain structures. It also provided important information for developing effective strategies for treating and preventing MUD.

Genetic evidence suggests a genetic association between major depressive disorder and reduced cortical gray matter volume: A Mendelian randomization study and mediation analysis

BackgroundSeveral studies have suggested an association between major depressive disorder (MDD) and abnormal brain structure. However, it is unclear whether MDD affects cortical gray matter volume, a common indicator of cognitive function. We aimed to determine whether MDD was associated with decreased cortical gray matter volume (GMV) through a Mendelian randomization (MR) study. MethodsWe obtained summary genetic data from a study conducted by the Psychiatric Genomics Consortium, which recruited a total of 480,359 participants (135,458 cases and 344,901 controls). Genetic tools—single nucleotide polymorphisms (SNPs)—of MDD were extracted from the study and their effects on gray matter volumes of the cortex and total brain were evaluated in a large cohort from the UK Biobank (n = 8427). The effects of the SNPs were pooled using inverse variance weighted (IVW) analysis and further tested in several sensitivity analyses. We tested whether C-reactive protein (CRP) levels and interleukin-6 signaling were the mediators of the effects using a multivariate MR model. ResultsThirty-three SNPs were identified and adopted as genetic tools for predicting MDD. IVW analysis showed that MDD was associated with lower overall GMV (beta value −0.106, 95%CI -0.188 to −0.023, p = 0.011) in the frontal pole (left frontal pole, −0.152, 95%CI -0.177 to −0.127, p = 0.013; right frontal pole, −0.133, 95%CI -0.253 to −0.013, p = 0.028). Multivariate and mediation analysis showed that interleukin-6 was an important mediator of GMV reduction. Reverse causality analysis found no evidence that total GMV affected the risk of MDD, but showed that increased left precuneus cortex volume and left posterior cingulate cortex volume were associated with increased risk of MDD. LimitationsPotential pleiotropic effects and overestimation of real-world effects. Key assumptions for MR analysis may not be satisfactorily met. ConclusionMDD was associated with a reduced GMV, and interleukin-6 might be a mediator of GMV reduction.

Sex differences in brain atrophy in dementia with Lewy bodies.

Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n=327; 73±8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n=165; 69±9 years, 72% males). We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

Cortical Thin Patch Fraction Reflects Disease Burden in MS: The Mosaic Approach.

GM pathology plays an essential role in MS disability progression, emphasizing the importance of neuroradiologic biomarkers to capture the heterogeneity of cortical disease burden. This study aimed to assess the validity of a patch-wise, individual interpretation of cortical thickness data to identify GM pathology, the "mosaic approach," which was previously suggested as a biomarker for assessing and localizing atrophy. We investigated the mosaic approach in a cohort of 501 patients with MS with respect to 89 internal and 651 external controls. The resulting metric of the mosaic approach is the so-called thin patch fraction, which is an estimate of overall cortical disease burden per patient. We evaluated the mosaic approach with respect to the following: 1) discrimination between patients with MS and controls, 2) classification between different MS phenotypes, and 3) association with established biomarkers reflecting MS disease burden, using general linear modeling. The thin patch fraction varied significantly between patients with MS and healthy controls and discriminated among MS phenotypes. Furthermore, the thin patch fraction was associated with disease burden, including the Expanded Disability Status Scale, cognitive and fatigue scores, and lesion volume. This study demonstrates the validity of the mosaic approach as a neuroradiologic biomarker in MS. The output of the mosaic approach, namely the thin patch fraction, is a candidate biomarker for assessing and localizing cortical GM pathology. The mosaic approach can furthermore enhance the development of a personalized cortical MS biomarker, given that the thin patch fraction provides a feature on which artificial intelligence methods can be trained. Most important, we showed the validity of the mosaic approach when referencing data with respect to external control MR imaging repositories.

Quantitative brain morphometry identifies cerebellar, cortical, and subcortical gray and white matter atrophy in late-onset Tay-Sachs disease.

Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.

White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Abstract Characterizing how, when, and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white matter microstructure, white matter macrostructure, and morphology of the cortex associated with white matter pathways. We analyzed four large, high-quality, cross-sectional datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways—describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological differences at different stages of the lifespan. Third, we show unique trajectories of age associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that are expected to be useful for studying normal and abnormal white matter development and degeneration.

Distance from main arteries influences microstructural and functional brain tissue characteristics

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ, and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing. All in all, this pilot study provides a novel insight on brain regionalisation based on artery distance, which merits further investigation to validate its biological underpinnings.