Gray Matter Changes Research Articles

Anxiety in Parkinson's Disease Is Associated with Changes in Brain Structural Connectivity.

Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety. The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI). 108 non-demented PD patients with (n = 31) and without (n = 77) anxiety as defined by their score on the Parkinson Anxiety Scale participated. DTI was used to determine the fractional anisotropy (FA) and mean diffusivity (MD) in specific tracts within anxiety-related neuronal circuits. Mean FA and MD were compared between groups and correlated with the severity of anxiety adjusted by sex, center, Hoehn & Yahr stage, levodopa equivalent daily dosage, and Hamilton depression rating scale. Compared to patients without anxiety, PD patients with anxiety showed lower FA within the striato-orbitofrontal, striato-cingulate, cingulate-limbic, and caudate-thalamic tracts; higher FA within the striato-limbic and accumbens-thalamic tracts; higher MD within the striato-thalamic tract and lower MD within the striato-limbic tract. Anxiety in PD is associated with microstructural alterations in anxiety-related neuronal circuits within the WM. This result reinforces the view that PD-related anxiety is linked to structural alteration within the anxiety-related brain circuits.

Genetic risks of Alzheimer's by APOE and MAPT on cortical morphology in young healthy adults.

Genetic risk factors such as APOE ε4 and MAPT (rs242557) A allele are associated with amyloid and tau pathways and grey matter changes at both early and established stages of Alzheimer's disease, but their effects on cortical morphology in young healthy adults remain unclear. A total of 144 participants aged from 18 to 24 underwent 3T MRI and genotyping for APOE and MAPT to investigate unique impacts of these genetic risk factors in a cohort without significant comorbid conditions such as metabolic and cardiovascular diseases. We segmented the cerebral cortex into 68 regions and calculated the cortical area, thickness, curvature and folding index for each region. Then, we trained machine learning models to classify APOE and MAPT genotypes using these morphological features. In addition, we applied a growing hierarchical self-organizing maps algorithm, which clustered the 68 regions into 4 subgroups representing different morphological patterns. Then, we performed general linear model analyses to estimate the interaction between APOE and MAPT on cortical patterns. We found that the classifiers using all cortical features could accurately classify individuals carrying genetic risks of dementia outperforming each individual feature alone. APOE ε4 carriers had a more convoluted and thinner cortex across the cerebral cortex. A similar pattern was found in MAPT A allele carriers only in the regions that are vulnerable for early tau pathology. With the clustering analysis, we found a synergetic effect between APOE ε4 and MAPT A allele, i.e. carriers of both risk factors showed the most deviation of cortical pattern from the typical pattern of that cluster. Genetic risk factors of dementia by APOE ε4 and MAPT (rs242557) A allele were associated with variations of cortical morphology, which can be observed in young healthy adults more than 30 years before Alzheimer's pathology is likely to occur and 50 years before dementia symptoms may begin.

Brain structural changes in alternating hemiplegia of childhood using single-case voxel-based morphometry analysis.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by ATP1A3 mutations. Using voxel-based morphometry (VBM) analysis, we compared an AHC patient cohort with controls. Additionally, with single-case VBM analysis, we assessed the associations between clinical severity and brain volume in patients with AHC. To investigate structural brain changes in gray matter (GM) and white matter (WM) volumes between 9 patients with AHC and 20 age-matched controls, VBM analysis was performed using three-dimensional T1-weighted magnetic resonance imaging. Single-case VBM analysis was also performed on nine patients with AHC to investigate the associations between the respective volumes of GM/WM differences and the motor level, cognitive level, and status epilepticus severity in patients with AHC. Compared with controls, patients with AHC showed significant GM volume reductions in both hippocampi and diffuse cerebellum, and there were WM reductions in both cerebral hemispheres. In patients with AHC, cases with more motor dysfunction, the less GM/WM volume of cerebellum was shown. Three of the six cases with cognitive dysfunction showed a clear GM volume reduction in the insulae. Five of the six cases with status epilepticus showed the GM volume reduction in hippocampi. One case had severe status epilepticus without motor dysfunction and showed no cerebellar atrophy. With single-case VBM analysis, we could show the association between region-specific changes in brain volume and the severity of various clinical symptoms even in a small sample of subjects.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. Prospective. Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3, η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3, η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. 2 TECHNICAL EFFICACY: Stage 3.

Changes in brain structure in subjects with resistance to thyroid hormone due to THRB mutations

BackgroundBeing critical for brain development and neurocognitive function thyroid hormones may have an effect on behaviour and brain structure. Our exploratory study aimed to delineate the influence of mutations in the thyroid hormone receptor (TR) ß gene on brain structure.MethodsHigh-resolution 3D T1-weighted images were acquired in 21 patients with a resistance to thyroid hormone ß (RTHß) in comparison to 21 healthy matched-controls. Changes in grey and white matter, as well as cortical thickness were evaluated using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).ResultsRTHß patients showed elevated circulating fT4 & fT3 with normal TSH concentrations, whereas controls showed normal thyroid hormone levels. RTHß patients revealed significantly higher scores in a self-rating questionnaire for attention deficit hyperactivity disorder (ADHD). Imaging revealed alterations of the corticospinal tract, increased cortical thickness in bilateral superior parietal cortex and decreased grey matter volume in bilateral inferior temporal cortex and thalamus.ConclusionRTHb patients exhibited structural changes in multiple brain areas. Whether these structural changes are causally linked to the abnormal behavioral profile of RTHß which is similar to ADHD, remains to be determined.

Roadmap for Postnatal Brain Maturation: Changes in Gray and White Matter Composition during Development Measured by Fourier Transformed Infrared Microspectroscopy.

Key events in postnatal brain development, such as neuronal migration, synaptogenesis, and myelination, shape the adult brain. These events are reflected in changes in gray and white matter (GM and WM) occurring during this period. Therefore, precise knowledge of GM and WM composition in perinatal brain development is crucial to characterizing brain formation as well as the neurodevelopmental disruption observed in diseases such as autism and schizophrenia. In this study, we combined histochemical and immunohistochemical staining with biochemical and biophysical analyses using Fourier transform infrared (IR) microspectroscopy (μFTIR) to better understand the chemical changes during postnatal developmental myelination. For this purpose, we analyzed the GM and WM in the mouse brain and cerebellum (strain C57BL/6) from postnatal day 0 (P0) to day P28 and established presumed correlations between staining and IR data. IR spectra allowed the (i) quantification of lipid and protein content through the CH2/amide I ratio, (ii) determination of chemical characteristics of lipids, such as the presence of unsaturated bonds in the carbonate chain or carbonyls from ester groups in the polar head, and (iii) determination of the protein secondary structure (α-helix and intramolecular β-sheets). The results indicate that the increase in the CH2/amide I ratio calculated from the μFTIR data correlates well with lipid histochemical staining. IR data indicated a change in the lipid composition in WM since carbonyl and unsaturated olefinic groups do not increase when lipids accumulate during myelination. Our correlation analysis between IR data and immunohistochemical staining of myelin-associated proteins revealed that myelin oligodendrocyte protein correlated well with lipid accumulation, while myelin basic protein appeared before lipid modifications, which indicated that myelin-associated proteins and lipid deposition were not synchronic. These events were related to a decrease in the intramolecular β/α protein ratio. Our results indicate that lipids and proteins in WM substantially change their composition due to primary myelination, and according to results obtained from staining, these modifications are better described by lipid histochemical staining than by immunohistochemistry against myelin-related proteins. In conclusion, μFTIR can be a useful technique to study WM during perinatal development and provide detailed information about alterations in the chemical composition related to neurodevelopmental diseases.

Patterns of brain atrophy in recently-diagnosed relapsing-remitting multiple sclerosis.

Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM). RRMS patients (N = 354) underwent 3T structural MRI <6 months after diagnosis and 1-year follow-up, as part of the Scottish multicentre 'FutureMS' study. MRI data were processed using FreeSurfer to derive volumetrics, and FSL for VBM (grey matter (GM) only), to establish regional patterns of change in GM and normal-appearing white matter (NAWM) over time throughout the brain. Volumetric analyses showed a decrease over time (q<0.05) in bilateral cortical GM and NAWM, cerebellar GM, brainstem, amygdala, basal ganglia, hippocampus, accumbens, thalamus and ventral diencephalon. Additionally, NAWM and GM volume decreased respectively in the following cortical regions, frontal: 14 out of 26 regions and 16/26; temporal: 18/18 and 15/18; parietal: 14/14 and 11/14; occipital: 7/8 and 8/8. Left GM and NAWM asymmetry was observed in the frontal lobe. GM VBM analysis showed three major clusters of decrease over time: 1) temporal and subcortical areas, 2) cerebellum, 3) anterior cingulum and supplementary motor cortex; and four smaller clusters within the occipital lobe. Widespread GM and NAWM atrophy was observed in this large recently-diagnosed RRMS cohort, particularly in the brainstem, cerebellar GM, and subcortical and occipital-temporal regions; indicative of neurodegeneration across tissue types, and in accord with limited previous studies in early disease. Volumetric and VBM results emphasise different features of longitudinal lobar and loco-regional change, however identify consistent atrophy patterns across individuals. Atrophy measures targeted to specific brain regions may provide improved markers of neurodegeneration, and potential future imaging stratifiers and endpoints for clinical decision making and therapeutic trials.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.

Cortical grey matter changes, behavior and cognition in children with sleep disordered breathing.

This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non-snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral-based regions of interest were identified using the Desikan-Killiany atlas. Student's t-tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes.

Adenosine A2A receptor availability in cerebral gray and white matter of patients with Parkinson's disease

ObjectiveAtrophic changes in cerebral gray matter of patients with PD have been reported extensively. There is evidence suggesting an association between cortical gyrification changes and white matter abnormalities. Adenosine A2A receptors have been shown to be upregulated in cerebral white matter and on reactive astrocytes in preclinical models of neurodegenerative diseases. We, therefore, sought to investigate in vivo changes in A2A receptor availability in cerebral gray and white matter of PD patients and its association with gray matter atrophy. MethodsEighteen patients with PD without dyskinesia and seven healthy controls were enrolled for this study. Brain MRI and dynamic PET scan was acquired with [11C]TMSX radioligand which binds selectively to A2A receptors. FreeSurfer software was used to segment cerebral gray and white matter structures. The resulting masks were used to calculate region specific volumes and to derive distribution volume ratios (DVRs), after co-registration with PET images, for the quantification of specific [11C]TMSX binding. ResultsWe showed an increase in A2A receptor availability in frontal (P < 0.001) and parietal (P < 0.001) white matter and a decrease in occipital (P = 0.02) gray matter of PD patients as compared to healthy controls. A decrease in gray matter volume ratios was observed in frontal (P < 0.01), parietal (P < 0.001), temporal (P < 0.01) and occipital (P < 0.01) ROIs in patients with PD versus healthy controls. ConclusionsOur results suggest a role of A2A receptor-based signaling in the neurodegenerative changes seen in the cerebral gray and white matter of patients with PD.

Alterations of gut microbiota are associated with brain structural changes in the spectrum of Alzheimer's disease: the SILCODE study in Hainan cohort.

The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition interaction remains largely unknown. One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut-brain-cognition interactions. The abundance of Lachnospiraceae, Lachnospiracea_incertae_sedis, Fusicatenibacter, and Anaerobutyricum decreased with cognitive ability. Rikenellaceae, Odoribacteraceae, and Alistipes were specifically enriched in the CI group. Mediterraneibacter abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume (p = 0.0214, p = 0.0162) and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus. This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD.

Association of cerebellar volume with cognitive and motor function in adults with congenital heart disease

IntroductionPatients with congenital heart disease (CHD) are at risk for cognitive and motor function impairments, brain injury, and smaller total brain volumes. The specific vulnerability of the cerebellum and its role in cognitive and motor functions in adults with congenital heart disease is not well defined.MethodsForty-three patients with CHD and 53 controls between 18 and 32 years underwent brain magnetic resonance imaging and cognitive, executive (EF), and motor function assessment. Cerebellar volumes were obtained using EasyMeasure and SUIT Toolbox. Associations between cerebellar volumes and cognitive and motor function were calculated using linear models.ResultsGeneral cognitive and pure motor functions were lower in patients compared to controls (P < 0.05). Executive functions were within the normal range. While total cerebellar volumes and the anterior lobes were similar in patients and controls (P > 0.1), the posterior cerebellar lobe was smaller in patients with more complex CHD (P = 0.006). Smaller posterior cerebellar gray matter was not associated with cognitive functions. Smaller anterior cerebellar gray matter was not significantly related to motor functions (P > 0.1).ConclusionIn adults with CHD, cerebellar volume was largely unimpaired. Patients with more complex CHD may be vulnerable to changes in the posterior cerebellar gray matter. We found no significant contribution of cerebellar gray matter to cognitive and motor impairments. More advanced imaging techniques are necessary to clarify the contribution of the cerebellum to cognitive and motor functions.

Imaging the Human Brain on Oral Contraceptives

Oral contraceptives (OCs) are the most popular form of birth control in the United States and in European countries. However, little is known about the extent OCs affect the brain’s function and morphology, although it is known that endogenous sex hormones shape the brain across the life span. Here, we reviewed studies that investigated structural gray and white matter in women using OCs in comparison to naturally cycling women. We focused on neuroimaging methods used to quantify structural gray and white matter changes: structural (sMRI) and diffusion MRI (dMRI). Relatively few imaging studies have been performed to answer the question of the effect of OCs on brain architecture. Studies have reported morphometric abnormalities in whole brain, cortical, and subcortical gray and white matter with no consistent pattern. Rather, findings in gray and white matter seem to be dependent on whether women using OCs and naturally cycling women were split into groups (active/inactive intake phase vs. follicular/luteal phase). There is a lack of sMRI and dMRI studies in this field of research. However, current studies demonstrate that it is important to compare women according to the follicular and luteal phase, as well as the active and inactive intake phase of OCs. Future studies with standardized protocols and larger sample sizes will allow an in-depth characterization of the effect of OCs on the brain. Furthermore, longitudinal studies comparing naturally cycling women to women using OCs over time and at different life stages are of particular importance.

Cortical alterations after very preterm birth and the association with socio-emotional abilities from childhood to early adolescence.

Very preterm birth (VPT; <32weeks' gestation) leads to a situation where crucial steps of brain development occur in an abnormal ex utero environment, translating to vulnerable cortical and subcortical development. Associated with this atypical brain development, children and adolescents born VPT are at a high risk of socio-emotional difficulties. In the current study, we unravel developmental changes in cortical gray matter (GM) concentration in VPT and term-born controls aged 6-14years, together with their associations with socio-emotional abilities. T1-weighted images were used to estimate signal intensities of brain tissue types in a single voxel (GM, white matter, and cortico-spinal fluid) and extract GM concentration disentangled from the presence of partial volume effects (PVEs). General linear model analysis was used to compare groups. Socio-emotional abilities were assessed and associations with GM concentration were explored using univariate and multivariate analyses. The effects of prematurity were far-reaching, with intricated patterns of increases and decreases of GM concentration mainly in frontal, temporal, parietal, and cingular regions. Better socio-emotional abilities were associated with increased GM concentration in regions known to be involved in such process for both groups. Our findings suggest that the trajectory of brain development following VPT birth may be fundamentally distinctive and impact socio-emotional abilities.

The correlation between changes in gray matter microstructure and cerebral blood flow in Alzheimer's disease.

To investigate the relationship between changes in cerebral blood flow (CBF) and gray matter (GM) microstructure in Alzheimer's disease (AD) and mild cognitive impairment (MCI). A recruited cohort of 23 AD patients, 40 MCI patients, and 37 normal controls (NCs) underwent diffusional kurtosis imaging (DKI) for microstructure evaluation and pseudo-continuous arterial spin labeling (pCASL) for CBF assessment. We investigated the differences in diffusion- and perfusion-related parameters across the three groups, including CBF, mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA). These quantitative parameters were compared using volume-based analyses for the deep GM and surface-based analyses for the cortical GM. The correlation between CBF, diffusion parameters, and cognitive scores was assessed using Spearman coefficients, respectively. The diagnostic performance of different parameters was investigated with k-nearest neighbor (KNN) analysis, using fivefold cross-validation to generate the mean accuracy (mAcc), mean precision (mPre), and mean area under the curve (mAuc). In the cortical GM, CBF reduction primarily occurred in the parietal and temporal lobes. Microstructural abnormalities were predominantly noted in the parietal, temporal, and frontal lobes. In the deep GM, more regions showed DKI and CBF parametric changes at the MCI stage. MD showed most of the significant abnormalities among all the DKI metrics. The MD, FA, MK, and CBF values of many GM regions were significantly correlated with cognitive scores. In the whole sample, the MD, FA, and MK were associated with CBF in most evaluated regions, with lower CBF values associated with higher MD, lower FA, or lower MK values in the left occipital lobe, left frontal lobe, and right parietal lobe. CBF values performed best (mAuc = 0.876) for distinguishing the MCI from the NC group. Last, MD values performed best (mAuc = 0.939) for distinguishing the AD from the NC group. Gray matter microstructure and CBF are closely related in AD. Increased MD, decreased FA, and MK are accompanied by decreased blood perfusion throughout the AD course. Furthermore, CBF values are valuable for the predictive diagnosis of MCI and AD. GM microstructural changes are promising as novel neuroimaging biomarkers of AD.

Cerebrospinal fluid soluble TREM2 is associated with accelerated AD‐related longitudinal neurodegeneration in preclinical Alzheimer’s disease

AbstractBackgroundCerebrospinal fluid (CSF) concentration of soluble TREM2 (sTREM2), a potential biomarker for microglial activation, is associated with attenuated longitudinal neurodegeneration and cognitive decline in Alzheimer’s disease (AD), but data in early disease are lacking. This study’s purpose was to use longitudinal volumetric imaging to assess the association of sTREM2 with age‐ and preclinical AD‐related grey matter (GM) changes.MethodCognitively unimpaired participants (N = 384; amyloid‐positive N = 82) from the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin ADRC clinical core studies with baseline CSF biomarker and subsequent longitudinal T1‐weighted magnetic resonance imaging data were analyzed. CSF sTREM2 and phosphorylated‐tau181/amyloid‐beta1‐42 ratio (pTau/Aβ42) were measured using the NeuroToolKit panel of robust prototype assays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland). T1‐weighted images were longitudinally registered to intra‐subject templates and segmented to create 58 GM regions of interest (ROIs) via the CAT12 longitudinal segmentation pipeline. Linear mixed‐effects models (random participant intercepts and age slopes) testing a three‐way interaction between time‐varying age, sTREM2, and pTau/Aβ42 to predict regional grey matter changes with all potential two‐way interactions and simple effects (adjusted for gender, years of education, intracranial volume, and head coil) were tested. In the event of a non‐significant three‐way interaction, the three‐way interaction was dropped and the model was reinterpreted. Statistical significance was considered at p &lt; .05, uncorrected for multiple comparisons.ResultAge had a negative effect on regional GM volume across the brain and showed widespread interactions with pTau/Aβ42, indicative of accelerated decline with AD pathology. Negative three‐way interactions between sTREM2, pTau/Aβ42, and age were evident in the angular, supramarginal, lingual, and middle occipital gyri, predicting accelerated AD‐related longitudinal neurodegeneration with higher sTREM2 concentration. Negative two‐way interactions between pTau/Aβ42 and sTREM2 were evident in the supplementary motor cortex and superior frontal gyrus, indicating worse effects of AD‐pathology with higher sTREM2, regardless of age.ConclusionOverall, higher sTREM2 may be associated with accelerated AD‐related neurodegeneration over time in the context of preclinical AD, particularly in posterior ROIs. Higher sTREM2 and underlying microglial activation may denote individuals at higher risk of experiencing the deleterious effects of early AD pathology on the brain.

Multivariate prediction of long COVID headache in adolescents using gray matter structural MRI features.

Headache is among the most frequent symptoms after coronavirus disease 2019 (COVID-19), so-called long COVID syndrome. Although distinct brain changes have been reported in patients with long COVID, such reported brain changes have not been used for predictions and interpretations in a multivariate manner. In this study, we applied machine learning to assess whether individual adolescents with long COVID can be accurately distinguished from those with primary headaches. Twenty-three adolescents with long COVID headaches with the persistence of headache for at least 3 months and 23 age- and sex-matched adolescents with primary headaches (migraine, new daily persistent headache, and tension-type headache) were enrolled. Multivoxel pattern analysis (MVPA) was applied for disorder-specific predictions of headache etiology based on individual brain structural MRI. In addition, connectome-based predictive modeling (CPM) was also performed using a structural covariance network. MVPA correctly classified long COVID patients from primary headache patients, with an area under the curve of 0.73 (accuracy = 63.4%; permutation p = 0.001). The discriminating GM patterns exhibited lower classification weights for long COVID in the orbitofrontal and medial temporal lobes. The CPM using the structural covariance network achieved an area under the curve of 0.81 (accuracy = 69.5%; permutation p = 0.005). The edges that classified long COVID patients from primary headache were mainly comprising thalamic connections. The results suggest the potential value of structural MRI-based features for classifying long COVID headaches from primary headaches. The identified features suggest that the distinct gray matter changes in the orbitofrontal and medial temporal lobes occurring after COVID, as well as altered thalamic connectivity, are predictive of headache etiology.

Cocaine Destroys Gray Matter Brain Cells and Accelerates Brain Aging.

Introduction: Cocaine use disorder (CUD) is a substance use disorder characterized by a strong desire to obtain, consume, and misuse cocaine. Little is known about how cocaine affects the structure of the brain. In this study, we first investigated the anatomical brain changes in individuals with CUD compared to their matched healthy controls, and then explored whether these anatomical brain abnormalities contribute to considerably accelerated brain aging among this population. Methods: At the first stage, we used anatomical magnetic resonance imaging (MRI) data, voxel-based morphometry (VBM), and deformation-based morphometry techniques to uncover the morphological and macroscopic anatomical brain changes in 74 CUD patients compared to 62 age- and sex-matched healthy controls (HCs) obtained from the SUDMEX CONN dataset, the Mexican MRI dataset of patients with CUD. Then, we computed brain-predicted age difference (i.e., brain-PAD: the brain-predicted age minus the actual age) in CUD and HC groups using a robust brain age estimation framework. Using a multiple regression analysis, we also investigated the regional gray matter (GM) and white matter (WM) changes associated with the brain-PAD. Results: Using a whole-brain VBM analysis, we observed widespread gray matter atrophy in CUD patients located in the temporal lobe, frontal lobe, insula, middle frontal gyrus, superior frontal gyrus, rectal gyrus, and limbic lobe regions compared to the HCs. In contrast, we did not observe any swelling in the GM, changes in the WM, or local brain tissue atrophy or expansion between the CUD and HC groups. Furthermore, we found a significantly higher brain-PAD in CUD patients compared to matched HCs (mean difference = 2.62 years, Cohen's d = 0.54; t-test = 3.16, p = 0.002). The regression analysis showed significant negative changes in GM volume associated with brain-PAD in the CUD group, particularly in the limbic lobe, subcallosal gyrus, cingulate gyrus, and anterior cingulate regions. Discussion: The results of our investigation reveal that chronic cocaine use is linked to significant changes in gray matter, which hasten the process of structural brain aging in individuals who use the drug. These findings offer valuable insights into the impact of cocaine on the composition of the brain.

Brain volumes and white matter diffusion across the adult lifespan in temporal lobe epilepsy.

Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

Presymptomatic grey matter alterations in ALS kindreds: a computational neuroimaging study of asymptomatic C9orf72 and SOD1 mutation carriers

BackgroundThe characterisation of presymptomatic disease-burden patterns in asymptomatic mutation carriers has a dual academic and clinical relevance. The understanding of disease propagation mechanisms is of considerable conceptual interests, and defining the optimal time of pharmacological intervention is essential for improved clinical trial outcomes.MethodsIn a prospective, multimodal neuroimaging study, 22 asymptomatic C9orf72 GGGGCC hexanucleotide repeat carriers, 13 asymptomatic subjects with SOD1, and 54 “gene-negative” ALS kindreds were enrolled. Cortical and subcortical grey matter alterations were systematically appraised using volumetric, morphometric, vertex, and cortical thickness analyses. Using a Bayesian approach, the thalamus and amygdala were further parcellated into specific nuclei and the hippocampus was segmented into anatomically defined subfields.ResultsAsymptomatic GGGGCC hexanucleotide repeat carriers in C9orf72 exhibited early subcortical changes with the preferential involvement of the pulvinar and mediodorsal regions of the thalamus, as well as the lateral aspect of the hippocampus. Volumetric approaches, morphometric methods, and vertex analyses were anatomically consistent in capturing focal subcortical changes in asymptomatic C9orf72 hexanucleotide repeat expansion carriers. SOD1 mutation carriers did not exhibit significant subcortical grey matter alterations. In our study, none of the two asymptomatic cohorts exhibited cortical grey matter alterations on either cortical thickness or morphometric analyses.DiscussionThe presymptomatic radiological signature of C9orf72 is associated with selective thalamic and focal hippocampal degeneration which may be readily detectable before cortical grey matter changes ensue. Our findings confirm selective subcortical grey matter involvement early in the course of C9orf72-associated neurodegeneration.