Gray Matter Volume Research Articles

CSF Parvalbumin Levels at Multiple Sclerosis Diagnosis Predict Future Worse Cognition, Physical Disability, Fatigue, and Gray Matter Damage.

Cognitive impairment (CI) in multiple sclerosis (MS) is frequent and determined by a complex interplay between inflammatory and neurodegenerative processes. We aimed to investigate whether CSF parvalbumin (PVALB), measured at the time of diagnosis, may have a prognostic role in patients with MS. In this cohort study, CSF analysis of PVALB and Nf-L levels was performed on all patients at diagnosis (T0) and combined with physical, cognitive, and MRI assessment after an average of 4 years of follow-up (T4) from diagnosis. Cognitive performance was evaluated with a comprehensive neuropsychologic battery: both global (cognitively normal, CN, mildly CI, mCI, and severely CI, sCI) and domain cognitive status (normal/impaired in memory, attention/information processing speed, and executive functions) were considered. Cortical thickness and gray matter volume data were acquired using 3T MRI scanner. A total of 72 patients with MS were included. At diagnosis, PVALB levels were higher in those patients who showed a worsening physical disability after 4 years of follow-up (p = 0.011). CSF PVALB levels were higher in sCI patients than in CN (p = 0.033). Moreover, higher PVALB levels significantly correlated with worse global cognitive (p = 0.024) and memory functioning (p = 0.044). A preliminary clinical threshold for PVALB levels at diagnosis was proposed (2.57 ng/mL), which maximizes the risk of showing CI (in particular, sCI) at follow-up, with a sensitivity of 91% (specificity 30%). No significant results were found for these associations with Nf-L. In addition, patients with higher levels of PVALB at diagnosis showed higher cognitive (p = 0.024) and global fatigue (p = 0.043) at follow-up. Finally, higher PVALB levels also correlated significantly with more pronounced CTh/volume at T4 in the inferior frontal gyrus (p = 0.044), postcentral gyrus (p = 0.025), frontal pole (p = 0.042), transverse temporal gyrus (p = 0.008), and cerebellar cortex (p = 0.041) and higher atrophy (change T0-T4) in the right thalamus (p = 0.038), pericalcarine cortex (p = 0.009), lingual gyrus (p = 0.045), and medial frontal gyrus (p = 0.028). The significant association found between parvalbumin levels in the CSF at diagnosis and cognitive, clinical, and neuroradiologic worsening after 4 years of follow-up support the idea that parvalbumin, in addition to Nf-L, might represent a new potential prognostic biomarker, reflecting MS neurodegenerative processes occurring since early disease stages.

Structural MRI findings in the brain related to pain distribution in chronic overlapping pain conditions: An explorative case-control study in females with fibromyalgia, temporomandibular disorder-related chronic pain and pain-free controls.

Few neuroimaging studies have investigated structural brain differences associated with variations in pain distribution. To explore structural differences of the brain in fibromyalgia (FM), temporomandibular disorder pain (TMD) and healthy pain-free controls (CON) using structural and diffusion MRI. A case-control exploratory study with three study groups with different pain distribution were recruited: FM (n = 16; mean age [standard deviation]: 44 [14] years), TMD (n = 17, 39 [14] years) and CON (n = 10, 37 [14] years). Participants were recruited at the University Dental Clinic in Malmö, Sweden. T1-weighted and diffusion MRIs were acquired, clinical and psychosocial measures were obtained. Main outcome measures were subcortical volume, cortical thickness, white matter microstructure and whole brain grey matter intensity. Patients with FM had smaller volume in the right thalamus than patients with TMD (p = .020) and CON (p = .030). The right thalamus volume was negatively correlated to pain intensity (r = -0.37, p = .022) and pain-related disability (r = -0.45, p = .004). The FM group had lower cortical thickness in the right anterior prefrontal cortex than CON (p = .005). Cortical thickness in this area was negatively correlated to pain intensity (r [37] = - 0.48, p = .002). This study suggests that thalamus grey matter alterations are associated with FM and TMD, and that anterior prefrontal cortex grey matter alterations are associated with FM but not TMD. Studies on chronic overlapping pain conditions are needed in relation to possible nociplastic pain mechanisms in the brain and central nervous system.

The effect of outdoor air pollution on Alzheimer’s disease: a systematic review

Abstract Air pollution is one of the largest global environmental risks to public health. Over recent years, neuroimaging techniques have started to uncover the detrimental impact air pollution has had on brain health, including the development of Alzheimer’s Diseases (AD). We systematically reviewed the literature to evaluate the effects of long-term exposure (months to years) to outdoor air pollutants on the development of AD-like neurology. This review was registered on PROSPERO (CRD42023482979) and followed PRISMA guidelines. Four large databases (MEDLINE, Embase, Scopus, and CINAHL) were searched in November 2023 using terms associated with air pollution, neuroimaging, and AD. Only peer-reviewed primary research articles using neuroimaging data to examine AD-like pathology after long-term exposure to air pollutants (Particulate Matter (PM2.5, PM10), SO2, NO2, O3, and/or CO) were included. Titles, abstracts and full-texts were screened, and included articles were quality assessed using the Newcastle Ottawa Scale. A narrative synthesis was conducted to analyse the studies. Our search yielded 397 results, of which eight articles met our inclusion criteria. Articles focused on changes to white matter (n = 5), cortical thickness (n = 6), and grey matter (n = 2). Exposure to PM2.5 was commonly associated with white matter reductions, and PM10 and NO2 exposure was associated with reduced cortical thickness. The effect of exposure to different outdoor pollution on grey matter was inconclusive, with both increases and decreases in grey matter volume observed. This review highlighted how PM2.5, PM10 and NO2 exposure was associated with neurological changes commonly seen in AD. These findings can be used by policymakers and researchers to identify specific pollutants that need greater restrictions and regulations to improve population health. Key messages • PM2.5, PM10 and NO2 exposure are associated with neurological changes commonly seen in AD. • Greater restrictions and regulations are needed on specific pollutants to improve population health.

Social-semantic knowledge in frontotemporal dementia and after anterior temporal lobe resection

Abstract Degraded semantic memory is a prominent feature of frontotemporal dementia (FTD). It is classically associated with semantic dementia and anterior temporal lobe (ATL) atrophy, but semantic knowledge can also be compromised in behavioural-variant FTD (bvFTD). Motivated by understanding behavioural change in FTD, recent research has focused selectively on social-semantic knowledge, with proposals that the right ATL is specialised for social concepts. Previous studies have assessed very different types of social concepts and have not compared performance to that on matched non-social concepts. Consequently, it remains unclear to what extent various social concepts are (i) concurrently impaired in FTD, (ii) distinct from general semantic memory and (iii) differentially supported by the left and right ATL. This study assessed multiple aspects of social-semantic knowledge and general conceptual knowledge across cohorts with ATL-damage arising from either neurodegeneration or resection. We assembled a test battery measuring knowledge of multiple types of social concept. Performance was compared to non-social general conceptual knowledge, measured using the Cambridge Semantic Memory Test Battery and other matched non-social-semantic tests. Our transdiagnostic approach included bvFTD, semantic dementia and “mixed” intermediate cases to capture the FTD clinical spectrum, as well as age-matched healthy controls. People with unilateral left or right ATL resection for temporal lobe epilepsy (TLE) were also recruited to assess how selective damage to the left or right ATL impacts social- and non-social-semantic knowledge. Social- and non-social-semantic deficits were severe and highly correlated in FTD. Much milder impairments were found after unilateral ATL resection, with no left vs. right differences in social-semantic knowledge or general semantic processing, and with only naming showing a greater deficit following left vs. right damage. A principal component analysis of all behavioural measures in the FTD cohort extracted three components, interpreted as capturing: (1) FTD severity, (2) semantic memory and (3) executive function. Social and non-social measures both loaded heavily on the same semantic memory component, and scores on this factor were uniquely associated with bilateral ATL grey matter volume but not with the degree of ATL asymmetry. Together, these findings demonstrate that both social- and non-social-semantic knowledge degrade in FTD (semantic dementia and bvFTD) following bilateral ATL atrophy. We propose that social-semantic knowledge is part of a broader conceptual system underpinned by a bilaterally-implemented, functionally-unitary semantic hub in the ATLs. Our results also highlight the value of a transdiagnostic approach for investigating the neuroanatomical underpinnings of cognitive deficits in FTD.

Integrated Analysis of Gut microbiome, Inflammation and Neuroimaging Features Supports the Role of Microbiome-Gut-Brain Crosstalk in Schizophrenia

Abstract Background and Hypothesis Gut microbiota has been implicated in the pathogenesis of schizophrenia (SZ) and relevant changes in the brain, but the underlying mechanism remains elusive. This study aims to investigate the microbiota-gut-brain crosstalk centered on peripheral inflammation in SZ patients. Study Design We recruited a cohort of 182 SZ patients and 120 healthy controls (HC). Multi-omics data, including fecal 16S rRNA, cytokine data, and neuroimaging data, were collected and synthesized for analysis. Multi-omics correlations and mediation analyses were utilized to determine the associations of gut microbiome with inflammatory cytokines and neuroimaging characteristics. Additionally, machine learning models for effective SZ diagnosis were separately generated based on gut microbial and neuroimaging data. Study Results Gut microbial dysbiosis, characterized by a decrease in butyrate-producing bacteria and an increase in pro-inflammatory bacteria, has been identified in SZ patients. These key microbial taxa were associated with increased inflammatory cytokines, potentially through mediating lipid metabolic pathways such as steroid biosynthesis and linoleic acid metabolism. Further analysis revealed altered microbial genera to be correlated with disrupted gray matter volume and regional homogeneity in SZ patients. Importantly, certain inflammatory cytokines mediated the relationship between the SZ-enriched genus Succinivibrio and aberrant activity of anterior cingulate cortex and left inferior temporal gyrus in the SZ group. Moreover, the classification model based on gut microbial data showed comparable efficacy to the model based on brain functional signatures in SZ diagnosis. Conclusions This study presents evidence for the dysregulated microbiota-gut-brain axis in SZ and emphasizes the central role of peripheral inflammation.

Predictive and Explainable Artificial Intelligence for Neuroimaging Applications

Background: The aim of this review is to highlight the new advance of predictive and explainable artificial intelligence for neuroimaging applications. Methods: Data came from 30 original studies in PubMed with the following search terms: “neuroimaging” (title) together with “machine learning” (title) or ”deep learning” (title). The 30 original studies were eligible according to the following criteria: the participants with the dependent variable of brain image or associated disease; the interventions/comparisons of artificial intelligence; the outcomes of accuracy, the area under the curve (AUC), and/or variable importance; the publication year of 2019 or later; and the publication language of English. Results: The performance outcomes reported were within 58–96 for accuracy (%), 66–97 for sensitivity (%), 76–98 for specificity (%), and 70–98 for the AUC (%). The support vector machine and the convolutional neural network registered the best performance (AUC 98%) for the classifications of low- vs. high-grade glioma and brain conditions, respectively. Likewise, the random forest delivered the best performance (root mean square error 1) for the regression of brain conditions. The following factors were discovered to be major predictors of brain image or associated disease: (demographic) age, education, sex; (health-related) alpha desynchronization, Alzheimer’s disease stage, CD4, depression, distress, mild behavioral impairment, RNA sequencing; (neuroimaging) abnormal amyloid-β, amplitude of low-frequency fluctuation, cortical thickness, functional connectivity, fractal dimension measure, gray matter volume, left amygdala activity, left hippocampal volume, plasma neurofilament light, right cerebellum, regional homogeneity, right middle occipital gyrus, surface area, sub-cortical volume. Conclusion: Predictive and explainable artificial intelligence provide an effective, non-invasive decision support system for neuroimaging applications.

Dissecting neural correlates of theory of mind and executive functions in behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia (bvFTD) is characterized by profound and early deficits in social cognition (SC) and executive functions (EF). To date it remains unclear whether deficits of the respective cognitive domains are based on the degeneration of distinct brain regions. In 103 patients with a diagnosis of bvFTD (possible/probable/definite: N = 40/58/5) from the frontotemporal lobar degeneration (FTLD) consortium Germany cohort (age 62.5±9.4 years, gender 38 female/65 male) we applied multimodal structural imaging, i.e. voxel-based morphometry, cortical thickness (CTH) and networks of structural covariance via source based morphometry. We cross-sectionally investigated associations with performance in a modified Reading the Mind in the Eyes Test (RMET; reflective of theory of mind - ToM) and five different tests reflective of EF (i.e. Hamasch-Five-Point Test, semantic and phonemic Fluency, Trail Making Test, Stroop interference). Finally, we investigated the conjunction of RMET correlates with functional networks commonly associated with SC respectively ToM and EF as extracted meta-analytically within the Neurosynth database. RMET performance was mainly associated with gray matter volume (GMV) and CTH within temporal and insular cortical regions and less within the prefrontal cortex (PFC), whereas EF performance was mainly associated with prefrontal regions (GMV and CTH). Overlap of RMET and EF associations was primarily located within the insula, adjacent subcortical structures (i.e. putamen) and the dorsolateral PFC (dlPFC). These patterns were more pronounced after adjustment for the respective other cognitive domain. Corroborative results were obtained in analyses of structural covariance networks. Overlap of RMET with meta-analytically extracted functional networks commonly associated with SC, ToM and EF was again primarily located within the temporal and insular region and the dlPFC. In addition, on a meta-analytical level, strong associations were found for temporal cortical RMET correlates with SC and ToM in particular. These data indicate a temporo-frontal dissociation of bvFTD related disturbances of ToM and EF, with atrophy of the anterior temporal lobe being critically involved in ToM deficits. The consistent overlap within the insular cortex may be attributable to the multimodal and integrative role of this region in socioemotional and cognitive processing.

Increased cerebellar vermis volume following repetitive transcranial magnetic stimulation in drug-resistant epilepsy: a voxel-based morphometry study

IntroductionVoxel-based morphometry (VBM) was applied to explore structural changes induced by repetitive transcranial magnetic stimulation (rTMS) and the relationship with clinical outcomes. Moreover, the relationship between each segmented regional gray matter (GM) volume was investigated to identify circuits involved in the rTMS treatment process in patients with drug-resistant epilepsy (DRE).MethodsNineteen patients with DRE were finally included in the analysis. A session of rTMS was applied for 5 consecutive days. Participants received either 1,000 or 3,000 pulses, at a frequency of 0.5 Hz and the intensity was set at 90% of the individual’s resting motor threshold. VBM analysis was performed to explore regional GM volume changes 2 months after rTMS application. The regional volume change was correlated with seizure reduction rate. Relationships between changes in GM volume in each anatomically parcellated region were analyzed using a fully-automated segmentation pipeline.ResultsCompared to the baseline, seizure frequency was reduced, and quality of life was improved after rTMS treatment. Regional volume was increased in the cerebellar vermis 2 months after rTMS application. The increased cerebellar vermis volume correlated with the reduced seizure frequency. Regional volume changes in the cerebellar vermis were correlated with changes in the subcortical and cortical GM regions including the thalamus, caudate, and frontal cortex.DiscussionThese results indicate that rTMS treatment effectively reduced seizure frequency in patients with DRE. Increased volume in the cerebellar vermis and activations of the cerebello-thalamo-cortical circuit may be a crucial mechanism underlying the effectiveness of rTMS application in patients with DRE.

The mediation role of gray matter volume in the relationship between childhood maltreatment and psychological resilience in adolescents with first-episode major depressive disorder

Previous studies have revealed morphologic alterations in patients with major depressive disorder (MDD) with experiences of childhood trauma. However, the underlying neural mechanisms remain largely unknown. This study aims to explore the brain structural changes and their possible mediation role in the relationship between childhood maltreatment and psychological resilience in drug-naïve adolescents with first-episode MDD. A total of 57 adolescents with first-episode MDD and 36 healthy controls (HCs) completed the T1-weighted magnetic resonance imaging scan. The adverse childhood experiences and current psychological resilience were assessed using the Childhood Trauma Questionnaire-Short Form and the Connor Davidson Resilience Scale, respectively. The voxel-based morphometry approach was applied to examine changes in the gray matter volume (GMV). Compared with the HCs, adolescents with MDD had significantly reduced GMV volumes in the left fusiform gyrus, right orbitofrontal gyrus, right superior temporal gyrus, right calcarine cortex, right middle frontal gyrus, left angular gyrus, right precuneus, right posterior cingulate gyrus, and right posterior central gyrus, as well as significantly increased GMV volumes in the left lenticular putamen and right lenticular pallidum. The GMV of the right calcarine cortex was found to be negatively correlated with the severity of emotional abuse and positively correlated with the level of psychological resilience. Moreover, the GMV of the right calcarine cortex might partially mediate the relationship between childhood maltreatment and psychological resilience. The present study provided further evidence for structural impairments in adolescents with MDD. Our findings also confirmed the important role of depression-related GMV changes in childhood growth experiences and psychological resilience characteristics during adolescent brain maturation.

Pediatric cognitive reserve moderates the effect of brain structure in attention-deficit/hyperactivity disorder: Evidence for an optimized residual approach.

To validate a residual-based cognitive reserve (CR) index optimized for a pediatric sample with attention-deficit/hyperactivity disorder (ADHD). Participants were N = 115 children aged 9.5-13 years at baseline (Mage = 10.48 years, SDage = 0.61), and n = 43 (37.4%) met criteria for ADHD. Elastic-net regularized linear regression was used to generate baseline and longitudinal CR indices by maximally residualizing variance in fluid intelligence for demographics and brain structure. Academic and diagnostic outcomes were regressed onto CR indices, and interactions with brain integrity were assessed. Baseline CR predicted baseline math computation (estimate = 0.10, SE = 0.02, p < .001), while change in CR predicted change in word reading ability (estimate = 0.08, SE = 0.02, p < .001). Further, when grey matter volume tended to be lower, higher CR was associated with higher word reading score (estimate = -0.05, SE = 0.02, p = .019) and lower ADHD symptom severity (estimate = 0.04, SE = 0.02, p = .047) compared to lower CR, at baseline. Similarly, when longitudinal change in white matter hypointensity volume tended to be greater, higher change in CR resulted in more favorable word reading trajectory (estimate = 0.03, SE = 0.02, p = .048). A data-driven residual approach to operationalizing pediatric CR shows better evidence of construct validity over previous methods, with our index showing a novel ability to moderate the deleterious effects of lower grey matter on outcomes in ADHD. This approach may benefit future research aiming to study the early development of CR. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gray Matter Volume Correlates of Co-Occurring Depression in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) involves neurodevelopmental syndromes with significant deficits in communication, motor behaviors, emotional and social comprehension. Often, individuals with ASD exhibit co-occurring depression characterized by a change in mood and diminished interest in previously enjoyable activities. Due to communicative challenges and a lack of appropriate assessments in this cohort, co-occurring depression can often go undiagnosed during routine clinical examinations and, thus, its management neglected. The literature on co-occurring depression in adults with ASD is limited. Therefore, understanding the neural basis of the co-occurring psychopathology of depression in ASD is crucial for identifying brain-based markers for its timely and effective management.Using structural MRI and phenotypic data from the Autism Brain Imaging Data Exchange (ABIDE II) repository, we examined the pattern of relationship regional grey matter volume (rGMV) has with co-occurring depression and autism severity within regions of a priori interest in adults with ASD (n = 44; age = 17-28 years). Further, we performed an exploratory analysis of the rGMV differences between ASD and matched typically developed (TD, n = 39; age = 18-31 years) samples. The severity of co-occurring depression correlated negatively with the rGMV of the right thalamus. Additionally, a significant interaction was evident between the severity of co-occurring depression and core ASD symptoms towards explaining the rGMV in the left cerebellum crus II. The results further the understanding of the neurobiological underpinnings of co-occurring depression in adults with ASD towards exploring neuroimaging-based biomarkers in the same cohort.

Preventive treatment effects on brain structures and functions in patients with chronic migraine: A multimodel magnetic resonance imaging study.

Patients with chronic migraine (CM) often exhibit structural and functional alterations in pain-matrix regions, but it remains unclear how preventive treatment affects these changes. Therefore, this study aimed to investigate the structural and functional changes in pain-matrix regions in CM patients after 6-month treatment. A total of 24 patients with CM and 15 healthy controls were recruited for this study. Patients were divided into responder group (N = 9) and non-responder group (N = 15). After completing the Migraine Disability Assessment (MIDAS) questionnaire, all patients underwent whole-brain high-resolution T1-weighted images, diffusion-weighted imaging, and resting-state functional magnetic resonance imaging at baseline and 6-month follow-up. Whole brain gray matter volume and white matter diffusion indices were analyzed using voxel-based analysis. Structural and functional connectivity analyses were performed to understand brain changes in patients after 6-month preventive treatment. The responder group exhibited significantly higher MIDAS scores than the non-responder group at baseline, but no significant difference between the two groups at follow-up. No significant interval change was noted in gray matter volume, white matter diffusion indices, and structural connectivity in CM patients after 6-month treatment. Nonetheless, the functional connectivity was significantly increased between occipital, temporal lobes and cerebellum, and was significantly decreased between parietal and temporal lobes after 6-month preventive treatment. We concluded that resting-state functional connectivity was suitable for investigating the preventive treatment effect on CM patients.

Pain resilience dimensions and regional gray matter volume as risk factors for poor outcomes of chronic pain: a prospective cohort study.

Pain resilience and regional gray matter volume (rGMV) are established correlates of adaptation to chronic pain within cross-sectional studies. Extending such work, this prospective cohort study tested the status of baseline pain resilience dimension scores and rGMV as risk factors for subsequent exacerbations in chronic pain disability and intensity. 142 adults with chronic musculoskeletal pain completed an initial assessment comprising a structural magnetic resonance imaging scan and self-report measures of cognitive/affective positivity and behavioral perseverance pain resilience dimensions, disability, pain intensity, and demographics. Disability and pain intensity were outcomes re-assessed at a 6-month follow-up. The impact of pain resilience dimension scores and identified rGMV sites on follow-up outcomes was examined after controlling for other baseline correlates of outcomes. Mediating effects of identified rGMV sites on pain resilience dimension-follow-up outcome relations were also evaluated. Aside from the significant multivariate effect of lower behavioral perseverance and cognitive/affective positivity scores, augmented left precuneus, temporal pole, superior temporal gyrus (STG), and precentral gyrus rGMV combined to predict higher follow-up disability levels, independent of covariates. Higher left fusiform gyrus rGMV levels predicted follow-up exacerbations in pain intensity, but pain resilience dimension scores did not. Finally, left precuneus and left temporal pole STG rGMV partially mediated cognitive/affective positivity-follow-up disability relations. Findings underscore deficits in pain resilience and increased rGMV as potential risk factors for poorer subsequent outcomes of chronic musculoskeletal pain and provide foundations for further prospective extensions as well as targeted intervention research.

Gene-Specific Effects on Brain Volume and Cognition of TMEM106B in Frontotemporal Lobar Degeneration.

TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN pathogenic variant carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study was to evaluate and compare the effect of TMEM106B on gray matter volume and cognition in each of the common genetic FTD groups and in patients with sporadic FTD. Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic variant in C9orf72, GRN, MAPT, VCP, TBK1, TARDBP, symptomatic nonpathogenic variant carriers, and noncarrier family controls. All participants were genotyped for the TMEM106B rs1990622 SNP. Cross-sectionally, linear mixed-effects models were fitted to assess an association between TMEM106B and genetic group interaction with each outcome measure (gray matter volume and UDS3-EF for cognition), adjusting for education, age, sex, and CDR+NACC-FTLD sum of boxes. Subsequently, associations between TMEM106B and each outcome measure were investigated within the genetic group. For longitudinal modeling, linear mixed-effects models with time by TMEM106B predictor interactions were fitted. The minor allele of TMEM106B rs1990622, linked to a decreased risk of FTD, associated with greater gray matter volume in GRN pathogenic variant carriers under the recessive dosage model (N = 82, beta = 3.25, 95% CI [0.37-6.19], p = 0.034). This was most pronounced in the thalamus in the left hemisphere (beta = 0.03, 95% CI [0.01-0.06], p = 0.006), with a retained association when considering presymptomatic GRN pathogenic variant carriers only (N = 42, beta = 0.03, 95% CI [0.01-0.05], p = 0.003). The minor allele of TMEM106B rs1990622 also associated with greater cognitive scores among all C9orf72 pathogenic variant carriers (N = 229, beta = 0.36, 95% CI [0.05-0.066], p = 0.021) and in presymptomatic C9orf72 pathogenic variant carriers (N = 106, beta = 0.33, 95% CI [0.03-0.63], p = 0.036), under the recessive dosage model. We identified associations of TMEM106B with gray matter volume and cognition in the presence of GRN and C9orf72 pathogenic variants. The association of TMEM106B with outcomes of interest in presymptomatic GRN and C9orf72 pathogenic variant carriers could additionally reflect TMEM106B's effect on divergent pathophysiologic changes before the appearance of clinical symptoms.

The spine-brain axis: is spinal anatomy associated with brain volume?

First small sample studies indicate that disturbances of spinal morphology may impair craniospinal flow of cerebrospinal fluid and result in neurodegeneration. The aim of this study was to evaluate the association of cervical spinal canal width and scoliosis with grey matter, white matter, ventricular and white matter hyperintensity volumes of the brain in a large study sample. Four hundred participants underwent whole-body 3 T magnetic resonance imaging. Grey matter, white matter and ventricular volumes were quantified using a warp-based automated brain volumetric approach. Spinal canal diameters were measured manually at the cervical vertebrae 2/3 level. Scoliosis was evaluated using manual measurements of the Cobb angle. Linear binomial regression analyses of measures of brain volumes and spine anatomy were performed while adjusting for age, sex, hypertension, cholesterol levels, body mass index, smoking and alcohol consumption. Three hundred eighty-three participants were included [57% male; age: 56.3 (±9.2) years]. After adjustment, smaller spinal canal width at the cervical vertebrae 2/3 level was associated with lower grey matter (P = 0.034), lower white matter (P = 0.012) and higher ventricular (P = 0.006, inverse association) volume. Participants with scoliosis had lower grey matter (P = 0.005), lower white matter (P = 0.011) and larger brain ventricular (P = 0.003) volumes than participants without scoliosis. However, these associations were attenuated after adjustment. Spinal canal width at the cervical vertebrae 2/3 level and scoliosis were not associated with white matter hyperintensity volume before and after adjustment (P > 0.864). In our study, cohort smaller spinal canal width at the cervical vertebrae 2/3 level and scoliosis were associated with lower grey and white matter volumes and larger ventricle size. These characteristics of the spine might constitute independent risk factors for neurodegeneration.

Large-scale structural covariance networks changes relate to executive function deficit in betel quid-dependent chewers.

Previous studies demonstrate deficits in executive function for betel quid-dependent (BQD) patients. Large-scale structural covariance network (SCN) based on gray matter (GM) morphometry may be able to explore the neural mechanism of executive dysfunction in BQD individuals. This study aims to identify spatial covariance patterns of GM volume and to investigate their association with executive dysfunction in BQD individuals. Sixty-four BQD individuals and 48 sex- and age-matched healthy controls (HCs) underwent T1-weighted structural MRI examination and executive function assessments, including the Backward Digit Span (BDS) test and Stroop Color and Word (SCW) test. Seventy SCNs based on GM volume covariance patterns were defined using independent component analysis. An SCN-based classifier was constructed to differentiate between BQD and HC individuals. Receiver operating characteristic (ROC) curves were applied to evaluate the performance of the SCN-based classifier. Linear regression analyses were performed to investigate the association between SCN network indices and executive function indices. Six SCNs had higher classifications for differentiating between BQD and HC individuals. The area under the ROC curve of the SCN-based classifier was 0.812 in the training set and 0.771 in the testing set. Furthermore, linear regression analyses demonstrated that the network indices in the thalamus were associated with BDS scores adjusted for age, sex, and education. Large-scale SCNs could provide potential imaging markers for differentiating BQD and HC groups. The loss of network index in the thalamus was associated with working memory, indicating that SCNs could reveal executive dysfunction in BQD individuals.

Exploring the links among brain iron accumulation, cognitive performance, and dietary intake in older adults: A longitudinal MRI study

This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60–86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5–3.0 years later. Dietary intake was evaluated at baseline using a validated questionnaire. Cognitive performance was assessed at TP2 using the uniform data set (Version 3) neuropsychological tests of episodic memory (MEM) and executive function (EF). Voxel-wise, linear mixed-effects models, adjusted for longitudinal gray matter volume alterations, age, and several non-dietary lifestyle factors revealed brain iron accumulation in multiple subcortical and cortical brain regions, which was negatively associated with both MEM and EF performance at T2. However, consumption of specific dietary nutrients at TP1 was associated with reduced brain iron accumulation. Our study provides a map of brain regions showing iron accumulation in older adults over a short 2.5-year follow-up and indicates that certain dietary nutrients may slow brain iron accumulation.

Associations Between High-Density Lipoprotein Cholesterol Efflux and Brain Grey Matter Volume.

Objective: High-density lipoprotein cholesterol efflux function may prevent brain amyloid beta deposition and neurodegeneration. However, the relevance of this finding has not been established in the diverse middle-aged population. Methods: We examined 1826 adults (47% Black adults) who participated in the Dallas Heart Study to determine associations between high-density lipoprotein (HDL) measures and brain structure and function. White matter hyperintensities (WMH) and whole-brain grey matter volume (GMV) were measured using brain MRI, and the Montreal Cognitive Assessment (MoCA) was used to measure neurocognitive function. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages, and HDL particle size measures were assessed using nuclear magnetic resonance (NMR) spectroscopy (LipoScience). Multivariable linear regressions were performed to elucidate associations between HDL-CEC and brain and cognitive phenotypes after adjustment for traditional risk factors such as age, smoking status, time spent in daily physical activity, and education level. Results: Higher HDL-CEC and small HDL particle (HDL-P) concentration were positively associated with higher GMV normalized to total cranial volume (TCV) (GMV/TCV) after adjustment for relevant risk factors (β = 0.078 [95% CI: 0.029, 0.126], p = 0.002, and β = 0.063 [95% CI: 0.014, 0.111], p = 0.012, respectively). Conversely, there were no associations between HDL measures and WMH or MoCA (all p > 0.05). Associations of HDL-CEC and small HDL-P with GMV/TCV were not modified by ApoE-ε4 status or race/ethnicity. Interpretation: Higher HDL cholesterol efflux and higher plasma concentration of small HDL-P were associated with higher GMV/TCV. Additional studies are needed to explore the potential neuroprotective functions of HDL.

Frontoparietal network integrity supports cognitive function in pre-symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion.

Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre-symptomatic stage could inform accurate staging and potential mechanisms. We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations. The gray matter volume, cerebral perfusion, and resting-state functional network maps were co-analyzed using linked independent component analysis (LICA). Multiple regression analysis was used to investigate the relationship of LICA components to genetic status and cognition. Pre-symptomatic mutation carriers showed an age-related decrease in the left frontoparietal network integrity, while non-carriers did not. Executive functions of mutation carriers became dependent on the left frontoparietal network integrity in older age. The frontoparietal network integrity of pre-symptomatic mutation carriers showed a distinctive relationship to age and cognition compared to non-carriers, suggesting a contribution of the network integrity to brain resilience. A multimodal analysis of structure, perfusion, and functional networks. The frontoparietal network integrity decreases with age in pre-symptomatic carriers only. Executive functions of pre-symptomatic carriers dissociated from non-carriers.

Sex Differences in Human Brain Structure at Birth

BackgroundSex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.MethodsHere, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0–28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.ResultsOn average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).ConclusionsOur findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.