White Matter Fractional Anisotropy Research Articles

Identification and validation of supervariants reveal novel loci associated with human white matter microstructure.

As an essential part of the central nervous system, white matter coordinates communications between different brain regions and is related to a wide range of neurodegenerative and neuropsychiatric disorders. Previous genome-wide association studies (GWASs) have uncovered loci associated with white matter microstructure. However, GWASs suffer from limited reproducibility and difficulties in detecting multi-single-nucleotide polymorphism (multi-SNP) and epistatic effects. In this study, we adopt the concept of supervariants, a combination of alleles in multiple loci, to account for potential multi-SNP effects. We perform supervariant identification and validation to identify loci associated with 22 white matter fractional anisotropy phenotypes derived from diffusion tensor imaging. To increase reproducibility, we use United Kingdom (UK) Biobank White British (n = 30,842) data for discovery and internal validation, and UK Biobank White but non-British (n = 1927) data, Europeans from the Adolescent Brain Cognitive Development study (n = 4399) data, and Europeans from the Human Connectome Project (n = 319) data for external validation. We identify 23 novel loci on the discovery set that have not been reported in the previous GWASs on white matter microstructure. Among them, three supervariants on genomic regions 5q35.1, 8p21.2, and 19q13.32 have P-values lower than 0.05 in the meta-analysis of the three independent validation data sets. These supervariants contain genetic variants located in genes that have been related to brain structures, cognitive functions, and neuropsychiatric diseases. Our findings provide a better understanding of the genetic architecture underlying white matter microstructure.

ECHDC3 Variant Regulates the Right Hippocampal Microstructural Integrity and Verbal Memory in Type 2 Diabetes Mellitus

ECHDC3 is a risk gene for white matter (WM) hyperintensity and is associated with insulin resistance. This study aimed to investigate whether ECHDC3 variants selectively regulate brain WM microstructures and episodic memory in patients with type 2 diabetes mellitus (T2DM). We enrolled 106 patients with T2DM and 111 healthy controls. A voxel-wise general linear model was employed to explore the interaction effect between ECHDC3 rs11257311 polymorphism and T2DM diagnosis on fractional anisotropy (FA). A linear modulated mediation analysis was conducted to examine the potential of FA value to mediate the influence of T2DM on episodic memory in an ECHDC3-dependent manner. We observed a noteworthy interaction between genotype and diagnosis on FA in the right inferior temporal WM, right anterior limb of the internal capsule, right frontal WM, and the right hippocampus. Modulated mediation analysis revealed a significant ECHDC3 modulation on the T2DM → right hippocampal FA → short-term memory pathway, with only rs11257311 G risk homozygote demonstrating significant mediation effect. Together, our findings provide evidence of ECHDC3 modulating the effect of T2DM on right hippocampal microstructural impairment and short-term memory decline, which might be a neuro-mechanism for T2DM related episodic memory impairment.

Impact of Decreased Visibility of Deep Medullary Veins on White Matter Integrity in Patients with Cerebral Small Vessel Disease.

Based on susceptibility-weighted imaging (SWI) visibility, deep medullary vein (DMV) scores are related to white matter damage (WMD) in patients with cerebral small vessel disease (CSVD). However, whether mechanisms are associated with DMV changes is unclear. We examined extracellular fluid (ECF) roles in white matter associations between DMV scores and white matter integrity (WMI) in patients with CSVD. We examined magnetic resonance imaging (MRI) and clinical data from 140 patients with CSVD. DMV scores (0-18) were assigned on SWI according to DMV anatomic regions and signal continuity/visibility. WMI and ECF volumes were evaluated using free water (FW) and fractional anisotropy (FA) values by diffusion tensor imaging (DTI). DMV scores were independently associated with FA after adjusting for vascular risk factors, age, white matter hyperintensity (WMH) volume, and CSVD burden [β (95% confidence interval (CI)): -0.219 (-0.375, -0.061), p = 0.006]. We also observed a significant indirect effect of DMV scores on FA in white matter (mediated by FW in white matter) after controlling for age, vascular risk factors, WMH volume, and CSVD burden. DMV scores were independently related to WMI and mediated by ECF in the white matter of patients with CSVD.

Gamma‐band transcranial alternating current stimulation in amnestic mild cognitive impairment: A pilot study

AbstractBackgroundAmnestic mild cognitive impairment (aMCI) is a pre‐dementia stage of Alzheimer’s disease (AD) associated with dysfunctional episodic memory and limited treatment options. Recent findings from animal models of AD show that 40 Hz (gamma) stimulation (e.g., through light, sound, magnetic, or electrical stimulation sources) can improve episodic memory and learning, can facilitate neurogenesis, and can also reduce biomarkers associated with AD pathology including beta‐amyloid (Aβ) and tau. Although preliminary studies regarding the efficacy of gamma stimulation in humans has been promising, evidence is limited, neuroplastic changes are unclear, and the feasibility of electrical‐based gamma stimulation is still under investigation. Here, we aimed to characterize feasibility and neuroplastic changes associated with possible improvements in episodic memory following electrical non‐invasive neurostimulation.Method13 individuals with aMCI received eight 60‐minute sessions of 40‐Hz (gamma) transcranial alternating current stimulation (tACS), in a single‐arm design. Primary outcomes assessed side‐effects and drop‐out as indicators of feasibility. Secondary outcomes included episodic memory, plasma‐based Aβ and tau. Exploratory measures included neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and white matter fractional anisotropy. Additionally, neuroplastic changes were characterized by resting state functional connectivity (RSFC) within an episodic memory network and neuronal excitatory/inhibitory (Glx/GABA) balance via magnetic resonance spectroscopy.ResultResults revealed that gamma tACS was feasible (minimal side effects and no drop‐outs due to tACS). Moreover, aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in Aβ, tau, NfL, or GFAP. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS‐induced electric fields and exhibited the greatest changes in RSFC – all within an episodic memory network. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity across numerous tracts.ConclusionThis study highlights the potential of gamma tACS to improve episodic memory in an aMCI population by modulating functional connectivity and excitability within an episodic memory network.

Enlarged Perivascular Spaces in a Diverse Community‐based Sample. The Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundEnlarged perivascular spaces (ePVS) have been associated with small vessel disease of the brain (SVD). Nevertheless, the burden, correlates and significance of ePVS have been studied predominantly in White individuals, so the generalizability of these findings to other racial/ethnic groups remains uncertain. Herein, we present an investigation of ePVS in a large, multi‐ethnic, community‐based cohort.MethodePVS volumes were quantified in 1,026 participants (median age 71 years; 47% men) from the Multi‐Ethnic Study of Atherosclerosis, using a fully‐automated deep learning model with 82% lesion‐wise sensitivity. Based on previously‐described clinical rating systems, ePVS were grouped in four brain regions: basal ganglia, thalamus, frontoparietal region, and temporal region, and were normalized to the respective regional volumes. Cognition was assessed with the Cognitive Abilities Screening Instrument, the Digit Symbol Coding, and the Digit Span test. APOE‐ε4 isoforms were estimated from single nucleotide polymorphisms (rs429358,rs7412). The relationships of normalized regional ePVS volumes with demographic and vascular risk factors, neuroimaging indices, cognition, and APOE genotype were explored using generalized linear models.ResultBasal ganglia was the anatomic region with the largest ePVS burden (median[IQR] = 1.9[1.4] % of total regional volume), followed by the frontoparietal region (0.6[0.5]), temporal region (0.4[0.4]), and thalamus (0.3[0.3]) – Figure 1,Table 1. Basal ganglia ePVS volume was positively associated with age, systolic blood pressure (SBP), use of antihypertensives, white matter hyperintensity volume (WMHV), and microbleeds (MBs), and negatively associated with white matter fractional anisotropy (FA) and Black race (Tables 1,2). Thalamic ePVS volume was positively associated with age, use of antihypertensives, WMHV, and MBs, and negatively associated with FA. Frontoparietal ePVS volume was positively associated with SBP, and negatively associated with age. Temporal region ePVS volume was negatively associated with age, Chinese and Hispanic ethnicity. No significant associations were observed between regional ePVS volumes and cognition or APOE genotype.ConclusionIncreased ePVS burden in the basal ganglia and thalamus was associated with hypertension and imaging biomarkers of vascular brain damage in a multi‐ethnic population of older adults, likely reflecting underlying SVD. Compared to other racial/ethnic groups, White race was associated with higher ePVS burden in the basal ganglia and temporal regions.

Clinical Manifestations.

Education level is a well-recognized co-factor for cognitive performance and a potential confounder in the application of cognitive evaluations in diverse populations. The Montreal Cognitive Assessment (MoCA) is a widely utilized screening tool for Mild Cognitive Impairment (MCI) composed of 6 domains of cognition: Executive Function (EFC), Attention and Concentration (AC), Language (LANG), Visuospatial (VIS), Memory (MEM), and Orientation (ORIEN). Education is currently accounted for globally by adding 1 point to the total MoCA score. This study considers the impact of education level on a domain-specific scoring of the MoCA. We utilized longitudinal subject level data from one site within the MarkVCID Consortium (UCSF) composed of 578 subjects (59.5% female; 82.9% white), mean age 71.5 (+/- 8.7). Mean educational level was 15.3 (+/-4.7) years. Within the cohort, 37 subjects lacked educational level and were omitted (final n = 541). Multivariate linear regression models were used to relate educational level with total and domain specific MoCA score performance at baseline while controlling for the influence of age, sex, and recognized MarkVCID biomarkers that impact cognitive performance including white matter hyperintensity (logWMH), fractional anisotropy (FA), free water (FW), and peak width of skeletonized mean diffusivity (PSMD). An age-, sex-adjusted model replicated a significant association of education level with MoCA total score (p<0.001, b = .336). Among the MoCA domains, EFC was most affected by education level (p<.001, b = .412), followed by AC (p<.001, b = .352). Other MoCA domains were not significantly associated with educational level. Several MoCA domains, namely MEM and ORIEN, showed an association with MarkVCID biomarkers including WMH and FW (p-values <.001). In regression models controlled for MarkVCID imaging biomarkers, educational level remained significantly associated with total and domain-specific MoCA performance. Education does not equally contribute to all cognitive domains assessed by the MoCA, mostly affecting EFC and AC. These findings suggest that considering education level in a domain-specific manner could provide a more accurate interpretation of the cognitive impairment.

Role of Social, Clinical, and Contextual Factors in Explaining MRI Markers of White Matter Injury and Change in Objectively‐Assessed Cognition by Race/Ethnicity: The Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundRacial and ethnic disparities in Alzheimer’s disease and related dementias (ADRD) are well documented. The mechanisms through which race and ethnicity as markers of systemic racism are associated with brain health are lacking.MethodWe used data from the Multi‐Ethnic Study of Atherosclerosis (MESA) and a causal mediation framework to determine whether the association between race/ethnicity (measured in Exam 1, 2000‐2002) and brain health is mediated through pathways represented by social (education level, health insurance (yes/no)), clinical (hypertension, diabetes, and depression symptoms), and contextual factors (neighborhood socioeconomic status) measured in Exam 1. Brain health was measured by 3T magnetic resonance imaging (MRI, N = 966) and change in cognitive scores (N = 2002). Participants completed the Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive tests in Exams 5 (2010‐2012) and 6 (2016‐2018). Participants underwent MRI in 2018‐2019 to assess white matter (WM) injury assessed by WM hyperintensity volume (WMHV) and fractional anisotropy (FA). All models were adjusted for age, gender, education, marital status, income, and for WMHV models, total intracranial volume.ResultMean (SD) age at baseline was 58 (9) years, 29% participants self‐reported Black, 17% Hispanic, 11% Chinese and 43% White. Black and Hispanic participants experienced a larger decrease in CASI (‐3.3 points (95%CI: ‐4.1, ‐2.5); ‐4.7 (‐5.7, ‐3.7) respectively), DSC (‐2.2 (‐3.6,‐0.8); ‐5.3 (‐7.0,‐3.6)), and DS scores (‐0.4 (‐0.7,‐0.2); ‐1.1 (‐1.4,‐0.8)) from Exam5 to 6 than White participants, after accounting for covariates and baseline cognitive score. Black participants had greater WMHV (21% (1%, 50%)), and lower FA (‐.006 (‐0.01,‐0.002)) than White participants. We observed that the association between race/ethnicity as markers of racism and CASI change was mediated by education (proportion mediated 13% (1%, 21%)), and that the association with DSC change was mediated by health insurance (proportion mediated 9% (4%, 24%)) but not by any other social, clinical or contextual factor. The association between race/ethnicity and WM injury markers and change in DS was not mediated by social, clinical nor contextual factors.ConclusionEducation and health insurance appear as factors that may partially explain the association between race/ethnicity and cognitive decline.

Heart rate fragmentation and brain MRI markers of small vessel disease in MESA.

Heart rate (HR) fragmentation indices quantify breakdown of HR regulation and are associated with atrial fibrillation and cognitive impairment. Their association with brain magnetic resonance imaging (MRI) markers of small vessel disease is unexplored. In 606 stroke-free participants of the Multi-Ethnic Study of Atherosclerosis (mean age 67), HR fragmentation indices including percentage of inflection points (PIP) were derived from sleep study recordings. We examined PIP in relation to white matter hyperintensity (WMH) volume, total white matter fractional anisotropy (FA), and microbleeds from 3-Tesla brain MRI completed 7 years later. In adjusted analyses, higher PIP was associated with greater WMH volume (14% per standard deviation [SD], 95% confidence interval [CI]: 2, 27%, P=0.02) and lower WM FA (-0.09 SD per SD, 95% CI: -0.16, -0.01, P=0.03). HR fragmentation was associated with small vessel disease. HR fragmentation can be measured automatically from ambulatory electrocardiogram devices and may be useful as a biomarker of vascular brain injury.

Characterizing microstructural development in the fetal brain using diffusion MRI from 23 to 36weeks of gestation.

We utilized motion-corrected diffusion tensor imaging (DTI) to evaluate microstructural changes in healthy fetal brains during the late second and third trimesters. Data were derived from fetal magnetic resonance imaging scans conducted as part of a prospective study spanning from 2013 March to 2019 May. The study included 44 fetuses between the gestational ages (GAs) of 23 and 36weeks. We reconstructed fetal brain DTI using a motion-tracked slice-to-volume registration framework. Images were segmented into 14 regions of interest (ROIs) through label propagation using a fetal DTI atlas, with expert refinement. Statistical analysis involved assessing changes in fractional anisotropy (FA) and mean diffusivity (MD) throughout gestation using mixed-effects models, and identifying points of change in trajectory for ROIs with nonlinear trends. Results showed significant GA-related changes in FA and MD in all ROIs except in the thalamus' FA and corpus callosum's MD. Hemispheric asymmetries were found in the FA of the periventricular white matter (pvWM), intermediate zone, and subplate and in the MD of the ganglionic eminence and pvWM. This study provides valuable insight into the normal patterns of development of MD and FA in the fetal brain. These changes are closely linked with cytoarchitectonic changes and display indications of early functional specialization.

Deep learning-based grading of white matter hyperintensities enables identification of potential markers in multi-sequence MRI data

BackgroundWhite matter hyperintensities (WMHs) are widely-seen in the aging population, which are associated with cerebrovascular risk factors and age-related cognitive decline. At present, structural atrophy and functional alterations coexisted with WMHs lacks comprehensive investigation. This study developed a WMHs risk prediction model to evaluate WHMs according to Fazekas scales, and to locate potential regions with high risks across the entire brain. MethodsWe developed a WMHs risk prediction model, which consisted of the following steps: T2 fluid attenuated inversion recovery (T2-FLAIR) image of each participant was firstly segmented into 1000 tiles with the size of 32 × 32 × 1, features from the tiles were extracted using the ResNet18-based feature extractor, and then a 1D convolutional neural network (CNN) was used to score all tiles based on the extracted features. Finally, a multi-layer perceptron (MLP) was constructed to predict the Fazekas scales based on the tile scores. The proposed model was trained using T2-FLAIR images, we selected tiles with abnormal scores in the test set after prediction, and evaluated their corresponding gray matter (GM) volume, white matter (WM) volume, fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF) via longitudinal and multi-sequence Magnetic Resonance Imaging (MRI) data analysis. ResultsThe proposed WMHs risk prediction model could accurately predict the Fazekas ratings based on the tile scores from T2-FLAIR MRI images with accuracy of 0.656, 0.621 in training data set and test set, respectively. The longitudinal MRI validation revealed that most of the high-risk tiles predicted by the WMHs risk prediction model in the baseline images had WMHs in the corresponding positions in the longitudinal images. The validation on multi-sequence MRI demonstrated that WMHs were associated with GM and WM atrophies, WM micro-structural and perfusion alterations in high-risk tiles, and multi-modal MRI measures of most high-risk tiles showed significant associations with Mini Mental State Examination (MMSE) score. ConclusionOur proposed WMHs risk prediction model can not only accurately evaluate WMH severities according to Fazekas scales, but can also uncover potential markers of WMHs across modalities. The WMHs risk prediction model has the potential to be used for the early detection of WMH-related alterations in the entire brain and WMH-induced cognitive decline.

Age-related, multivariate associations between white matter microstructure and behavioral performance in three executive function domains

The executive function (EF) domains of working memory (WM), response inhibition (RI), and set shifting (SS) show maturational gains and are linked to neuroimaging-measured brain changes. This study explored ways in which maturation-linked differences in EF abilities are systematically associated with white matter microstructural differences from adolescence into young adulthood. Diffusion tensor imaging (DTI) and nine neurocognitive tests were collected from 120 healthy subjects ages 12–24. Analyses across the white matter skeleton were performed, focusing on fractional anisotropy (FA). Data were ‘fused’ using a multivariate technique (CCA+jICA), producing four independent components (ICs) depicting white matter FA values that covaried with test performance. Correlations between age and IC loading coefficients identified three EF-DTI profiles that may change developmentally. In one, SS performance was linked to greater reliance on the FA of ventral brain tracts, and less on dorsal tracts with age. In another, white matter microstructure was related to a pattern of strong WM and weak SS that became more pronounced with age. A final IC revealed that younger individuals with low RI and high WM/SS skills typically matured out of this cognitive imbalance, underscored by white matter changes with age. These novel multivariate results begin to emphasize the complexity of brain structure-cognition relationships in adolescents and young adults.

White matter microstructural integrity is associated with retinal vascular caliber in adolescents with bipolar disorder

ObjectiveReduced white matter integrity is observed in bipolar disorder (BD), and is associated with cardiovascular risk in adults. This topic is underexplored in youth, and in BD, where novel microvascular measures may help to inform understanding of the vascular-brain connection. We therefore examined the association of retinal vascular caliber with white matter integrity in a cross-sectional sample of adolescents with and without BD. MethodsEighty-four adolescents (n = 42 BD, n = 42 controls) completed retinal imaging, yielding arteriolar and venular caliber. Diffusion tensor imaging measured white matter fractional anisotropy (FA). Multiple linear regression tested associations between retinal vascular caliber and FA in regions-of-interest; corpus callosum, anterior thalamic radiation, uncinate fasciculus, and superior longitudinal fasciculus. Complementary voxel-wise analyses were performed. ResultsArteriolar caliber was elevated in adolescents with BD relative to controls (F(1,79) = 6.15, p = 0.02, η2p = 0.07). In the overall sample, higher venular caliber was significantly associated with lower corpus callosum FA (β = −0.24, puncorrected = 0.04). In voxel-wise analyses, higher arteriolar caliber was significantly associated with lower corpus callosum and forceps minor FA in the overall sample (β = −0.46, p = 0.03). A significant diagnosis-by-venular caliber interaction on FA was noted in 5 clusters including the right retrolenticular internal capsule (β = 0.72, p = 0.03), corticospinal tract (β = 0.72, p = 0.04), and anterior corona radiata (β = 0.63, p = 0.04). In each instance, venular caliber was more positively associated with FA in BD vs. controls. ConclusionRetinal microvascular measures are associated with white matter integrity in BD, particularly in the corpus callosum. This study was proof-of-concept, designed to guide future studies focused on the vascular-brain interface in BD.

Psychiatric disorders and brain white matter exhibit genetic overlap implicating developmental and neural cell biology.

Improved understanding of the shared genetic architecture between psychiatric disorders and brain white matter may provide mechanistic insights for observed phenotypic associations. Our objective is to characterize the shared genetic architecture of bipolar disorder (BD), major depression (MD), and schizophrenia (SZ) with white matter fractional anisotropy (FA) and identify shared genetic loci to uncover biological underpinnings. We used genome-wide association study (GWAS) summary statistics for BD (n = 413,466), MD (n = 420,359), SZ (n = 320,404), and white matter FA (n = 33,292) to uncover the genetic architecture (i.e., polygenicity and discoverability) of each phenotype and their genetic overlap (i.e., genetic correlations, overlapping trait-influencing variants, and shared loci). This revealed that BD, MD, and SZ are at least 7-times more polygenic and less genetically discoverable than average FA. Even in the presence of weak genetic correlations (range = -0.05 to -0.09), average FA shared an estimated 42.5%, 43.0%, and 90.7% of trait-influencing variants as well as 12, 4, and 28 shared loci with BD, MD, and SZ, respectively. Shared variants were mapped to genes and tested for enrichment among gene-sets which implicated neurodevelopmental expression, neural cell types, myelin, and cell adhesion molecules. For BD and SZ, case vs control tract-level differences in FA associated with genetic correlations between those same tracts and the respective disorder (rBD = 0.83, p = 4.99e-7 and rSZ = 0.65, p = 5.79e-4). Genetic overlap at the tract-level was consistent with average FA results. Overall, these findings suggest a genetic basis for the involvement of brain white matter aberrations in the pathophysiology of psychiatric disorders.

Association of Olfaction and Microstructural Integrity of Brain Tissue in Community-Dwelling Adults: Atherosclerosis Risk in Communities Neurocognitive Study.

Research on olfaction and brain neuropathology may help understand brain regions associated with normal olfaction and dementia pathophysiology. To identify early regional brain structures affected in poor olfaction, we examined cross-sectional associations of microstructural integrity of the brain with olfaction in the Atherosclerosis Risk in Communities Neurocognitive Study. Participants were selected from a prospective cohort study of community-dwelling adults; selection criteria included the following: evidence of cognitive impairment, participation in a previous MRI study, and a random sample of cognitively normal participants. Microstructural integrity was measured by 2 diffusion tensor imaging (DTI) measures, fractional anisotropy (FA) and mean diffusivity (MD), and olfaction by a 12-item odor identification test at the same visit. Higher FA and MD values indicate better and worse microstructural integrity, respectively, and higher odor identification scores indicate better olfaction. We used brain region-specific linear regression models to examine associations between DTI measures and olfaction, adjusting for potential confounders. Among 1,418 participants (mean age 76 ± 5 years, 41% male, 21% Black race, 59% with normal cognition), the mean olfaction score was 9 ± 2.3. Relevant to olfaction, higher MD in the medial temporal lobe (MTL) regions, namely the hippocampus (β -0.79 [95% CI -0.94 to -0.65] units lower olfaction score per 1 SD higher MD), amygdala, entorhinal area, and some white matter (WM) tracts connecting to these regions, was associated with olfaction. We also observed associations with MD and WM FA in multiple atlas regions that were not previously implicated in olfaction. The associations between MD and olfaction were particularly stronger in the MTL regions among individuals with mild cognitive impairment (MCI) compared with those with normal cognition (e.g., βhippocampus -0.75 [95% CI -1.02 to -0.49] and -0.44 [95% CI -0.63 to -0.26] for MCI and normal cognition, respectively, p interaction = 0.004). Neuronal microstructural integrity in multiple brain regions, particularly the MTL (the regions known to be affected in early Alzheimer disease), is associated with odor identification ability. Differential associations in the MTL regions among cognitively normal individuals compared with those with MCI may reflect the earlier vs later effects of the dementia pathogenesis. It is likely that some of the associated regions may not have any functional relevance to olfaction.

Evaluation of the white matter integrity in morbidly obese patients before and after bariatric surgery; a diffusion tensor imaging study.

To investigate the difference in FA (Fractional anisotropy), ADC (Apparent diffusion coefficient), RD (Radial diffusivity) and AD (axial diffusivity) values of white matter (WM) tracts in morbidly obese subjects before and after bariatric surgery (BS). A group of thirty-nine morbidly obese subjects are evaluated before and 4-6 months after BS. ADC, FA, RD and AD values of 17 distinct neuroanatomic localizations are measured and DTI parameters are analyzed. Following the BS, the patients' mean BMI decreased from 47.665.21 to 31.723.97. A significant difference is displayed between the pre-surgery and post-surgery FA values of SLF, SFOF, ALIC, fornix, ILF, CST, MCP (p = 0.010, p < 0.001, p = 0.048, p = 0.014, p = 0.012, p = 0.012, p = 0.040 respectively). Following BS, decrease in FA values in the mentioned areas are detected. ADC values obtained from MCP are significantly lower in the post-BS period compared to pre-BS period (p = 0.018). There was a statistically significant difference between the pre-surgery and post-surgery AD values of SLF, SFOF, ILF, ALIC, EC, CST, and MCP (p = 0.001, p = 0.022, p = 0.001, p = 0.011, p = 0.001, p = 0.000, p = 0.000, respectively). Following the BS, AD values of the SLF, SFOF, ILF, ALIC, EC, CST, and MCP are decreased. RD values measured from GCC are significantly lower in the post-BS period compared to pre-BS period (p = 0.008). Our study supported the hypothesis of the BS-induced reversibility of the low-grade inflammation in WM tracts in the morbidly obese group following BS. Our DTI results may represent the subacute period findings of the reversal of low-grade inflammation after BS.

Sex-related differences in upper limb motor function in healthy subjects and multiple sclerosis patients: a multiparametric MRI study.

We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS.

Structure of brain grey and white matter in infants with spastic cerebral palsy and periventricular white matter injury.

To investigate the possible covariation of grey matter volume (GMV) and white matter fractional anisotropy in infants with spastic cerebral palsy (CP) and periventricular white matter injury. Thirty-nine infants with spastic CP and 25 typically developing controls underwent structural magnetic resonance imaging and diffusion tensor imaging. Multimodal canonical correlation analysis with joint independent component analysis were used to capture differences in GMV and fractional anisotropy between groups. Correlation analysis was performed between imaging findings and clinical features. Infants with spastic CP showed one joint group-discriminating component (i.e. GMV-fractional anisotropy) associated with regions in the cortico-basal ganglia-thalamo-cortical loop and in the corpus callosum compared to typically developing controls and one modality-specific group-discriminating component (i.e. GMV). Significant negative correlations were found between loadings in certain regions and the motor function score in spastic CP. In infants with spastic CP, covarying GMV-fractional anisotropy and altered GMV in specific regions were implicated in motor dysfunction, which confirmed that simultaneous GMV and fractional anisotropy changes underly motor deficits, but might also extend to sensory, cognitive, or visual dysfunction. These findings also suggest that multimodal fusion analysis allows for a more comprehensive understanding of the relevance between grey and white matter structures and its crucial role in the neuropathological mechanisms of spastic CP.

Measures of MRI Brain Biomarkers in Middle Age According to Average Modified Mediterranean Diet Scores Throughout Young and Middle Adulthood.

The Mediterranean diet (MedDiet) has been linked with better cognitive function and brain integrity. To examine the association of modified Mediterranean diet (mMedDiet) scores from early through middle adulthood in relation to volumetric and microstructural midlife MRI brain measures. Assess the association of mMedDiet and brain measures with four cognitive domains. If variables are correlated, determine if brain measures mediate the relationship between mMedDiet and cognition. 618 participants (mean age 25.4±3.5 at year 0) of the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Cumulative average mMedDiet scores were calculated by averaging scores from years 0, 7, and 20. MRI scans were obtained at years 25 and 30. General linear models were used to examine the association between mMedDiet and brain measures. Higher cumulative average mMedDiet scores were associated with better microstructural white matter (WM) integrity measured by fractional anisotropy (FA) at years 25 and 30 (all ptrend <0.05). Higher mMedDiet scores at year 7 were associated with higher WM FA at year 25 (β= 0.003, ptrend = 0.03). Higher mMedDiet scores at year 20 associated with higher WM FA at years 25 (β= 0.0005, ptrend = 0.002) and 30 (β= 0.0003, ptrend = 0.02). mMedDiet scores were not associated with brain volumes. Higher mMedDiet scores and WM FA were both correlated with better executive function, processing speed, and global cognition (all ptrend <0.05). WM FA did not mediate the association between mMedDiet scores and cognition. mMedDiet scores may be associated with microstructural WM integrity at midlife.

Magnetic resonance advanced imaging analysis in adolescents: cortical thickness study to identify attenuated psychosis syndrome.

Psychosis is a symptom common to several mental illnesses and a defining feature of schizophrenia spectrum disorders, whose onset typically occurs in adolescence. Neuroradiological studies have reported evidence of brain structural abnormalities in patients with overt psychosis. However, early identification of brain structural changes in young subjects at risk for developing psychosis (such as those with Attenuated Psychosis Syndrome -APS) is currently lacking. Brain 3D T1-weighted and 64 directions diffusion-weighted images were acquired on 55 help-seeking adolescents (12-17years old) with psychiatric disorders who referred to our Institute. Patients were divided into three groups: non-APS (n = 20), APS (n = 20), and Early-Onset Psychosis (n = 15). Cortical thickness was calculated from T1w images, and Tract-Based Spatial Statistics analysis was performed to study the distribution of white matter fractional anisotropy and all diffusivity metrics. A thorough neuropsychological test battery was adopted to investigate cognitive performance in several domains. In patients with Attenuated Psychotic Syndrome, the left superior frontal gyrus was significantly thinner compared to patients with non-APS (p = 0.048), and their right medial orbitofrontal cortex thickness was associated with lower working memory scores (p = 0.0025, r = -0.668 for the working memory index and p = 0.001, r = -0.738 for the digit span). Early-Onset Psychosis patients showed thinner left pars triangularis compared to non-APS individuals (p = 0.024), and their left pars orbitalis was associated with impaired performance at the symbol search test (p = 0.005, r = -0.726). No differences in diffusivity along main tracts were found between sub-groups (p > 0.05). This study showed specific associations between structural imaging features and cognitive performance in patients with APS. Characterizing this disorder using neuroimaging could reveal useful information that may aid in the development and evaluation of preventive strategies in these individuals.

Migraine and white matter lesions: a mendelian randomization study

Previous studies have found that migraine patients are associated with white matter lesions (WMLs), but the causal relationship between the two remains unclear. We intend to explore the bidirectional causal relationship between migraine and WMLs using a two-sample mendelian randomization (MR) method. We employed summary-level data from a recent large-scale genome-wide association study (GWAS) that characterized three white matter (WM) phenotypes: white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467), as well as migraine (N = 589,356). The inverse variance-weighted (IVW) method was used as the main approach for analyzing causality. Weighted median analysis, simple median analysis, and MR-Egger regression served as complementary methods. The bidirectional MR study affords no support for causality between WMLs and migraine. In all MR methods, there was no obvious causal evidence between them. In our bidirectional MR study, we didn't reach this conclusion that WMLs can cause migraine, migraine wouldn’t increase the risk of WMLs, either.