Fractional Anisotropy In Tracts Research Articles

Abstract 66: Diffusion Imaging Demonstrates White Matter Alterations In Children With Moyamoya In Watershed Tracts

Introduction: Moyamoya is a progressive cerebrovascular disease leading to stenosis of arteries located in the circle of Willis which increases risk of hypoperfusion in specific areas of the brain called watershed regions. Using diffusion weighted magnetic resonance imaging (dMRI), adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) in their white matter compared to controls. These areas of white matter alterations have been associated with cognitive deficits as well. To our knowledge the examination of combined white matter tracts in the watershed regions of the brain in children with moyamoya has not been previously examined. Hypothesis: We hypothesize that children with moyamoya will have higher FA and lower MD and RD in the combined white matter tracts that are in the watershed region compared to control children. Methods: We compared a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke to 25 children controls. We analyzed dMRI data using an unscented Kalman filter (UKF) tractography method and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, axial diffusivity (AD), and RD of the combined watershed white matter tracts using co-variate adjusted ANOVA. Results: Age and sex were not significantly different between children with moyamoya and controls. For the combined watershed white matter tracts, children with moyamoya had significantly lower FA and higher MD and RD. AD was also higher but not significant compared to control children (Table 1). Conclusion: Lower FA with higher MD and RD is consistent with alterations in white matter tracts concerning for unrecognized white matter injury from hypoperfusion. These dMRI findings could be used as a biomarker for children with moyamoya at risk for cognitive deficits due to hypoperfusion.

Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19.

We aimed to compare brain white matter integrity in participants with post-COVID-19 conditions (PCC) and healthy controls. We compared cognitive performance (NIH Toolbox®), psychiatric symptoms and diffusion tensor imaging (DTI) metrics between 23 PCC participants and 24 controls. Fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities were measured in 9 white matter tracts and 6 subcortical regions using MRICloud. Compared to controls, PCC had similar cognitive performance, but greater psychiatric symptoms and perceived stress, as well as higher FA and lower diffusivities in multiple white matter tracts (ANCOVA-p-values≤0.001-0.048). Amongst women, PCC had higher left amygdala-MD than controls (sex-by-PCC p=0.006). Regardless of COVID-19 history, higher sagittal strata-FA predicted greater fatigue (r=0.48-0.52, p<0.001) in all participants, and higher left amygdala-MD predicted greater fatigue (r=0.61, p<0.001) and anxiety (r=0.69, p<0.001) in women, and higher perceived stress (r=0.45, p=0.002) for all participants. Microstructural abnormalities are evident in PCC participants averaged six months after COVID-19. The restricted diffusivity (with reduced MD) and higher FA suggest enhanced myelination or increased magnetic susceptibility from iron deposition, as seen in stress conditions. The higher amygdala-MD in female PCC suggests persistent neuroinflammation, which might contribute to their fatigue, anxiety, and perceived stress.

Diffusion Tensor Imaging for Interpreting Fractional Anisotropy and Mean Diffusivity in Normal-appearing White Matter of Patients with HIV-associated Neurocognitive Disorders: A Case-control Study

Introduction: {Human Immunodeficiency Virus (HIV)-associated Neurocognitive Disorder (HAND)} affects the everyday functioning of patients. It is usually difficult to diagnose HAND in the outpatient setting as detailed neuropsychological performance testing, such as the International HIV Dementia Scale (IHDS), is required. Neuroimaging techniques hold great promise in the early diagnosis and management of HAND, but there is a paucity of studies on the evaluation of HAND using Diffusion Tensor Imaging (DTI) in the Indian population. Aim: To investigate DTI and interpret Fractional Anisotropy (FA) and Mean Diffusivity (MD) values in the White Matter (WM) of patients with HAND and compare them with age and sex- matched controls. Materials and Methods: A case-control study was conducted at the Department of Radiodiagnosis, ABVIMS and Dr. RML Hospital, New Delhi, India, from January 2021 to May 2022. Thirty subjects (15 cases and 15 controls) were included. HIV-positive patients underwent the IHDS to assess cognitive impairment. Magnetic Resonance Imaging (MRI) examination was performed at three tesla using conventional sequences, and DTI was applied. Maps of FA and MD values were generated. Mean FA and MD values of normal-appearing white matter tracts between cases and controls were compared using a t-test. Spearman's correlation test was applied to assess the correlation between IHDS scores and DTI parameters. Results: The majority of cases in the study were in the age group of 31-40 years, and the mean age of cases was 41.27±11.16 years. The present study revealed significantly lower FA values compared to controls in bilateral Frontal WM, Parieto-occipital WM, genu of the Corpus Callosum (CC), right hippocampal WM, and right corona radiata. The mean MD of bilateral Frontal WM, Parieto-occipital WM, corona radiata, and Hippocampal WM was significantly increased in cases compared to healthy controls. A significant association was found between the IHDS score and FA values of the genu of the CC (rho= 0.7), right corona radiata (rho= 0.7), right Hippocampal WM (rho= 0.9), and MD of the left Parieto-occipital WM (rho= -0.6), and left hippocampal WM (rho= -0.5). Conclusion: Diffusion tensor MR imaging can detect abnormalities that are missed by routine MR imaging. DTI provides a valuable marker to monitor HIV-associated Central Nervous System (CNS) injury, which can lead to neurocognitive impairment.

Longitudinal associations between adolescent catch-up sleep, white-matter maturation and internalizing problems

Sleep is an important contributor for neural maturation and emotion regulation during adolescence, with long-term effects on a range of white matter tracts implicated in affective processing in at-risk populations. We investigated the effects of adolescent sleep patterns on longitudinal changes in white matter development and whether this is related to the emergence of emotional (internalizing) problems. Sleep patterns and internalizing problems were assessed using self-report questionnaires in adolescents recruited in the general population followed up from age 14–19 years (N = 111 White matter structure was measured using diffusion tensor imaging (DTI) and estimated using fractional anisotropy (FA). We found that longitudinal increases in time in bed (TIB) on weekends and increases in TIB-variability between weekdays to weekend, were associated with an increase in FA in various interhemispheric and cortico-striatal tracts. Extracted FA values from left superior longitudinal fasciculus mediated the relationship between increases in TIB on weekends and a decrease in internalizing problems. These results imply that while insufficient sleep might have potentially harmful effects on long-term white matter development and internalizing problems, longer sleep duration on weekends (catch-up sleep) might be a natural counteractive and protective strategy.

Brain recovery of the NAc fibers and prediction of craving changes in person with heroin addiction: A longitudinal study

BackgroundProgress have been made in brain function recovery after long-term abstinence in person with heroin addiction (PHA). However, less is known about whether the nucleus accumbens (NAc) white matter pathways can recover in PHA by prolonged abstinence. MethodsForty-two PHA and Thirty-nine age- and gender- matched healthy controls (HCs) were recruited. Two MRI scans were obtained at baseline (PHA1) and 8-month follow-up (PHA2). We employed tractography atlas-based analysis (TABS) method to investigate fractional anisotropy (FA) changes in NAc fiber tracts (i.e., Insula-NAc, ventral tegmental area (VTA)-NAc, medial prefrontal cortex (MPFC)-NAc) in PHA. A partial least square regression (PLSR) analysis was carried to explore whether FA of NAc fiber tracts can predict longitudinal craving changes. ResultsRelative to HCs, lower FA was found in the right Insula-NAc and VTA-NAc fiber tracts in PHA1, and PHA2 showed increased FA values in these tracts compared with PHA1. Furthermore, changes of FA of NAc fiber tracts can predict longitudinal craving changes (r = 0.51). Additionally, craving changes can also be predicted from FA changes in the left Insula-NAc (r = 0.601) and VTA-NAc (r = 0.384) fiber alone. ConclusionsResults indicated that the right Insula-NAc and VTA-NAc fiber tracts are potential biomarkers for brain recovery. Prediction of craving changes highlighted the utility of structural markers to inform clinical decision-making of treatment for PHA.

Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease

BackgroundMagnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back.MethodsIn this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z-scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z-scores, with gradients hypothesised to represent directionality of neurodegeneration.ResultsAt group-level, z-scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient − 0.24, [95% CI − 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001).DiscussionAnalysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.

Differential association of antioxidative defense genes with white matter integrity in youth bipolar disorder

Oxidative stress is associated with white matter diffusion metrics in adults with bipolar disorder (BD). We examined the association of single-nucleotide polymorphisms in the oxidative stress system, superoxide dismutase-2 (SOD2) rs4880 and glutathione peroxidase-3 (GPX3) rs3792797 with fractional anisotropy (FA) and radial diffusivity (RD) in youth with BD. Participants included 104 youth (age 17.5 ± 1.7 years; 58 BD, 46 healthy controls). Saliva samples were obtained for genotyping, and diffusion tensor imaging was acquired. Voxel-wise whole-brain white matter diffusion analyses controlled for age, sex, and race. There were significant diagnosis-by-SOD2 rs4880 interaction effects for FA and RD in major white matter tracts. Within BD, the group with two copies of the G-allele (GG) showed lower FA and higher RD than A-allele carriers. Whereas within the control group, the GG group showed higher FA and lower RD than A-allele carriers. Additionally, FA was higher and RD was lower within the control GG group compared to the BD GG group. No significant findings were observed for GPX3 rs3793797. The current study revealed that, within matter tracts known to differ in BD, associations of SOD2 rs4880 GG genotype with both FA and RD differed between BD vs healthy control youth. The SOD2 enzyme encoded by the G-allele, has higher antioxidant capacity than the enzyme encoded by the A-allele. We speculate that the current findings of lower FA and higher RD of the BD GG group compared to the other groups reflects attenuation of the salutary antioxidant effects of GG genotype on white matter integrity in youth with BD, in part due to predisposition to oxidative stress. Future studies incorporating other genetic markers and oxidative stress biomarkers are warranted.

White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: A pooled case–control study

ABSTRACT Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population.

P.217 Cervical spinal cord MRI parameters as predictors of early degeneration in asymptomatic C9Orf72 carriers: a longitudinal study.

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) share genetic susceptibility and a large portion of familial cases are due to <i>C9orf72</i> gene mutations. Brain and spinal cord (SC) imaging studies in asymptomatic <i>C9orf72</i> carriers have demonstrated white (WM) and grey matter (GM) degeneration up to 20 years before the expected symptom onset. The objective of this study is to longitudinally describe, using quantitative MRI, the evolution of SC degeneration over 36 months' observation in a cohort of asymptomatic <i>C9orf72</i> mutation carriers. 40 asymptomatic <i>C9orf72</i> carriers (C9+) and 32 non-mutated healthy controls were enrolled in the study. Each subject underwent a 3T cervical SC MRI at baseline, after 18 and 36 months. Quantitative measures of GM and WM atrophy and DTI parameters (FA, AD, MD, RD) in the cortico-spinal tracts (CSTs) were computed. We used linear mixed-effects models to test for significant differences in MRI parameters between time points. Time point, baseline age, gender, genetic status and interaction terms between time point and age, and between time point and genetic status were considered as fixed effects. Multivariate linear regression was used to test if MRI parameters are capable of predict genetic status of the subjects. Sex and family phenotype (ALS or FTD) were used as covariates. Mean age at inclusion was 41.18 years +/- 11.46. No significant difference in GM and WM cross-sectional area was observed over the three time points in C9+ subjects. A significant progressive reduction of fractional anisotropy (FA) in the CSTs was observed over time with a significant difference between the baseline and the 36-months evaluation (p = 0.04). No other significant modifications in DTI parameters were detected. FA in the CSTs was also the only significant parameter in a multivariate model predicting mutation status of the study subjects (p = 0.03). Cervical SC imaging of <i>C9orf72</i> hexanucleotide carriers detect a progressive pyramidal tract FA reduction which seems to be continuous but not linear. CSTs degeneration as described by FA decrease also allows to identify C9+ carriers, suggesting that it could be a useful parameter for early diagnosis of the disease.

DTI Connectometry Analysis Reveals White Matter Changes in Cognitively Impaired World Trade Center Responders at Midlife.

More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD). To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders. 99 WTC responders (mean age 56 years) consisting of CI-/PTSD- (n = 27), CI+/PTSD- (n = 25), CI-/PTSD+ (n = 24), and CI+/PTSD+ (n = 23) were matched on age, sex, occupation, race, and education. Cognitive status was determined using the Montreal Cognitive Assessment and PTSD status was determined using the DSM-IV SCID. Diffusion tensor imaging was acquired on a 3T Siemens Biograph mMR scanner. Connectometry analysis was used to examine whole-brain tract-level differences in white matter integrity as reflected by fractional anisotropy (FA) values after adjusting for confounders. Analyses identified that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum and the right uncinate fasciculus. Furthermore, FA was negatively correlated with PTSD status, regardless of CI status in the superior thalamic radiation and the cerebellum. This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.

Blood pressure changes impact corticospinal integrity and downstream gait and balance control

Blood pressure (BP) plays an important role in white matter integrity. We sought to determine the role of intra-individual BP changes on white matter and evaluate the impact on gait speed and imbalance by sex. We identified 990 eligible participants in the population-based Mayo Clinic Study of Aging and analyzed fractional anisotropy (FA) in white matter regions. Using structural equation models (SEM), we assessed the effect of BP slope on corticospinal tract (CST) FA and downstream effects on gait speed and imbalance after age and sex effects. Of 990 participants, 438 (44%) were female with mean age of 76 years. In linear models predicting CST FA, a greater change in BP slope (0.0004; p = 0.026) and female sex (0.017; p < 0.001) were significant predictors of lower CST FA. SEMs showed that older age, female sex, and higher BP slope predicted lower CST FA, and lower CST FA predicted worse downstream motor control. Therefore, intra-individual BP slope and variability impact corticospinal tract microstructural properties of white matter with females having increased susceptibility to damage.

Structural Covariance and Heritability of the Optic Tract and Primary Visual Cortex in Living Human Brains.

Individual differences among human brains exist at many scales, spanning gene expression, white matter tissue properties, and the size and shape of cortical areas. One notable example is an approximately 3-fold range in the size of human primary visual cortex (V1), a much larger range than is found in overall brain size. A previous study (Andrews et al., 1997) reported a correlation between optic tract (OT) cross-section area and V1 size in postmortem human brains, suggesting that there may be a common developmental mechanism for multiple components of the visual pathways. We evaluated the relationship between properties of the OT and V1 in a much larger sample of living human brains by analyzing the Human Connectome Project (HCP) 7 Tesla Retinotopy Dataset (including 107 females and 71 males). This dataset includes retinotopic maps measured with functional MRI (fMRI) and fiber tract data measured with diffusion MRI (dMRI). We found a negative correlation between OT fractional anisotropy (FA) and V1 surface area (r = -0.19). This correlation, although small, was consistent across multiple dMRI datasets differing in acquisition parameters. Further, we found that both V1 surface area and OT properties were correlated among twins, with higher correlations for monozygotic (MZ) than dizygotic (DZ) twins, indicating a high degree of heritability for both properties. Together, these results demonstrate covariation across individuals in properties of the retina (OT) and cortex (V1) and show that each is influenced by genetic factors.SIGNIFICANCE STATEMENT The size of human primary visual cortex (V1) has large interindividual differences. These differences do not scale with overall brain size. A previous postmortem study reported a correlation between the size of the human optic tract (OT) and V1. In this study, we evaluated the relationship between the OT and V1 in living humans by analyzing a neuroimaging dataset that included functional MRI (fMRI) and diffusion MRI (dMRI) data. We found a small, but robust correlation between OT tissue properties and V1 size, supporting the existence of structural covariance between the OT and V1 in living humans. The results suggest that characteristics of retinal ganglion cells (RGCs), reflected in OT measurements, are correlated with individual differences in human V1.

602-P: Prenatal Exposure to Gestational Diabetes Mellitus and Autistic Traits among Typically Developing Children

Children exposed to GDM in utero are at increased risk of developing autism spectrum disorder, a neurodevelopmental disorder characterized by social deficits. Limited studies have tested if GDM exposure is associated with higher autistic traits in typically developing children or what the neural substrates are. We used the social responsiveness scale (SRS) to measure differences in autistic traits between GDM-exposed and unexposed children and examined if white matter pathways involved in the social brain network (SBN) were related to autistic traits in children. Children were recruited from Kaiser Permanente Southern California to participate in BrainChild, a study assessing neural programming of disease risk (N=136; 9 ±1.5 years; 63% female; 52% GDM-exposed) . During visits, children completed a brain magnetic resonance imaging scan, demographics were collected, and parents completed the SRS. Maternal GDM diagnosis, glucose levels from a 1-hr 50g glucose challenge completed during pregnancy, and pre-pregnancy BMI were obtained from electronic medical records. Fractional anisotropy (FA) was used to assess white matter microstructure. Linear regression was used to test associations between SRS raw scores with GDM exposure, maternal glucose levels, and SBN white matter pathways, controlling for child age, sex, socioeconomic status, and maternal pre-pregnancy BMI. SRS scores were higher for GDM-exposed children than unexposed (GDM: 35.7±2.1; Unexposed: 29.5±2.3, p=0.03) . Maternal glucose levels were associated with higher child SRS scores (β=0.002, p=0.06) . Higher SRS scores were associated with reduced FA in multiple SBN white matter tracts (p&amp;lt;0.01) . GDM exposure and higher maternal glucose levels were associated with more autistic traits, suggesting that intrauterine exposure to a GDM hyperglycemic environment may affect autistic traits even among typically developing children. Further, SBN white matter tracts may be related to social deficits. Disclosure J.M.Alves: None. B.C.Angelo: None. S.Negriff: None. S.H.Luo: None. T.Chow: None. R.Cabeen: None. S.A.Carter: None. A.Xiang: None. K.A.Page: None. Funding pAmerican Diabetes Association (#1-14-ACE-36) ; R01DK116858

Longer screen time utilization is associated with the polygenic risk for Attention-deficit/hyperactivity disorder with mediation by brain white matter microstructure.

SummaryBackgroundAttention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset.MethodsLeveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9–11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses.FindingsChildren with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU.InterpretationThese findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU.FundingThis study was mainly supported by NSFC and National Key R&D Program of China.

Cardiorespiratory Fitness Is Associated With Better White Matter Integrity in Persons Living With HIV.

Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffusion basis spectrum imaging measure HIV-related changes in brain white matter integrity. We used these measures of structural brain integrity to assess white matter changes, physical fitness, and cognition in a cross-sectional study of PLWH. Forty-four virologically well-controlled PLWH were recruited (average age of 56 years, a median recent CD4+ count of 682 cells/mm3). Diffusion tensor imaging -derived fractional anisotropy (FA) and diffusion basis spectrum imaging-derived axonal density were calculated. Cardiorespiratory fitness [maximal volume of oxygen consumption (VO2 max)] was measured by performing indirect calorimetry during exercise to volitional exhaustion. Cardiovascular risk was assessed by the Framingham risk score. Neuropsychological performance (NP) testing evaluated learning, memory, psychomotor/processing speed, and executive function. Partial correlations assessed the relationships among cardiorespiratory fitness, neuroimaging, NP, and HIV clinical metrics (CD4+ count and time since diagnosis). Higher VO2 max was associated with higher FA and higher axonal density in multiple white matter tracts, including the corticospinal tract and superior longitudinal fasciculus. Better NP in the motor/psychomotor domain was positively associated with FA and axonal density in diverse tracts including those associated with motor and visuospatial processing. However, higher VO2 max was not associated with NP or HIV clinical metrics. An active lifestyle promoting cardiorespiratory fitness may lead to better white matter integrity and decreased susceptibility to cognitive decline in virologically well-controlled PLWH.

A Diffusion Tensor Imaging Analysis of Frontal Lobe White Matter Microstructure in Trigonocephaly Patients

BackgroundChildren with trigonocephaly are at risk for neurodevelopmental disorders. The aim of this study is to investigate white matter properties of the frontal lobes in young, unoperated patients with metopic synostosis as compared to healthy controls using diffusion tension imaging (DTI). MethodsPreoperative DTI data sets of 46 patients with trigonocephaly with a median age of 0.49 (interquartile range: 0.38) years were compared with 21 controls with a median age of 1.44 (0.98) years. White matter metrics of the tracts in the frontal lobe were calculated using FMRIB Software Library (FSL). The mean value of tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were estimated for each subject and compared to healthy controls. By linear regression, FA and MD values per tract were assessed by trigonocephaly, sex, and age. ResultsThe mean FA and MD values in the frontal lobe tracts of untreated trigonocephaly patients, younger than 3 years, were not significantly different in comparison to controls, where age showed to be a significant associated factor. ConclusionsMicrostructural parameters of white matter tracts of the frontal lobe of patients with trigonocephaly are comparable to those of controls aged 0-3 years.

Normal-Appearing White Matter Deteriorates over the Year After an Ischemic Stroke and Is Associated with Global Cognition.

Normal-appearing white matter (NAWM) is a hub of plasticity, but data relating to its influence on post-ischemic stroke (IS) outcome remain scarce. The aim of this study was to evaluate the relationship between NAWM integrity and cognitive outcome after an IS. A longitudinal study was conducted including supra-tentorial IS patients. A 3-Tesla brain MRI was performed at baseline and 1year, allowing the analyses of mean fractional anisotropy (FA) and mean diffusivity (MD) in NAWM masks, along with the volume of white matter hyperintensities (WMH) and IS. A Montreal Cognitive Assessment (MoCA), an Isaacs set test, and a Zazzo's cancellation task were performed at baseline, 3months and 1year. Mixed models were built, followed by Tract-based Spatial Statistics (TBSS) analyses. Ninety-five patients were included in the analyses (38% women, median age 69 ± 20). FA significantly decreased, and MD significantly increased between baseline and 1year, while cognitive scores improved. Patients who decreased their NAWM FA more over the year had a slower cognitive improvement on MoCA (β = - 0.11, p = 0.05). The TBSS analyses showed that patients who presented the highest decrease of FA in various tracts of white matter less improved their MoCA performances, regardless of WMH and IS volumes, demographic confounders, and clinical severity. NAWM integrity deteriorates over the year after an IS, and is associated with a cognitive recovery slowdown. The diffusion changes recorded here in patients starting with an early preserved white matter structure could have long term impact on cognition.

A large-scale investigation of white matter microstructural associations with reading ability

Reading involves the functioning of a widely distributed brain network, and white matter tracts are responsible for transmitting information between constituent network nodes. Several studies have analyzed fiber bundle microstructural properties to shed insights into the neural basis of reading abilities and disabilities. Findings have been inconsistent, potentially due to small sample sizes and varying methodology. To address this, we analyzed a large data set of 686 children ages 5–18 using state-of-the-art neuroimaging acquisitions and processing techniques. We searched for associations between fractional anisotropy (FA) and single-word and single-nonword reading skills in children with diverse reading abilities across multiple tracts previously thought to contribute to reading. We also looked for group differences in tract FA between typically reading children and children with reading disabilities. FA of the white matter increased with age across all participants. There were no significant correlations between overall reading abilities and tract FAs across all children, and no significant group differences in tract FA between children with and without reading disabilities. There were associations between FA and nonword reading ability in older children (ages 9 and above). Higher FA in the right superior longitudinal fasciculus (SLF) and left inferior cerebellar peduncle (ICP) correlated with better nonword reading skills. These results suggest that letter-sound correspondence skills, as measured by nonword reading, are associated with greater white matter coherence among older children in these two tracts, as indexed by higher FA.

White matter microstructure associated with anhedonia among individuals with bipolar disorders and high-risk for bipolar disorders

BackgroundAnhedonia - a key symptom of depression - is highly associated with poorer outcomes and suicidal behavior. Alterations in the circuitry of reward-related brain regions have been robustly associated with anhedonia in unipolar depression, but not bipolar disorder (BD). We investigated white matter microstructures associated with anhedonia in participants with BD types I and II and first-degree relatives of patients with BD (BD-siblings). MethodsEighty participants (BD types I and II: 56 [70%], and BD-siblings: 24 [30%]) underwent diffusion tensor imaging (DTI); Fractional anisotropy (FA) of different tracts were computed. Anhedonia was assessed using item 8, (“inability to feel'') of the MADRS scale. General linear models were used to compare the FA of different tracts in participants with and without anhedonia controlling for several clinical and demographic variables. ResultsThe mean age of the sample was 37 (± 11) years old, and 68.8% were female. Participants with anhedonia (32.5%) presented lower mean FA in the left uncinate fasciculus (UF) (p = 0.005), right temporal endings of the superior longitudinal fasciculus (SLFT) (p = 0.04), and in the left and right parietal endings of the superior longitudinal fasciculus (SLFP) (p = 0.003, and p = 0.04, respectively). Similar comparisons between participants with or without current depressive episodes and between participants with or without inner tension according to the MADRS did not show significant differences, specificity of the findings for anhedonia. ConclusionsLower FA in the left UF and SLF are potential neuroimaging markers of anhedonia in individuals with BD and high-risk for BD.

Baseline associations of cardiometabolic risk factors, executive function, and white matter microstructure in the DIRECT‐PLUS trial

AbstractBackgroundCardiometabolic risk factors including mid‐life obesity, diabetes and hypertension are associated with accelerated cognitive decline, e.g. in executive function, and brain aging, e.g. alterations in white matter (WM) microstructure [1].Method290 participants (34 females, mean age= 49 y (30 – 79 y) of the DIRECT‐PLUS trial (clinicaltrials.gov ID: NCT03020186, [2]) participated in diffusion‐weighted imaging on a 3T Philips. Tract‐based spatial statistics provided hemisphere‐averaged fractional anisotropy (FA) of 9 fiber tracts (genu/body of corpus callosum, body and crus of fornix, (hippocampal) cingulum, inferior/superior longitudinal fasciculus (i/sLF) and uncinate fasciculus. We tested the association of age, sex, five risk factors (body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin, high and low‐density lipoprotein), four measures of executive function from the brief executive function battery and average FA of these WM tracts with correlations and linear regression models, adjusting for age and sex, in R version 3.6.1, corrected for multiple testing using false discovery rate (FDR).ResultAge was associated with lower FA in the cingulum (r=‐0.56, p&lt;0.001), uncinate fasciculus (r=‐0.51, p&lt;0.001), hippocampus cingulum (r=‐0.39, p&lt;0.001), iLF (‐0.19, p=0.001) and sLF (r=‐0.18, p=0.001). FA in the fornix, hippocampus cingulum and iLF were higher in men as compared to women (p&lt;0.05 for all). Among cardiometabolic risk factors, higher BMI was associated with significantly lower FA in iILF (β = ‐0.002, p=0.0009, padj=0.035), and higher SBP was associated with lower FA in uncinate fasciculus (β= ‐0.0006, p=0.0012, padj=0.035)None of the executive function measures was significantly related to FA of WM tracts after adjusting for age and sex and controlling for FDR.ConclusionOur findings corroborate previous findings of the adverse impacts of cardiometabolic risk on WM microstructure. Upcoming longitudinal investigations in this dataset will show whether improved cardiometabolic function, induced by a dietary intervention, will modify the trajectories of WM microstructure and cognitive performance. Figure 1: Higher BMI and higher SBP were significantly associated with lower FA in two major WM tracts (blue: ILF, green: uncinate fasciculus)[1] Wassenaar, TM., et al. NBA (2019) [2] Tsaban, G, et al. Heart (2020).