Brain White Matter Microstructure Research Articles

Microstructural changes of the white matter in systemic lupus erythematosus patients without neuropsychiatric symptoms: a multi-shell diffusion imaging study

BackgroundDiffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide more comprehensive and informative perspective on microstructural alterations of cerebral white matter (WM) than single-shell diffusion tensor imaging (DTI), especially in the detection of crossing fiber. However, studies on systemic lupus erythematosus patients without neuropsychiatric symptoms (non-NPSLE patients) using multi-shell diffusion imaging remain scarce.MethodsTotally 49 non-NPSLE patients and 41 age-, sex-, and education-matched healthy controls underwent multi-shell diffusion magnetic resonance imaging. Totally 10 diffusion metrics based on DKI (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis and radial kurtosis) and NODDI (neurite density index, orientation dispersion index and volume fraction of the isotropic diffusion compartment) were evaluated. Tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analyses were performed to determine group differences in brain WM microstructure. The associations of multi-shell diffusion metrics with clinical indicators were determined for further investigation.ResultsTBSS analysis revealed reduced FA, AD and RK and increased ODI in the WM of non-NPSLE patients (P < 0.05, family-wise error corrected), and ODI showed the best discriminative ability. Atlas-based ROI analysis found increased ODI values in anterior thalamic radiation (ATR), inferior frontal-occipital fasciculus (IFOF), forceps major (F_major), forceps minor (F_minor) and uncinate fasciculus (UF) in non-NPSLE patients, and the right ATR showed the best discriminative ability. ODI in the F_major was positively correlated to C3.ConclusionThis study suggested that DKI and NODDI metrics can complementarily detect WM abnormalities in non-NPSLE patients and revealed ODI as a more sensitive and specific biomarker than DKI, guiding further understanding of the pathophysiological mechanism of normal-appearing WM injury in SLE.

Distinct Longitudinal Brain White Matter Microstructure Changes and Associated Polygenic Risk of Common Psychiatric Disorders and Alzheimer’s Disease in the UK Biobank

BackgroundDuring the course of adulthood and aging, white matter (WM) structure and organization are characterized by slow degradation processes such as demyelination and shrinkage. An acceleration of such aging processes has been linked to the development of a range of diseases. Thus, an accurate description of healthy brain maturation, particularly in terms of WM features, is fundamental to the understanding of aging. MethodsWe used longitudinal diffusion magnetic resonance imaging to provide an overview of WM changes at different spatial and temporal scales in the UK Biobank (UKB) (n = 2678; agescan 1 = 62.38 ± 7.23 years; agescan 2 = 64.81 ± 7.1 years). To examine the genetic overlap between WM structure and common clinical conditions, we tested the associations between WM structure and polygenic risk scores for the most common neurodegenerative disorder, Alzheimer’s disease, and common psychiatric disorders (unipolar and bipolar depression, anxiety, obsessive-compulsive disorder, autism, schizophrenia, attention-deficit/hyperactivity disorder) in longitudinal (n = 2329) and cross-sectional (n = 31,056) UKB validation data. ResultsOur findings indicate spatially distributed WM changes across the brain, as well as distributed associations of polygenic risk scores with WM. Importantly, brain longitudinal changes reflected genetic risk for disorder development better than the utilized cross-sectional measures, with regional differences giving more specific insights into gene-brain change associations than global averages. ConclusionsWe extend recent findings by providing a detailed overview of WM microstructure degeneration on different spatial levels, helping to understand fundamental brain aging processes. Further longitudinal research is warranted to examine aging-related gene-brain associations.

Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women.

Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.

Association of Blood Pressure With Brain White Matter Microstructural Integrity Assessed With MRI Diffusion Tensor Imaging in Healthy Young Adults.

High blood pressure (BP) in middle-aged and older adults is associated with a brain white matter (WM) microstructural abnormality. However, little evidence is available in healthy young adults. We investigated the associations between high BP and WM microstructural integrity in young adults. This study included 1015 healthy young adults (542 women, 22-37 years) from the Human Connectome Project. Brachial systolic and diastolic BP were measured using a semiautomatic or manual sphygmomanometer. Diffusion-weighted magnetic resonance imaging was acquired to obtain diffusion tensor imaging metrics of free water (FW) content, FW-corrected WM fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Using whole-brain voxel-wise linear regression models and ANCOVA, we examined associations of BP and hypertension stage with diffusion tensor imaging metrics after adjusting for age, sex, education, body mass index, smoking status, alcohol consumption history, and differences in the b value used for diffusion magnetic resonance imaging. Systolic and diastolic BP of the sample (mean±SD) were 122.8±13.0 and 76.0±9.9 mm Hg, respectively. Associations of BP with diffusion tensor imaging metrics revealed regional heterogeneity for FW-corrected fractional anisotropy. High BP and high hypertension stage were associated with higher FW and lower FW-corrected axial diffusivity, FW-corrected radial diffusivity, and FW-corrected mean diffusivity. Moreover, associations of high diastolic BP and hypertension stage with high FW were found only in men not in women. High BP in young adults is associated with altered brain WM microstructural integrity, suggesting that high BP may have damaging effects on brain WM microstructural integrity in early adulthood, particularly in men.

Mapping tissue microstructure of brain white matter in vivo in health and disease using diffusion MRI

Abstract Diffusion magnetic resonance imaging offers unique in vivo sensitivity to tissue microstructure in brain white matter, which undergoes significant changes during development and is compromised in virtually every neurological disorder. Yet, the challenge is to develop biomarkers that are specific to micrometer-scale cellular features in a human MRI scan of a few minutes. Here, we quantify the sensitivity and specificity of a multicompartment diffusion modeling framework to the density, orientation, and integrity of axons. We demonstrate that using a machine learning-based estimator, our biophysical model captures the morphological changes of axons in early development, acute ischemia, and multiple sclerosis (total N = 821). The methodology of microstructure mapping is widely applicable in clinical settings and in large imaging consortium data to study development, aging, and pathology.

Interactions between overweight/obesity and alcohol dependence impact human brain white matter microstructure: evidence from DTI.

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

Urban environment during pregnancy and childhood and white matter microstructure in preadolescence in two European birth cohorts

Growing evidence suggests that urban environment may influence cognition and behavior in children, but the underlying pollutant and neurobiological mechanisms are unclear. We evaluated the association of built environment and urban natural space indicators during pregnancy and childhood with brain white matter microstructure in preadolescents, and examined the potential mediating role of air pollution and road-traffic noise. We used data of the Generation R Study, a population-based birth cohort in Rotterdam, the Netherlands (n = 2725; 2002–2006) for the primary analyses. Replication of the main findings was attempted on an independent neuroimaging dataset from the PELAGIE birth cohort, France (n = 95; 2002–2006). We assessed exposures to 12 built environment and 4 urban natural spaces indicators from conception up to 9 years of age. We computed 2 white matter microstructure outcomes (i.e., average of fractional anisotropy (FA) and mean diffusivity (MD) from 12 white matte tracts) from diffusion tensor imaging data. Greater distance to the nearest major green space during pregnancy was associated with higher whole-brain FA (0.001 (95%CI 0.000; 0.002) per 7 m increase), and higher land use diversity during childhood was associated with lower whole-brain MD (−0.001 (95%CI -0.002; −0.000) per 0.12-point increase), with no evidence of mediation by air pollution nor road-traffic noise. Higher percentage of transport and lower surrounding greenness during pregnancy were associated with lower whole-brain FA, and road-traffic noise mediated 19% and 52% of these associations, respectively. We found estimates in the same direction in the PELAGIE cohort, although confidence intervals were larger and included the null. This study suggests an association between urban environment and white matter microstructure, mainly through road-traffic noise, indicating that greater access to green space nearby might promote white matter development.

Diffusion kurtosis imaging of brain white matter alteration in patients with coronary artery disease based on the TBSS method.

The aim of our study was to examine the alterations in microstructure in patients with coronary artery disease (CAD) and cognitive impairment (CI) using diffusion kurtosis imaging (DKI). Additionally, we aimed to investigate the potential correlation between DKI parameters and cognitive function. A total of 28 CAD patients and 30 healthy controls (HC) were prospectively enrolled in our study. All participants underwent routine and diffusion sequences of head imaging. DKE software was utilized to generate various diffusion kurtosis imaging parameters (DKI), including kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD). Nonparametric tests were conducted using tract-based spatial statistics (TBSS) to compare the parameter values between the two groups. The parameter values of the significantly different fiber tracts were extracted and correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Compared to the HC group, patients with coronary artery disease exhibited significant reductions in FA values in the bilateral Superior corona radiata, bilateral Anterior corona radiata, bilateral Posterior corona radiata, corpus callosum, left Posterior thalamic radiation, right Posterior limb of internal capsule, Anterior limb of internal capsule, and Cerebral peduncle, as well as in the left Superior longitudinal fasciculus. Additionally, KFA values decreased in the bilateral Anterior corona radiata, bilateral Anterior limb of internal capsule, and Genu of the corpus callosum. The MK values decreased in the right Posterior corona radiata, Retrolenticular part of the internal capsule, Posterior thalamic radiation (including optic radiation), Superior longitudinal fasciculus, and left Posterior thalamic radiation (including optic radiation). Moreover, the RK values decreased in the bilateral Retrolenticular part of the internal capsule, right Posterior thalamic radiation (including optic radiation), and Superior longitudinal fasciculus, as well as in the left Superior longitudinal fasciculus and Posterior thalamic radiation (including optic radiation) (p < 0.01, TFCE corrected), while no significant differences were observed in other parameter values (p > 0.01, TFCE corrected). The FA values of the right posterior limb of the internal capsule (r = 0.610, p = 0.001) and the right cerebral peduncle (r = 0.622, p < 0.001) were positively correlated with MMSE scores. Additionally, a significant correlation between kurtosis and diffusion coefficient parameters (FA and KFA) was observed. CAD patients showed radial shrinkage and complexity of brain white matter microstructure. Whole-brain white matter analysis based on TBSS DKI can objectively reflect the characteristics of white matter damage in CAD patients, providing a basis for the auxiliary diagnosis of CAD with CI.

Fronto-limbic white matter microstructural changes in psychiatrically healthy adults with childhood trauma.

Childhood trauma (CT) may influence brain white matter microstructure; however, few studies have examined the differential impact of distinct CT types on white matter microstructure in psychiatrically healthy adults living in a developing country. In adults without significant medical or psychiatric disorders, we investigated the association(s) between CT, including abuse and neglect, and fractional anisotropy (FA) of limbic tracts previously shown to be associated with CT. Participants underwent diffusion tensor imaging and completed the Childhood Trauma Questionnaire. Multivariate analysis of variance models were used to test the effects of total overall CT, as well as CT subtypes, on FA in six fronto-limbic tracts, adjusting for age, sex, and educational level. The final sample included 69 adults (age 47 ± 17 years; 70% female). Overall, CT had a significant main effect on FA for tracts of interest (p < .001). Greater CT severity was associated with lower FA for the bilateral and left stria terminalis (uncorrected) as well as the bilateral, left, and right anterior limb of the internal capsule (ALIC; corrected). Exposure to total non-violent/deprivational trauma specifically was associated with lower FA of the bilateral, left, and right ALIC, suggesting that distinct types of CT are associated with differential white matter changes in apparently healthy adults. The ALIC predominantly carries fibers connecting the thalamus with prefrontal cortical regions. Microstructural alterations in the ALIC may be associated with functional brain changes, which may be adaptive or increase the risk of accelerated age-related cognitive decline, maladaptive behaviors, and subsyndromal psychiatric symptoms.

Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents

Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13–15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.

Associations between accelerometer‐based physical activity and brain white matter microstructure: Findings from the population‐based Rhineland Study

AbstractBackgroundWhite matter (WM) integrity declines with age and is affected by neurodegenerative diseases. Physical activity promotes neuronal health in animals, and is associated with WM microstructure metrics in humans. However, previous diffusion tensor imaging (DTI) studies were limited by small sample sizes and subjective questionnaire‐based physical activity assessments. Moreover, recently introduced neurite orientation dispersion and density imaging (NODDI) may offer complementary insights. Therefore, we examined the association between accelerometer‐based physical activity and DTI and NODDI measures of WM microstructure in a large population‐based cohort.MethodWe analyzed data of 2,455 participants (57.9% women, mean age: 54.7 years) with valid physical activity and MRI measurements from the Rhineland Study, a prospective cohort study in Bonn, Germany. We recorded physical activity using accelerometers and derived metabolic equivalent (MET)‐hours, step counts and time spent performing sedentary, light‐intensity and moderate‐to‐vigorous (MVPA) activities. DTI (fractional anisotropy (FA), mean diffusivity) and NODDI (orientation dispersion index, neurite density index) measures were obtained from 3T MR images using the microstructure diffusion toolbox. The association of physical activity with WM microstructure was assessed using multivariate polynomial regression, while adjusting for age, sex, education, body mass index and smoking status.ResultPhysical activity was associated with several global and tract‐specific DTI and NODDI measures. Effects were strongest at low physical activity quantities and weakened at higher levels. While higher MET‐hours, step counts and light and moderate‐to‐vigorous intensity activities were related to greater global FA, sedentary time was associated with reduced FA. We observed the strongest tract‐specific effects for moderate‐to‐vigorous intensity activities on the corpus callosum and corona radiata (standardized effects: MVPA on FA corpus callosum, ßlin = 0.0009 [95% CI: 0.0001; 0.0018] and ßqu = ‐0.0006 [95% CI: ‐0.0011; ‐0.0001]; MVPA on FA corona radiata, ßlin = 0.0011 [95% CI: 0.0001; 0.0021] and ßqu = ‐0.0009 [95% CI: ‐0.0014; ‐0.0003]). We obtained similar results for NODDI measures.ConclusionOur findings suggest that WM microstructure and particularly tracts connecting motor regions profit from physical activity. Sedentary individuals may benefit more from additional physical activity than already active individuals. NODDI metrics provide valuable complementary insights into the effects of physical activity on WM microstructure.

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study

Myelination of human brain white matter (WM) continues into adulthood following birth, facilitating connection within and between brain networks. In vivo MRI studies using diffusion weighted imaging (DWI) suggest microstructural properties of brain WM increase over childhood and adolescence. Although DWI metrics, such as fractional anisotropy (FA), could reflect axonal myelination, they are not specific to myelin and could also represent other elements of WM microstructure, for example, fibre architecture, axon diameter and cell swelling. Little work exists specifically examining myelin development. The T1w/T2w ratio approach offers an alternative non-invasive method of estimating brain myelin. The approach uses MRI scans that are routinely part of clinical imaging and only require short acquisition times. Using T1w/T2w ratio maps from three waves of the Neuroimaging of the Children’s Attention Project (NICAP) [N = 95 (208 scans); 44% female; ages 9.5–14.20 years] we aimed to investigate the developmental trajectories of brain white matter myelin in children as they enter adolescence. We also aimed to investigate whether longitudinal changes in myelination of brain WM differs between biological sex. Longitudinal regression modelling suggested non-linear increases in WM myelin brain wide. A positive parabolic, or U-shaped developmental trajectory was seen across 69 of 71 WM tracts modelled. At a corrected level, no significant effect for sex was found. These findings build on previous brain development research by suggesting that increases in brain WM microstructure from childhood to adolescence could be attributed to increases in myelin.

Total-Body Irradiation Alters White Matter Volume and Microstructural Integrity in Rhesus Macaques

Long-term survivors of brain irradiation can suffer from irreversible injury and cognitive impairment. T1-weighted and diffusion tensor magnetic resonance imaging are used to evaluate brain volumes and white matter (WM) microstructure in neurodevelopmental and neurodegenerative conditions. The goal of this study was to evaluate the long-term effects of single-dose total-body irradiation (TBI) or TBI with 5% partial-body sparing on brain volumetrics and WM integrity in macaques. We utilized MRI scans from a cohort of male rhesus macaques (age range: 3.6-22.8 years), to compare global and regional brain volumes and WM diffusion in survivors of TBI (T1w: n=137, DTI: n=121, dose range: 3.5-10 Gy) against unirradiated controls (T1w: n=48, DTI: n=38). In all ROIs, radiation affected the age-related changes in fractional anisotropy (FA); in general, FA increased across age in both groups, but to a lesser extent in the irradiated group (interaction p-values <0.01). Depending on the ROI, mean diffusivity (MD) decreased or remained the same across age in unirradiated animals, while it increased or did not change in irradiated animals. The increases in MD were driven by changes in radial diffusivity (RD) which followed similar trends across age. Axial diffusivity (AD) did not differ by irradiation status. Age-related changes in relative volumes in controls reflected normal trends in humans with increasing WM and decreasing gray matter (GM) until middle age. Cerebrospinal fluid (CSF) volume did not differ across age in controls. WM volume was lower and CSF volume was higher in young, irradiated macaques. WM volume was similar between groups and CSF volume reduced in older irradiated macaques. GM volume was unaffected by radiation. TBI results in delayed WM expansion and long-term disruption of WM integrity. Diffusion changes suggest that myelin injury in WM is a hallmark of late-delayed radiation induced brain injury.

Associations of Arterial Thickness, Stiffness, and Blood Pressure With Brain Morphology in Early Adolescence: A Prospective Population-Based Study.

Arterial wall thickness and stiffness, and high blood pressure have been repeatedly associated with poorer brain health. However, previous studies largely focused on mid- or late-life stages. It is unknown whether any arterial health-related brain changes may be observable already in adolescence. We examined whether (1) carotid intima-media thickness, (2) carotid distensibility, and (3) systolic blood pressure and diastolic blood pressure, measured at the age of 10 years, were associated with brain volumes and white matter microstructure (ie, fractional anisotropy and mean diffusivity) at the age of 14 years. In addition to cross-sectional analyses, we explored associations with longitudinal change in each brain outcome from 10 to 14 years. Analyses were based on 5341 children from the Generation R Study. Higher diastolic blood pressure was associated with lower total brain volume (β, -0.04 [95% CI, -0.07 to -0.01]) and gray matter volume (β, -0.04 [95% CI, -0.07 to -0.01]) at the age of 14 years, with stronger associations in higher diastolic blood pressure ranges. Similar associations emerged between systolic blood pressure and brain volumes, but these were no longer significant after adjusting for birth weight. No associations were observed between blood pressure and white matter microstructure or between carotid intima-media thickness or distensibility and brain morphology. Arterial blood pressure, but not intima-media thickness and distensibility, is associated with structural neuroimaging markers in early adolescence. Volumetric measures may be more sensitive to these early arterial health differences compared with microstructural properties of the white matter, but further studies are needed to confirm these results and assess potential causal mechanisms.

Size at birth predicts later brain volumes

We aimed to investigate whether gestation at birth, birth weight, and head circumference at birth are still associated with brain volume and white matter microstructure at 9–10 years in children born late-preterm and at term. One hundred and eleven children born at ≥ 36 weeks gestation from the CHYLD Study cohort underwent brain magnetic resonance imaging at 9 to 10 years. Images were analysed using FreeSurfer for volumetric data and tract-based spatial statistics for diffusion data. Of the cohort, 101 children were included for volumetric analysis [boys, 49(49%); median age, 9.5 (range: 8.9–12.4) years]. Shorter gestation at birth, lower birthweight, and smaller birth head circumference were associated with smaller brain volumes at 9 to 10 years, both globally and regionally. Amongst the perinatal factors studied, head circumference at birth was the strongest predictor of later brain volumes. Gestation at birth and absolute birthweight were not associated with diffusion metrics of white matter skeleton. However, lower birthweight z-score was associated with higher fractional anisotropy and lower radial diffusivity. Our findings suggest that even in children born late preterm and at term, growth before birth and timing of birth are still associated with brain development in mid-childhood.

The role of brain white matter in depression resilience and response to sleep interventions.

Insomnia poses a high risk for depression. Brain mechanisms of sleep and mood improvement following cognitive behavioural therapy for insomnia remain elusive. This longitudinal study evaluated whether (i) individual differences in baseline brain white matter microstructure predict improvements and (ii) intervention affects brain white matter microstructure. People meeting the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for Insomnia Disorder (n = 117) participated in a randomized controlled trial comparing 6 weeks of no treatment with therapist-guided digital cognitive behavioural therapy for insomnia, circadian rhythm support or their combination (cognitive behavioural therapy for insomnia + circadian rhythm support). Insomnia Severity Index and Inventory of Depressive Symptomatology-Self Report were assessed at baseline and followed up at Weeks 7, 26, 39 and 52. Diffusion-weighted magnetic resonance images were acquired at baseline and Week 7. Skeletonized white matter tracts, fractional anisotropy and mean diffusivity were quantified both tract-wise and voxel-wise using tract-based spatial statistics. Analyses used linear and mixed effect models while correcting for multiple testing using false discovery rate and Bonferroni for correlated endpoint measures. Our results show the following: (i) tract-wise lower fractional anisotropy in the left retrolenticular part of the internal capsule at baseline predicted both worse progression of depressive symptoms in untreated participants and more improvement in treated participants (fractional anisotropy × any intervention, PFDR = 0.053, Pcorr = 0.045). (ii) Only the cognitive behavioural therapy for insomnia + circadian rhythm support intervention induced a trend-level mean diffusivity decrease in the right superior corona radiata (PFDR = 0.128, Pcorr = 0.108), and individuals with a stronger mean diffusivity decrease showed a stronger alleviation of insomnia (R = 0.20, P = 0.035). In summary, individual differences in risk and treatment-supported resilience of depression involve white matter microstructure. Future studies could target the role of the left retrolenticular part of the internal capsule and right superior corona radiata and the brain areas they connect.

Aerobic exercise prevents white matter microstructural degeneration in MCI adults

AbstractBackgroundWhile the use of non‐pharmacological interventions—such as physical activity, nutritional supplementation and cognitive stimulation—to prevent or delay cognitive decline and the onset of Alzheimer’s disease (AD) has received increasing attention, evidence supporting the benefits of these interventions have been mixed, and underlying mechanisms are not well‐understood.MethodIn participants enrolled in the PACE‐2 trial, which examined the impacts of 6‐month physical activity intervention on brain and cognitive outcomes, we evaluated the effects of aerobic exercise (n = 15, 63±10 yrs) on longitudinal changes in brain morphometry and white matter microstructure compared to stretching exercise controls (n = 17, 67±7 yrs.) using MRI among pre‐diabetic mild cognitive impairment adults. High‐resolution structural T1‐weighted and diffusion‐weighted images (DTI) were acquired before and after exercise intervention. Group differences in MRI markers (cortical volume and thickness, white matter DTI and free water metrics) after intervention and their longitudinal changes were compared for 68 cortical (Desikan‐Killany Atlas) and 48 white matter (JHU WM Atlas) regions using FreeSurfer SPM, FSL and Nextflow.ResultNo statistically significant group difference in cortical thickness, volumes and conventional DTI metrics was observed. On the other hand, free water (FW)‐corrected fractional anisotropy (FA) remained unchanged in aerobic exercise group (p = 0.32) while FA decreased in stretching controls in the right cerebral peduncle(p&lt;0.001), resulting in group differences in FW‐corrected FA after 6‐month exercise intervention (p = 0.02 after Bonferroni correction). These changes in stretching exercise group were negatively correlated with FW fraction changes (marker related with neuroinflammation) (r = ‐0.71, p = 0.001).ConclusionAerobic exercise could have neuroprotective effects by preventing white matter degeneration, and FW fraction and FW‐corrected imaging markers could be useful for more sensitive detection of early AD sign.

Socioeconomic differences in brain white matter microstructure and associated cognitive performance in middle to older adulthood

Socioeconomic differences in brain white matter microstructure and associated cognitive performance in middle to older adulthood

A longitudinal study identifies progressive alterations in brain white matter microstructure and networks in male adults with obstructive sleep apnea and their recovery after sleep surgery (P2-13.005)

<h3>Objective:</h3> We aimed to investigate the effects of surgical treatment on the white matter (WM) microstructure and connectivity. <h3>Background:</h3> Obstructive sleep apnea (OSA) is an increasingly prevalent clinical problem resulting in significant effects on quality of life and cognitive impairments. Surgical treatment is an effective treatment for those unable to use positive airway pressure (PAP), but the therapeutic effect of upper airway surgery on the brain has yet to be determined. <h3>Design/Methods:</h3> Twenty-one male patients with moderate to severe OSA were recruited for multi-level sleep surgery. Overnight polysomnography (PSG), neuropsychiatric tests and brain MRI scans were acquired before surgery and at least 6 months after surgery. Nineteen male patients with untreated OSA were also included as a reference group and with follow-up for 1 year or longer. We calculated the interscan changes of DTI parameters including fractional anisotropy ( FA) in the treated and untreated groups. We also assessed changes in network/connectivity properties based on graph theory. <h3>Results:</h3> Surgically treated patients showed improvement in daytime sleepiness, PSG parameters and verbal memory score after surgery. Globally FA was significantly in the surgical group compared to the untreated group; the untreated group showed disease progression (negative FA) whereas the treated group displayed no progression (near-zero FA). Especially, FA of the tracts involved in the limbic system was higher after surgery. In the analysis of network property metrics, between ness of the right cuneus and frontal pole was significantly higher and clustering coefficient of bilateral post central area was lower in the surgical group compared to the untreated group. <h3>Conclusions:</h3> Surgical treatment of OSA can prevent progressive alterations in WM microstructural integrity and disruptions in local network integration and segregation. The positive effects of surgery were prominent for the tracts involved in the limbic system, which may further explain the cognitive improvement observed after the treatment of OSA. <b>Disclosure:</b> Hea Ree Park has nothing to disclose. Dr. Chai has nothing to disclose. Dr. Joo has nothing to disclose. Prof. Kim has nothing to disclose.

Enhanced Integrity of White Matter Microstructure in Mind–Body Practitioners: A Whole-Brain Diffusion Tensor Imaging Study

Tai Chi Chuan (TCC) is an increasingly popular multimodal mind-body practice with potential cognitive benefits, yet the neurobiological mechanisms underlying these effects, particularly in relation to brain white matter (WM) microstructure, remain largely unknown. In this study, we used diffusion tensor imaging (DTI) and the attention network test (ANT) to compare 22 TCC practitioners and 18 healthy controls. We found extensive differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between the two groups. Specifically, TCC practitioners had significantly different diffusion metrics in the corticospinal tract (CST), fornix (FX)/stria terminalis (ST), and cerebral peduncle (CP). We also observed a significant correlation between increased FA values in the right CP and ANT performance in TCC practitioners. Our findings suggest that optimized regional WM microstructure may contribute to the complex information processing associated with TCC practice, providing insights for preventing cognitive decline and treating neurological disorders with cognitive impairment in clinical rehabilitation.