White Matter Microstructure Research Articles

Toward understanding the brain tissue behavior due to preconditioning: an experimental study and RVE approach.

Brain tissue under preconditioning, as a complex issue, refers to repeated loading-unloading cycles applied in mechanical testing protocols. In previous studies, only the mechanical behavior of the tissue under preconditioning was investigated; However, the link between macrostructural mechanical behavior and microstructural changes in brain tissue remains underexplored. This study aims to bridge this gap by investigating bovine brain tissue responses both before and after preconditioning. We employed a dual approach: experimental mechanical testing and computational modeling. Experimental tests were conducted to observe microstructural changes in mechanical behavior due to preconditioning, with a focus on axonal damage. Concurrently, we developed multiscale models using statistically representative volume elements (RVE) to simulate the tissue's microstructural response. These RVEs, featuring randomly distributed axonal fibers within the extracellular matrix, provide a realistic depiction of the white matter microstructure. Our findings show that preconditioning induces significant changes in the mechanical properties of brain tissue and affects axonal integrity. The RVE models successfully captured localized stresses and facilitated the microscopic analysis of axonal injury mechanisms. These results underscore the importance of considering both macro and micro scales in understanding brain tissue behavior under mechanical loading. This comprehensive approach offers valuable insights into mechanotransduction processes and improves the analysis of microstructural phenomena in brain tissue.

White matter microstructure damage measured by automated fiber quantification correlates with pain symptoms in lung cancer patients.

To investigative the white matter (WM) alterations in lung cancer patients with cancer pain (CP+), and explore the correlations between damaged WM fiber tracts and clinical indicators. Twenty-six CP+, 26 lung cancer patients without CP (CP-), and 31 healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) and clinical assessments. Automated fiber quantification (AFQ) technique was performed to identify the 20 WM fiber bundles, and the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted. Intergroup comparisons of these diffusion metrics were conducted based on the entire fiber bundle level and 100 node levels along each tract. The associations between altered diffusion metrics and the numeric rating scale (NRS) scores, as well as the pain duration, were analyzed. At the entire level, the CP + group showed impaired WM structure in the right cingulum hippocampus (CH_R). At the pointwise level, the CP + group exhibited extensive nodal FA reduction or MD, RD, and AD elevation. In addition, the AD of the posterior portion of the right inferior longitudinal fasciculus (ILF_R, nodes 71-75) in the CP + group was positively correlated with the pain duration, and the FA of CH_R (nodes 22-38) was negatively correlated with NRS score. Extensive WM microstructural damage may be a pattern of brain abnormalities in lung cancer patients with CP, and in particular, specific nodal disruption along pain-related fiber tracts may be a sensitive imaging biomarker to characterize the severity and duration of CP.

White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study

BackgroundPremenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored. MethodsDiffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton. ResultsVoxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD in several tracts. ConclusionThe main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism. Clinical trial registrationEUDRA-CT 2016–001719-19; “Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study.”; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE

Role of Microstructural White Matter Changes of Somatosensory Cortex in Stress Among Non-Clinical Population: A Diffusion Tensor Imaging Study

Introduction: Stress is a common response to stressors or potential threats, resulting in physical, affective, and cognitive changes. Emotions are linked to interpretations of bodily alterations, with the somatosensory cortex, including the postcentral gyrus, playing a key role in emotional processing. This study aimed to investigate the relationship between stress and microstructural white matter changes in the somatosensory cortex among healthy adults, crucial for early detection and treatment of stress in non-clinical populations. Materials and Methods: A total of 30 participants were recruited. The participants were administered the Depression, Anxiety, and Stress Scale 21 (DASS-21) questionnaire. All subjects underwent MRI brain scanning, with diffusion tensor imaging (DTI) used to assess white matter integrity. The association between stress scores in DASS-21 and DTI parameters was analyzed. Results: A significant negative correlation between stress scores and fractional anisotropy (FA) values in the left postcentral gyrus (r = -0.393, p = 0.32) was found, indicating early impairment by stress. No significant correlation was found in the right postcentral gyrus (r = -0.300, p = 0.107). Conclusion: Our research results demonstrated that the microstructural somatosensory cortex, especially the left postcentral gyrus, might have early changes impairment by stress using the technique of diffusion tensor imaging (DTI). Therefore, the microstructural white matter changes in the brain before suffering the disorder may be crucial and can be a novel potential biomarker for the early detection and intervention of the disease in the non-clinical population.

Development of white matter in young adulthood: The speed of brain aging and its relationship with changes in fractional anisotropy

White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.

Neuroimaging Findings From Cerebral Structure and Function in Coronary Artery Disease.

An increasing number of evidence suggests that bidirectional communication between the cardiovascular system and the central nervous system (CNS), known as the heart-brain interaction, is crucial in understanding the impact of coronary artery disease (CAD) on brain health. The multifactorial role of CAD in the brain involves processes such as inflammation, oxidative stress, neuronal activity, neuroendocrine imbalances, and reduced cerebral perfusion, leading to various cerebral abnormalities. The mechanisms underlying the relationship between CAD and brain injury are complex and involve parallel pathways in the CNS, endocrine system, and immune system. Although the exact mechanisms remain partially understood, neuroimaging techniques offer valuable insights into subtle cerebral abnormalities in CAD patients. Neuroimaging techniques, including assessment of neural function, brain metabolism, white matter microstructure, and brain volume, provide information on the evolving nature of CAD-related cerebral abnormalities over time. This review provides an overview of the pathophysiological mechanisms of CAD in the heart-brain interaction and summarizes recent neuroimaging studies utilizing multiparametric techniques to investigate brain abnormalities associated with CAD. The application of advanced neuroimaging, particularly functional, diffusion, and perfusion advanced techniques, offers high resolution, multiparametric capabilities, and high contrast, thereby allowing for the early detection of changes in brain structure and function, facilitating further exploration of the intricate relationship between CAD and brain health. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

White Matter Magnetic Resonance Diffusion Measures in Multiple Sclerosis with Overactive Bladder.

Lower urinary tract (LUT) symptoms are reported in more than 80% of patients with multiple sclerosis (MS), most commonly an overactive bladder (OAB). The relationship between brain white matter (WM) changes in MS and OAB symptoms is poorly understood. We aim to evaluate (i) microstructural WM differences across MS patients (pwMS) with OAB symptoms, patients without LUT symptoms, and healthy subjects using diffusion tensor imaging (DTI), and (ii) associations between clinical OAB symptom scores and DTI indices. Twenty-nine female pwMS [mean age (SD) 43.3 years (9.4)], including seventeen with OAB [mean age (SD) 46.1 years (8.6)] and nine without LUT symptoms [mean age (SD) 37.5 years (8.9)], and fourteen healthy controls (HCs) [mean age (SD) 48.5 years (20)] were scanned in a 3T MRI with a DTI protocol. Additionally, clinical scans were performed for WM lesion segmentation. Group differences in fractional anisotropy (FA) were evaluated using tract-based spatial statistics. The Urinary Symptom Profile questionnaire assessed OAB severity. A statistically significant reduction in FA (p = 0.004) was identified in microstructural WM in pwMS, compared with HCs. An inverse correlation was found between FA in frontal and parietal WM lobes and OAB scores (p = 0.021) in pwMS. Areas of lower FA, although this did not reach statistical significance, were found in both frontal lobes and the rest of the non-dominant hemisphere in pwMS with OAB compared with pwMS without LUT symptoms (p = 0.072). This study identified that lesions affecting different WM tracts in MS can result in OAB symptoms and demonstrated the role of the WM in the neural control of LUT functions. By using DTI, the association between OAB symptom severity and WM changes were identified, adding knowledge to the current LUT working model. As MS is predominantly a WM disease, these findings suggest that regional WM involvement, including of the anterior corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and superior frontal-occipital fasciculus and a non-dominant prevalence in WM, can result in OAB symptoms. OAB symptoms in MS correlate with anisotropy changes in different white matter tracts as demonstrated by DTI. Structural impairment in WM tracts plays an important role in LUT symptoms in MS.

Plasma biomarkers in chronic single moderate-severe traumatic brain injury.

Blood biomarkers are an emerging diagnostic and prognostic tool that reflect a range of neuropathological processes following traumatic brain injury (TBI). Their effectiveness in identifying long-term neuropathological processes after TBI is unclear. Studying biomarkers in the chronic phase is vital because elevated levels in TBI might result from distinct neuropathological mechanisms during acute and chronic phases. Here, we examine plasma biomarkers in the chronic period following TBI and their association with amyloid and tau PET, white matter microarchitecture, brain age and cognition. We recruited participants ≥40 years of age who had suffered a single moderate-severe TBI ≥10 years previously between January 2018 and March 2021. We measured plasma biomarkers using single molecule array technology [ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light (NfL), tau, glial fibrillary acidic protein (GFAP) and phosphorylated tau (P-tau181)]; PET tracers to measure amyloid-β (18F-NAV4694) and tau neurofibrillary tangles (18F-MK6240); MRI to assess white matter microstructure and brain age; and the Rey Auditory Verbal Learning Test to measure verbal-episodic memory. A total of 90 post-TBI participants (73% male; mean = 58.2 years) were recruited on average 22 years (range = 10-33 years) post-injury, and 32 non-TBI control participants (66% male; mean = 57.9 years) were recruited. Plasma UCH-L1 levels were 67% higher {exp(b) = 1.67, P = 0.018, adjusted P = 0.044, 95% confidence interval (CI) [10% to 155%], area under the curve = 0.616} and P-tau181 were 27% higher {exp(b) = 1.24, P = 0.011, adjusted P = 0.044, 95% CI [5% to 46%], area under the curve = 0.632} in TBI participants compared with controls. Amyloid and tau PET were not elevated in TBI participants. Higher concentrations of plasma P-tau181, UCH-L1, GFAP and NfL were significantly associated with worse white matter microstructure but not brain age in TBI participants. For TBI participants, poorer verbal-episodic memory was associated with higher concentration of P-tau181 {short delay: b = -2.17, SE = 1.06, P = 0.043, 95% CI [-4.28, -0.07]; long delay: bP-tau = -2.56, SE = 1.08, P = 0.020, 95% CI [-4.71, -0.41]}, tau {immediate memory: bTau = -6.22, SE = 2.47, P = 0.014, 95% CI [-11.14, -1.30]} and UCH-L1 {immediate memory: bUCH-L1 = -2.14, SE = 1.07, P = 0.048, 95% CI [-4.26, -0.01]}, but was not associated with functional outcome. Elevated plasma markers related to neuronal damage and accumulation of phosphorylated tau suggest the presence of ongoing neuropathology in the chronic phase following a single moderate-severe TBI. Plasma biomarkers were associated with measures of microstructural brain disruption on MRI and disordered cognition, further highlighting their utility as potential objective tools to monitor evolving neuropathology post-TBI.

A longitudinal MRI analysis reveals altered brain connectivity and microstructural changes in a transgenic mouse model of Alzheimer's disease

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice. In addition, significant reductions in fractional anisotropy (FA) were observed in the corpus callosum of J20 mice compared to WT, indicative of microstructural alterations consistent with white matter pathology. The observed alterations in brain connectivity and microstructure provide valuable insights into the spatiotemporal processes underlying AD-related decline and underscore the utility of multimodal neuroimaging in elucidating the neurobiological substrates of AD pathology in animal models.

Peak width of skeletonized mean diffusivity as a neuroimaging biomarker in first-episode schizophrenia.

Peak width of skeletonized mean diffusivity (PSMD), a fully automated diffusion tensor imaging (DTI) biomarker of white matter (WM) microstructure damage, has been shown to be associated with cognition in various WM pathologies. However, its application in schizophrenic disease remains unexplored. This study aims to investigate PSMD along with other DTI markers in first-episode schizophrenia patients compared to healthy controls (HCs), and explore the correlations between these metrics and clinical characteristics. A total of 56 first-episode drug-naive schizophrenia patients and 64 HCs were recruited for this study. Participants underwent structural imaging and DTI, followed by comprehensive clinical assessments, including the Positive and Negative Syndrome Scale (PANSS) for patients and cognitive function tests for all participants. We calculated PSMD, peak width of skeletonized fractional anisotropy (PSFA), axial diffusivity (PSAD), radial diffusivity (PSRD) values, skeletonized average mean diffusivity (MD), average fractional anisotropy (FA), average axial diffusivity (AD), and average radial diffusivity (RD) values as well as structural network global topological parameters, and examined between-group differences in these WM metrics. Furthermore, we investigated associations between abnormal metrics and clinical characteristics. Compared to HCs, patients exhibited significantly increased PSMD values (t = 2.467, p = 0.015), decreased global efficiency (Z = -2.188, p = 0.029), and increased normalized characteristic path length (lambda) (t = 2.270, p = 0.025). No significant differences were observed between the groups in the remaining metrics, including PSFA, PSAD, PSRD, average MD, FA, AD, RD, local efficiency, normalized cluster coefficient, small-worldness, assortativity, modularity, or hierarchy (p > 0.05). After adjusting for relevant variables, both PSMD and lambda values exhibited a significant negative correlation with reasoning and problem-solving scores (PSMD: r = -0.409, p = 0.038; lambda: r = -0.520, p = 0.006). No statistically significant correlations were observed between each PANSS score and the aforementioned metrics in the patient group (p > 0.05). Multivariate linear regression analysis revealed that increased PSMD (β = -0.426, t = -2.260, p = 0.034) and increased lambda (β = -0.490, t = -2.994, p = 0.007) were independently associated with decreased reasoning and problem-solving scores respectively ( = 0.295, F = 2.951, p = 0.029). But these significant correlations did not withstand FDR correction (p_FDR > 0.05). PSMD can be considered as a valuable neuroimaging biomarker that complements conventional diffusion measurements for investigating abnormalities in WM microstructural integrity and cognitive functions in schizophrenia.

Assessing Visual Pathway White Matter Degeneration in Primary Open‐Angle Glaucoma Using Multiple MRI Morphology and Diffusion Metrics

BackgroundPrimary open‐angle glaucoma (POAG), a leading cause of irreversible blindness, is associated with neurodegeneration in the visual pathway, but the underlying pathophysiology remains incompletely resolved.PurposeTo characterize macro‐ and microstructural white matter abnormalities in optic tract (OT) and optic radiation (OR) of POAG.Study typeProspective.PopulationsA total of 34 POAG patients (21 males, 13 females) and 25 healthy controls (HCs) (16 males, nine females).Field Strength/Sequence3 T; multiband spin‐echo echo planar diffusion spectrum imaging (DSI).AssessmentWe compared multiple morphology metrics, including volume, area, length, and shape metrics, as well as diffusion metrics such as diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity, radial diffusivity, and axial diffusivity), mean apparent propagator (mean squared displacement, q‐space inverse variance, return‐to‐origin probability, return‐to‐axis probabilities [RTAP] and return‐to‐plane probabilities, non‐Gaussianity, perpendicular non‐Gaussianity, parallel non‐Gaussianity), and neurite orientation dispersion and density imaging (intracellular volume fraction, orientation dispersion index [ODI], and isotropic volume fraction of the OT and OR).Statistical TestsStatistical comparisons and classifications employed linear mixed model and logistic regression. Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). P‐value <0.05 was statistically significant.ResultsMorphology analysis in POAG revealed a lower span in the OR (29.43 ± 2.30 vs. 30.59 ± 2.01, 3.8%) and OT (19.73 ± 2.21 vs. 20.68 ± 1.37, 4.6%), and a higher curl (3.03 ± 0.22 vs. 2.90 ± 0.16, 4.5%) in OT. Diffusion metrics revealed lower mean FA (OR: 0.328 ± 0.03 vs. 0.340 ± 0.018, 3.5%; OT: 0.255 ± 0.022 vs. 0.268 ± 0.018, 4.9%) and lower mean RTAP (OR: 5.919 ± 0.529 vs. 6.216 ± 0.489, 4.8%; OT: 4.089 ± 0.402 vs. 4.280 ± 0.353, 4.5%), with higher mean ODI in the OT (0.448 ± 0.029 vs. 0.433 ± 0.025, 3.5%). Combined models, incorporating these MRI metrics, effectively discriminated POAG from HCs, achieving AUCs of 0.84 for OR and 0.83 for OT.Data ConclusionsDSI‐derived morphology and diffusion metrics demonstrated macro‐ and micro abnormalities in the visual pathway, providing insights into POAG‐related neurodegeneration.Level of Evidence2Technical EfficacyStage 3

White matter microstructural and inflammation-based subgroups in bipolar disorder II depression differentiate in depressive and psychotic symptoms

BackgroundElevated inflammation and impaired white matter (WM) microstructure have been observed in bipolar disorder (BD). The link between inflammation, WM integrity, and psychiatric symptoms in BD-II depression (BDII-D) remains unknown. We aimed to define BDII-D subgroups through the interplay of inflammation and WM microstructure, and to explore differences in psychiatric symptoms between subgroups, thus offering insight into elucidating the explanatory measures linked to BDII-D. MethodsWM differences were compared between 146 BDII-D individuals and 151 health controls (HCs) by Tract-Based Spatial Statistics. Partial correlation with multiple comparison corrections was used to explore associations between WM, inflammation, and psychiatric symptoms. The canonical correlation analysis metrics of WM and inflammation followed by k-means clustering were used to define WM microstructural-inflammation subgroups of BDII-D. The differences in clinical profiles were compared between the subgroups. ResultsCompared with HCs, BDII-D showed significant WM alterations in the anterior thalamic radiation (ATR), cingulum, forceps, and inferior fronto-occipital fasciculus. In BDII-D, lower fraction anisotropy (FA) within the right ATR and cingulum were significantly associated with higher interleukin-6, while lower FA in the cingulum and lower axial diffusivity in the forceps major exhibited significant links with higher C-reactive protein. Among the subgroups identified, subgroup II characterized by elevated inflammation and impaired WM integrity displayed greater psychiatric symptoms. ConclusionsWM alterations are concentrated in emotional neurocircuits and are linked to inflammation in BDII-D. WM-inflammation subgroups exhibit distinct variations in psychiatric symptoms. Thus, WM alterations and inflammation might be an explanatory process in the pathophysiology of BDII-D.

Neurite Orientation Dispersion and Density Imaging (NODDI) reveals white matter microstructural changes in Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) patients with cognitive impairment

PurposeThis study aimed to assess changes in white matter microstructure among patients undergoing obstructive sleep apnea hypopnea syndrome (OSAHS) complicated by cognitive impairment through neurite orientation dispersion and density imaging (NODDI), and evaluate the relationship to cognitive impairment as well as the diagnostic performance in early intervention. MethodsTotally 23 OSAHS patients, 43 OSAHS patients complicated by cognitive impairment, and 15 healthy controls were enrolled in OSA, OSACI and HC groups of this work. NODDI toolbox and FMRIB's Software Library (FSL) were used to calculate neurite density index (NDI), Fractional anisotropy (FA), volume fraction of isotropic water molecules (Viso), and orientation dispersion index (ODI). Tract-based spatial statistics (TBSS) were carried out to examine the above metrics with one-way ANOVA. This study explored the correlations of the above metrics with mini-mental state examination (MMSE), and montreal cognitive assessment (MoCA) scores. Furthermore, receiver operating characteristic (ROC) curves were plotted. Meanwhile, area under curve (AUC) values were calculated to evaluate the diagnostic performance of the above metrics. ResultsNDI, ODI, Viso, and FA were significantly different among different brain white matter regions, among which, difference in NDI showed the greatest statistical significance. In comparison with HC group, OSA group had reduced NDI and ODI, whereas elevated Viso levels. Conversely, compared to the OSA group, the OSACI group displayed a slight increase in NDI and ODI values, which remained lower than HC group, viso values continued to rise. Post-hoc analysis highlighted significant differences in these metrics, except for FA, which showed no notable changes or correlations with neuropsychological tests. ROC analysis confirmed the diagnostic efficacy of NDI, ODI, and Viso with AUCs of 0.6908, 0.6626, and 0.6363, respectively, whereas FA's AUC of 0.5042, indicating insufficient diagnostic efficacy. ConclusionsThis study confirmed that NODDI effectively reveals microstructural changes in white matter of OSAHS patients with cognitive impairment, providing neuroimaging evidence for early clinical diagnosis and intervention.

B - 55 Diffusion Tensor Imaging Analysis of Former American Football Players Exposed to Repetitive Head Impacts

Abstract Objective Exposure to repetitive head impacts (RHI) has been linked to Chronic Traumatic Encephalopathy (CTE) and neuropathological alterations such as white matter shear injuries. In this study, we use diffusion-tensor imaging (DTI) to investigate in vivo white matter alterations among former American football players. We also investigate how age and factors associated with RHI exposure influence white matter integrity. Methods We analyzed data from the DIAGNOSE CTE Research Project, focusing on former American football players (n = 166). The measures included whole-brain Fractional Anisotropy (FA), reflecting water diffusion directionality in white matter, and FreeWater-corrected FA (FAt) accounting for extracellular free water, using FSL Tract-Based Spatial Statistics (TBSS). We performed linear regressions on FA and FAt with age, age of first exposure to football, and estimates of cumulative head impact index (CHII) scores of frequency, linear acceleration, and rotational force controlling for age, body mass index, race, education, and APOE e4 allele presence as covariates. Results Both FA (p < 0.00001) and FAt (p < 0.00001) decreased as age increased. Moreover, FA (p < 0.01) and FAt (p < 0.01) were significantly lower with an earlier age of first exposure to football. Finally, FAt decreased as CHII linear acceleration (p < 0.04) and rotational forces (p < 0.02) increased. Conclusion Our study reveals age-related declines in both FA and FAt and highlights that the duration and intensity of exposure to RHI have an impact on white matter microstructure later in life. Overall, these results underscore the impact of prolonged exposure to RHI on white matter microstructure.

White Matter Microstructure Changes Revealed by Diffusion Kurtosis and Diffusion Tensor Imaging in Mutant Huntingtin Gene Carriers.

Diffusion magnetic resonance imaging (dMRI) has revealed microstructural changes in white matter (WM) in Huntington's disease (HD). To compare the validities of different dMRI, i.e., diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in HD. 22 mutant huntingtin (mHTT) carriers and 14 controls were enrolled. Clinical assessments and dMRI were conducted. Based on CAG-Age Product (CAP) score, mHTT carriers were categorized into high CAP (hCAP) and medium and low CAP (m& lCAP) groups. Spearman analyses were used to explore correlations between imaging parameters in brain regions and clinical assessments. Receiver operating characteristic (ROC) was used to distinguish mHTT carriers from control, and define the HD patients at advanced stage. Compared to controls, mHTT carriers exhibited WM changes in DKI and DTI. There were 22 more regions showing significant differences in HD detected by MK than FA. Only MK in five brain regions showed significantly difference between any two group, and negatively correlated with the disease burden (r = -0.80 to -0.71). ROC analysis revealed that MK was more sensitive and FA was more specific, while Youden index showed that the integration of FA and MK gave rise to higher authenticities, in distinguishing m& lCAP from controls (Youden Index = 0.786), and discerning different phase of HD (Youden Index = 0.804). Microstructural changes in WM occur at early stage of HD and deteriorate over the disease progression. Integrating DKI and DTI would provide the best accuracies for differentiating early HD from control and identifying advanced HD.

Long-term brain structural and cognitive outcomes in a low-risk preterm-born sample

Prematurity has been related to altered brain structure and cognition, and so our aim was to describe them in the absence of major structural brain injury following low-risk preterm birth during adolescence and young adulthood. The sample consisted of 250 participants, 132 of whom were low-risk preterm (30–36 weeks’ gestational age) and 118 were full-term individuals (37–42 weeks’ gestational age), aged between 16 and 38 years old. All participants underwent an extensive neuropsychological assessment. T1- and diffusion-weighted MRI images of 33 low-risk preterm and 31 full-term young adults (20–32 years old) were analyzed. No differences were found in terms of general cognitive functioning score or current socioeconomic status; however, the low-risk preterm group obtained lower scores in phonetic and semantic fluencies, and theory of mind. Significant reductions were identified in the thalamus volume as well as thicker cortex in the inferior temporal gyrus in the low-risk preterm group. Low-risk preterm young adults evidenced greater regional AD and MD compared to the full-term sample; while low-risk preterm group showed lower mean NDI and ODI (FWE-corrected, p < 0.05). Being born preterm is associated with poorer performance in various cognitive domains (i.e., phonetic and semantic fluencies, and theory of mind) later in life, along with differences in normative structural brain development in inferior temporal gyrus and regional white matter microstructure.

Tractography of sensorimotor pathways in dyskinetic cerebral palsy: Association with motor function.

Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico-striatal-thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP. Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS). White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways. The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well-described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes.

Cognitive processing speed and accuracy are intrinsically different in genetic architecture and brain phenotypes

Since the birth of cognitive science, researchers have used reaction time and accuracy to measure cognitive ability. Although recognition of these two measures is often based on empirical observations, the underlying consensus is that most cognitive behaviors may be along two fundamental dimensions: cognitive processing speed (CPS) and cognitive processing accuracy (CPA). In this study, we used genomic-wide association studies (GWAS) data from 14 cognitive traits to show the presence of those two factors and revealed the specific neurobiological basis underlying them. We identified that CPS and CPA had distinct brain phenotypes (e.g. white matter microstructure), neurobiological bases (e.g. postsynaptic membrane), and developmental periods (i.e. late infancy). Moreover, those two factors showed differential associations with other health-related traits such as screen exposure and sleep status, and a significant causal relationship with psychiatric disorders such as major depressive disorder and schizophrenia. Utilizing an independent cohort from the Adolescent Brain Cognitive Development (ABCD) study, we also uncovered the distinct contributions of those two factors on the cognitive development of young adolescents. These findings reveal two fundamental factors underlying various cognitive abilities, elucidate the distinct brain structural fingerprint and genetic architecture of CPS and CPA, and hint at the complex interrelationship between cognitive ability, lifestyle, and mental health.

Identification of genetic basis of brain imaging by group sparse multi-task learning leveraging summary statistics

Brain imaging genetics is an evolving neuroscience topic aiming to identify genetic variations related to neuroimaging measurements of interest. Traditional linear regression methods have shown success, but their reliance on individual-level imaging and genetic data limits their applicability. Herein, we proposed S-GsMTLR, a group sparse multi-task linear regression method designed to harness summary statistics from genome-wide association studies (GWAS) of neuroimaging quantitative traits. S-GsMTLR directly employs GWAS summary statistics, bypassing the requirement for raw imaging genetic data, and applies multivariate multi-task sparse learning to these univariate GWAS results. It amalgamates the strengths of conventional sparse learning methods, including sophisticated modeling techniques and efficient feature selection. Additionally, we implemented a rapid optimization strategy to alleviate computational burdens by identifying genetic variants associated with phenotypes of interest across the entire chromosome. We first evaluated S-GsMTLR using summary statistics derived from the Alzheimer's Disease Neuroimaging Initiative. The results were remarkably encouraging, demonstrating its comparability to conventional methods in modeling and identification of risk loci. Furthermore, our method was evaluated with two additional GWAS summary statistics datasets: One focused on white matter microstructures and the other on whole brain imaging phenotypes, where the original individual-level data was unavailable. The results not only highlighted S-GsMTLR's ability to pinpoint significant loci but also revealed intriguing structures within genetic variations and loci that went unnoticed by GWAS. These findings suggest that S-GsMTLR is a promising multivariate sparse learning method in brain imaging genetics. It eliminates the need for original individual-level imaging and genetic data while demonstrating commendable modeling and feature selection capabilities.

White matter microstructure and functional connectivity in the brains of infants with Turner syndrome.

Turner syndrome, caused by complete or partial loss of an X-chromosome, is often accompanied by specific cognitive challenges. Magnetic resonance imaging studies of adults and children with Turner syndrome suggest these deficits reflect differences in anatomical and functional connectivity. However, no imaging studies have explored connectivity in infants with Turner syndrome. Consequently, it is unclear when in development connectivity differences emerge. To address this gap, we compared functional connectivity and white matter microstructure of 1-year-old infants with Turner syndrome to typically developing 1-year-old boys and girls. We examined functional connectivity between the right precentral gyrus and five regions that show reduced volume in 1-year old infants with Turner syndrome compared to controls and found no differences. However, exploratory analyses suggested infants with Turner syndrome have altered connectivity between right supramarginal gyrus and left insula and right putamen. To assess anatomical connectivity, we examined diffusivity indices along the superior longitudinal fasciculus and found no differences. However, an exploratory analysis of 46 additional white matter tracts revealed significant group differences in nine tracts. Results suggest that the first year of life is a window in which interventions might prevent connectivity differences observed at later ages, and by extension, some of the cognitive challenges associated with Turner syndrome.