White Matter Alterations Research Articles

778 Poor Sleep Quality is Associated with Reduced Myelination in Patients with Psychotic Disorders

Abstract Introduction Recent studies show that sleep favors oligodendrocyte proliferation and myelination, and sleep loss is associated with alterations in white matter structure and decreased myelination. Psychotic disorders are characterized by disrupted white matter integrity, and abnormal axon and myelin structure. Despite common sleep disturbances in these disorders, little is known about the relationship between sleep quality and white matter findings. A novel in vivo neuroimaging technique that combines diffusion tensor spectroscopy (DTS) and magnetization transfer ratio (MTR) allows separately examining the axon structure and glial function, and myelin content, respectively. Using this method, we examined the association of sleep quality with white matter biology in a sample of patients with psychotic disorders and matched healthy controls. Methods Participants included patients diagnosed with bipolar disorder with psychotic features (euthymic or depressed, n=12) and schizophrenia spectrum disorders (n=9), and age and sex matched healthy controls (n=20). DTS and MTR data was collected from the right prefrontal white matter at 4T. DTS measures included apparent diffusion coefficients of water, NAA, creatine and choline. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI). Results PSQI total score was significantly higher in patients. and patient sample included a higher percentage of poor sleepers (PSQI total score>5). In patients, total PSQI score and sleep onset latency were significantly and negatively associated with MTR (F=6.9, p=0.02 and F=9.7, p=0.007, respectively). There was no difference in any DTS measures between groups. Conclusion Our preliminary results show that poor sleep quality is associated with decreased myelin content in the frontal lobe, in patients with psychotic disorders. This finding suggests that sleep loss may be a mediator of white matter alterations in psychosis. Support (if any) This work is supported by National Institute of Mental Health K23MH119322 to Cagri Yuksel

Altered White Matter Microstructures in Type 2 Diabetes Mellitus: A Coordinate-Based Meta-Analysis of Diffusion Tensor Imaging Studies.

ObjectiveType 2 diabetes mellitus (T2DM) is often accompanied by cognitive decline and depressive symptoms. Numerous diffusion tensor imaging (DTI) studies revealed microstructural white matter (WM) abnormalities in T2DM but the findings were inconsistent. The present study aimed to conduct a coordinate‐based meta‐analysis (CBMA) to identify statistical consensus of DTI studies in T2DM.MethodsWe performed a systematic search on relevant studies that reported fractional anisotropy (FA) differences between T2DM patients and healthy controls (HC). The anisotropic effect size seed‐based d mapping (AES-SDM) approach was used to explore WM alterations in T2DM. A meta‐regression was then used to analyze potential influences of sample characteristics on regional FA changes.ResultsA total of eight studies that comprised 245 patients and 200 HC, along with 52 coordinates were extracted. The meta‐analysis identified FA reductions in three clusters including the left inferior network, the corpus callosum (CC), and the left olfactory cortex. Besides, FA in the CC was negatively correlated with body mass index (BMI) in the patients group.ConclusionsT2DM could lead to subtle WM microstructural alterations, which might be associated with cognitive deficits or emotional distress symptoms. This provides a better understanding of the pathophysiology of neurodegeneration and complications in T2DM.Systematic Review RegistrationRegistered at PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42020218737.

Probing white matter microstructure in youth with chronic pain

Alterations in white matter (WM) have been reported in individuals with chronic pain, although findings are inconsistent, and mostly derived using the limited Diffusion Tensor Imaging (DTI) model. Going beyond DTI, one study reported lower WM complexity in corpus callosum, internal capsule and a hippocampus tract. In youth with chronic pain, no studies have examined WM changes, except in headache. The current study therefore examined potential WM alterations in youth with chronic pain using DTI as well as Neurite Orientation Dispersion and Density Imaging (NODDI), allowing more specific interrogation of WM microstructure. Multi-shell diffusion-weighted MR images were analyzed in 45 youth with chronic pain (age M=15.8±2.5, 41 females) and 25 controls (age M=16.0±3.2, 18 females). Preprocessing included estimation and correction of susceptibility-, eddy current-, and motion-induced distortions (FSL). DTI and NODDI models were fit, deriving indices of fractional anisotropy (FA/DTI), neurite density (NDI/NODDI) and orientation dispersion (ODI/NODDI). Data was spatially aligned using tensor-based alignment (DTI-TK), followed by tract-based spatial statistics (TBSS; TFCE-corrected). Group contrasts showed that while there were no group differences in FA and NDI, patients showed increased ODI in several tracts, including the corticospinal tract, corpus callosum and forceps minor (connecting medial and lateral frontal lobe), uncinate fasciculus (connecting frontal and temporal lobe), internal capsule (connecting subcortical structures) and fornix (a hippocampus tract). Our findings reveal specific WM alterations in several tracts that are implicated in (chronic) pain. In particular, the dispersion in fiber orientation was increased, reflective of less coherently organized fibers. This may indicate possible delayed pruning in these tracts. Neurite density indices were not different, reflective of similar amounts of fibers and myelin. Taken together, youth with chronic pain showed specific alterations in fiber dispersion of several WM tracts in cortico-limbic circuitry. Future work will examine associations with individual difference factors. NIH R01HD083270 to LE Simons.

White matter analysis of the extremely preterm born adult brain

The preterm brain has been analysed after birth by a large body of neuroimaging studies; however, few studies have focused on white matter alterations in preterm subjects beyond infancy, especially in individuals born at extremely low gestation age - before 28 completed weeks. Neuroimaging data of extremely preterm young adults are now available to investigate the long-term structural alterations of disrupted neurodevelopment. We examined white matter hierarchical organisation and microstructure in extremely preterm young adults. Specifically, we first identified the putative hubs and peripheral regions in 85 extremely preterm young adults and compared them with 53 socio-economically matched and full-term born peers. Moreover, we analysed Fractional Anisotropy (FA), Mean Diffusivity (MD), Neurite Density Index (NDI), and Orientation Dispersion Index (ODI) of white matter in hubs, peripheral regions, and over the whole brain. Our results suggest that the hierarchical organisation of the extremely preterm adult brain remains intact. However, there is evidence of significant alteration of white matter connectivity at both the macro- and microstructural level, with overall diminished connectivity, reduced FA and NDI, increased MD, and comparable ODI; suggesting that, although the spatial configuration of WM fibres is comparable, there are less WM fibres per voxel. These alterations are found throughout the brain and are more prevalent along the pathways between deep grey matter regions, frontal regions and cerebellum. This work provides evidence that white matter abnormalities associated with the premature exposure to the extrauterine environment not only are present at term equivalent age but persist into early adulthood.

Functional Hyper Connectivity Between Cerebro Cerebellar Networks and Altered Decision Making in Young Adult Cannabis Users: Evidence From 7T and Multivariate Pattern Analysis

Deficits in decision-making (DM) are an important predictor of cannabis use and relapse rates. Cannabis use is associated with disrupted brain network dynamics between the cerebro-cerebellum. Unified multimodal methods [Resting state connectivity, Diffusion Tensor Imaging (DTI) and cortical thickness (CT) analyses] were employed to test the hypothesis that cannabis users (CU) have deficits in DM and these deficits may be due to alterations in white matter (WM) connectivity, functional connectivity, and cortical thickness (CT).

White matter alterations in young children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can lead to cognitive, behavioural, and social-emotional challenges. Previous neuroimaging research has identified structural brain alterations in newborns, older children, adolescents, and adults with PAE; however, little is known about brain structure in young children. Extensive brain development occurs during early childhood; therefore, understanding the neurological profiles of young children with PAE is critical for early identification and effective intervention. We studied 54 children (5.21±1.11years; 27 males) with confirmed PAE (94% also had other prenatal exposures, 74% had adverse postnatal experiences) compared with 54 age- and sex-matched children without PAE. Children underwent diffusion tensor imaging between 2 and 7years of age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major white matter tracts. Univariate analyses of covariance were used to test group differences (PAE vs. control) controlling for age and sex. The PAE group had higher FA in the genu of the corpus callosum and lower MD in the bilateral uncinate fasciculus. The PAE group also had lower tract volume in the corpus callosum, the bilateral inferior fronto-occipital fasciculi, and the right superior longitudinal fasciculus. Our findings align with studies of newborns with PAE reporting lower diffusivity, but contrast those in older populations with PAE, which consistently report lower FA and higher MD. Further research is needed to understand trajectories of white matter development and how our results of higher FA/lower MD in young children connect with lower FA/higher MD observed at older ages.

Obsessive Compulsive Symptom Dimensions are Linked to Altered White Matter Microstructure in a Community Sample of Adolescents

Population-based studies demonstrate a continuum between subclinical OCD symptoms (OCS) and clinically severe OCD in school-aged samples, highlighting the potential for neuroimaging studies to detect markers of severity across the disorder continuum. Recent evidence suggests that white matter alterations previously attributed to specific psychopathologies are in fact shared across major diagnostic boundaries. This situation indicates a critical need to model OCD psychopathology in a hierarchical and multidimensional framework that accounts for the transdiagnostic features of psychopathology risk.

Microstructural white matter alterations in Alzheimer's disease and amnestic mild cognitive impairment and its diagnostic value based on diffusion kurtosis imaging: a tract-based spatial statistics study.

This prospective study aimed to explore the white matter microstructural alterations in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using the Tract-based Spatial Statistics (TBSS) method of diffusion kurtosis imaging (DKI).Diffusion images were collected from 45AD patients, 42 aMCI patients, and 35 healthy controls (HC). The differences of DKI-derived parameters, including kurtosis fractional anisotropy (KFA), mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD), were compared across the three groups using the TBSS method. Correlation between the altered DKI-derived parameters and the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were analyzed. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of different white matter parameters with the strongest correlations. As a result, compared with the HC group, KFA values decreased significantly in the aMCI group. Compared with both the HC and aMCI groups, the FA, KFA, and MK values decreased significantly and the MD value increased significantly in the AD group. FA, MD, KFA, and MK values of many white matter fiber tracts were significantly correlated with MMSE and MoCA scores. The area under the ROC curve (AUC) for the splenium of corpus callosum KFA values were highest for the diagnosis of aMCI and AD patients. In conclusion, the compactness and complexity of white matter microstructures were reduced in AD and aMCI patients. DKI can provide information about the severity of AD progression, and KFA might be more sensitive for the detection of white matter microstructural alterations.

Exploring Variances of White Matter Integrity and the Glymphatic System in Simple Febrile Seizures and Epilepsy.

Background: Simple febrile seizures (SFS) and epilepsy are common seizures in childhood. However, the mechanism underlying SFS is uncertain, and the presence of obvious variances in white matter (WM) integrity and glymphatic function between SFS and epilepsy remain unclear. Therefore, this study aimed to investigate the differences in WM integrity and glymphatic function between SFS and epilepsy.Material and Methods: We retrospectively included 26 children with SFS, 33 children with epilepsy, and 28 controls aged 6–60 months who underwent magnetic resonance imaging (MRI). Tract-based spatial statistics (TBSS) were used to compare the diffusion tensor imaging (DTI) metrics of WM among the above-mentioned groups. T2-weighted imaging (T2WI) was used to segment the visible Virchow-Robin space (VRS) through a custom-designed automated method. VRS counts and volume were quantified and compared among the SFS, epilepsy, and control groups. Correlations of the VRS metrics and seizure duration and VRS metrics and the time interval between seizure onset and MRI scan were also investigated.Results: In comparison with controls, children with SFS showed no significant changes in fractional anisotropy (FA), axial diffusivity (AD), or radial diffusivity (RD) in the WM (P > 0.05). Decreased FA, unchanged AD, and increased RD were observed in the epilepsy group in comparison with the SFS and control groups (P < 0.05). Meanwhile, VRS counts were higher in the SFS and epilepsy groups than in the control group (VRS_SFS, 442.42 ± 74.58, VRS_epilepsy, 629.94 ± 106.55, VRS_control, 354.14 ± 106.58; P < 0.001), and similar results were found for VRS volume (VRS_SFS, 6,228.18 ± 570.74 mm3, VRS_epilepsy, 9,684.84 ± 7,292.66mm3, VRS_control, 4,007.22 ± 118.86 mm3; P < 0.001). However, VRS metrics were lower in the SFS group than in the epilepsy group (P < 0.001). In both SFS and epilepsy, VRS metrics positively correlated with seizure duration and negatively correlated with the course after seizure onset.Conclusion: SFS may not be associated with WM microstructural disruption; however, epilepsy is related to WM alterations. Seizures are associated with glymphatic dysfunction in either SFS or epilepsy.

Leukoencephalopathy with transient splenial lesions related to 5-fluorouracil or capecitabine.

5-Fluorouracil (5-FU) and its oral prodrug capecitabine have been rarely but consistently associated with acute central nervous system toxicity, including transient leukoencephalopathies involving the splenium of the corpus callosum. We performed a retrospective search in the French Pharmacovigilance database (FPDB) (January 1985-July 2020) for adult patients affected by solid cancers who developed acute toxic leukoencephalopathies with splenial lesions following treatment with 5-FU or capecitabine. A comprehensive review of the literature helped to circumstantiate our findings. Our research in the FPDB identified six patients who, within 3days from their first cycle of 5-FU or capecitabine, developed acute neurological symptoms, including gait ataxia (n=4), dysarthria (n=3), dysmetria (n=2), headache (n=2), and confusion (n=2). Brain magnetic resonance imaging (MRI) showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities in the corpus callosum, with diffusion restriction and no contrast enhancement, generally accompanied by additional alterations in the bilateral supratentorial white matter (n=5). All patients discontinued the agent supposedly responsible for the toxicity and experienced full recovery after a median of 8.5days from symptom onset. Control MRI showed a progressive normalization of acute MRI abnormalities. Literature review identified 26 cases with similar clinical and paraclinical characteristics. A single patient from the literature resumed 5-FU at a lower dose, with no recurrent toxicity. 5-FU and capecitabine might be responsible for acute leukoencephalopathies with transient splenial lesions that are generally reversible upon drug discontinuation. Resuming the agent responsible for toxicity might be feasible in selected cases, after having excluded dihydropyrimidine dehydrogenase deficiency, if expected benefits outweigh the risks.

A unified model of the pathophysiology of bipolar disorder.

This work provides an overview of the most consistent alterations in bipolar disorder (BD), attempting to unify them in an internally coherent working model of the pathophysiology of BD. Data on immune-inflammatory changes, structural brain abnormalities (in gray and white matter), and functional brain alterations (from neurotransmitter signaling to intrinsic brain activity) in BD were reviewed. Based on the reported data, (1) we hypothesized that the core pathological alteration in BD is a damage of the limbic network that results in alterations of neurotransmitter signaling. Although heterogeneous conditions can lead to such damage, we supposed that the main pathophysiological mechanism is traceable to an immune/inflammatory-mediated alteration of white matter involving the limbic network connections, which destabilizes the neurotransmitter signaling, such as dopamine and serotonin signaling. Then, (2) we suggested that changes in such neurotransmitter signaling (potentially triggered by heterogeneous stressors onto a structurally-damaged limbic network) lead to phasic (and often recurrent) reconfigurations of intrinsic brain activity, from abnormal subcortical-cortical coupling to changes in network activity. We suggested that the resulting dysbalance between networks, such as sensorimotor networks, salience network, and default-mode network, clinically manifest in combined alterations of psychomotricity, affectivity, and thought during the manic and depressive phases of BD. Finally, (3) we supposed that an additional contribution of gray matter alterations and related cognitive deterioration characterize a clinical-biological subgroup of BD. This model may provide a general framework for integrating the current data on BD and suggests novel specific hypotheses, prompting for a better understanding of the pathophysiology of BD.

Late-life cynical hostility is associated with white matter alterations and the risk of Alzheimer's disease.

Cynical hostility (CH), a specific dimension of hostility that consists of a mistrust of others, has been suggested as a high-risk trait for dementia. However, the influence of CH on the incidence of Alzheimer's disease (AD) remains poorly understood. This study investigated whether late-life CH is associated with AD risk and structural neuroimaging markers of AD. In community-dwelling older adults from the French ESPRIT cohort (n = 1388), incident dementia rate according to CH level was monitored during an 8-year follow-up and analyzed using Cox proportional hazards regression models. Brain magnetic resonance imaging volumes were measured at baseline (n = 508). Using automated segmentation procedures (Freesurfer 6.0), the authors assessed brain grey and white volumes on all magnetic resonance imaging scans. They also measured white matter hyperintensities volumes using semi-automated procedures. Mean volumes according to the level of CH were compared using ANOVA. Eighty-four participants developed dementia (32 with AD). After controlling for potential confounders, high CH was predictive of AD (HR 2.74; 95% CI 1.10-6.85; p = 0.030) and all dementia types are taken together (HR 2.30; 95% CI 1.10-4.80; p = 0.027). High CH was associated with white matter alterations, particularly smaller anterior corpus callosum volume (p < 0.01) after False Discovery Rate correction, but not with grey matter volumes. High CH in late life is associated with cerebral white matter alterations, designated as early markers of dementia, and higher AD risk. Identifying lifestyle and biological determinants related to CH could provide clues on AD physiopathology and avenues for prevention strategies.

Grey and white matter alteration in euthymic children with bipolar disorder: a combined source-based morphometry (SBM) and voxel-based morphometry (VBM) study.

Bipolar disorder (BPD) is a psychiatric condition driving frequent mood swings between periodic extremes of happiness and depression in patients. In this study, a source-based morphometry (SBM) and voxel-based morphometry (VBM) analysis was utilized to measure the differences in the white matter (WM) and grey matter (GM) between euthymic children with BPD and typically developing (TD) children. We adapted both multivariate (SBM) and univariate (VBM) analysis in 20 children with BPD euthymia /remission and compared to the same number of TD age-matched children. The VBM did not reveal any increase in GM and WM voxel values in children with BPD. However, a decrease in the GM voxel values in the bilateral middle frontal and WM voxels in the left hippocampus, left caudate, left orbitofrontal and right inferior parietal cortices was identified. Conversely, SBM analysis in BPD displayed a high GM value in bilateral angular gyrus, bilateral inferior temporal, left supplementary motor area and left middle temporal region, while a low value was observed in left inferior and middle occipital, cerebellum, thalamus, left premotor area and left lingual gyrus. These findings suggested a crucial GM and WM alteration in multiple neural regions in BPD children even during sustained and substantial remission.

Standard radiotherapy for patients with nasopharyngeal carcinoma results in progressive tract-specific brain white matter alterations: A one-year follow-up via diffusion tensor imaging

Background and purposeRadiation therapy (RT)-induced neurocognitive disability may be mediated by brain tissue damage. The aim of the present study was to investigate the effects of standard RT on normal brain tissue via in vivo neuroimaging in patients with nasopharyngeal carcinoma (NPC). Materials and methodsA total of 146 newly diagnosed NPC patients who were treated with standard RT were longitudinally followed up at multiple time points during the first year post-RT, with 19 comparable healthy controls followed up in parallel serving as normal age-related benchmarks. Magnetic resonance diffusion tensor imaging was used to evaluate longitudinal brain white matter tract changes in NPC patients. The relationships between RT-related white matter changes, hippocampal atrophy, and cognitive impairment were also assessed. ResultsBilateral cingulate angular bundle (CAB) fibers had progressive diffusion reduction [radial diffusivity (RD) and mean diffusivity] over time (P < 0.05, corrected for multiple comparisons) in NPC patients during the first year after RT. RT-associated progressive RD reduction in the left CAB correlated with longitudinal atrophy of the ipsilateral hippocampus (P = 0.033). Additionally, RT-associated progressive RD reduction in the left CAB correlated with progressive cognitive impairment in NPC patients post-RT (P = 0.048). ConclusionWe present evidence of progressive RT-associated changes in the bilateral CAB in NPC patients, which may underlie RT-related cognitive impairment. These findings illustrate that the use of white matter tract alterations as potential biomarkers to detect RT-related brain injury in NPC patients may be useful for better understanding the pathogenesis of RT-induced cognitive decline.

Lateralization effects in brain white matter reorganization in patients with unilateral idiopathic tinnitus: a preliminary study.

Idiopathic tinnitus can cause significant auditory-related brain structural and functional changes in patients. However, changes in patterns of the lateralization effects in idiopathic tinnitus have yet to be established, especially on white matter (WM) reorganization. In this study, we studied 19 left-sided and 19 right-sided idiopathic tinnitus (LSIT, RSIT) patients and 19 healthy controls (HCs). We combined applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses to investigate altered features of the auditory-related brain WM. We also conducted correlation analyses between the clinical variables and WM changes in the patients. Compared with the HCs, both sided tinnitus patients showed significant auditory-related brain WM alterations. More interestingly, the LSIT patients demonstrated a greater decrease in white matter volume (WMV) in the right medial superior frontal gyrus (SFG) than the RSIT; meanwhile, we also found that compared with the RSIT group, the LSIT group showed significantly increased fractional anisotropy (FA) in the body of the corpus callosum (CC), left cingulum, and right superior longitudinal fasciculus (SLF) and decreased mean diffusivity (MD) in the body of CC. Moreover, relative to the RSIT group, the LSIT group also exhibited increases in WM axial diffusivity (AD) in the left SLF, left cingulum, right middle cerebellar peduncle (MCP), left thalamus, and bilateral forceps major (FM) and decreases in radial diffusivity (RD) in the genu of CC. Additionally, the FA value of the right SLF was closely associated with tinnitus severity in the LSIT. Our study suggests that lateralization has a significant effect on WM reorganization in patients with idiopathic tinnitus; in particular, LSIT patients may experience more severe and widespread alterations in WMV and WM microstructure than the RSIT group, and all these changes are indirectly auditory related. These findings provide new useful information that can lead to a better understanding of the tinnitus mechanisms.

Age-Related Differences in White Matter: Understanding Tensor-Based Results Using Fixel-Based Analysis.

Aging is associated with widespread alterations in cerebral white matter (WM). Most prior studies of age differences in WM have used diffusion tensor imaging (DTI), but typical DTI metrics (e.g., fractional anisotropy; FA) can reflect multiple neurobiological features, making interpretation challenging. Here, we used fixel-based analysis (FBA) to investigate age-related WM differences observed using DTI in a sample of 45 older and 25 younger healthy adults. Age-related FA differences were widespread but were strongly associated with differences in multi-fiber complexity (CX), suggesting that they reflected differences in crossing fibers in addition to structural differences in individual fiber segments. FBA also revealed a frontolimbic locus of age-related effects and provided insights into distinct microstructural changes underlying them. Specifically, age differences in fiber density were prominent in fornix, bilateral anterior internal capsule, forceps minor, body of the corpus callosum, and corticospinal tract, while age differences in fiber cross section were largest in cingulum bundle and forceps minor. These results provide novel insights into specific structural differences underlying major WM differences associated with aging.

Microstructural White Matter Alterations in Cognitively Impaired Patients at Early Stages of Multiple Sclerosis

PurposeAs conventional quantitative magnetic resonance imaging (MRI) parameters are weakly associated with cognitive impairment (CI) in early multiple sclerosis (MS), we explored microstructural white matter alterations in early MS or clinically isolated syndrome (CIS) comparing patients with or without CI.MethodsBased on a preceding tract-based spatial statistics analysis (3 Tesla MRI) which contrasted 106 patients with early MS or CIS and 49 healthy controls, diffusion metrics (fractional anisotropy, FA, mean diffusivity, MD) were extracted from significant clusters using an atlas-based approach. The FA and MD were compared between patients with (Ci_P n = 14) and without (Cp_P n = 81) cognitive impairment in a subset of patients who underwent CI screening.ResultsThe FA was reduced in Ci_P compared to Cp_P in the splenium of corpus callosum (p = 0.001), right parahippocampal cingulum (p = 0.002) and fornix cres./stria terminalis (0.042), left posterior corona radiata (p = 0.012), bilateral cerebral peduncles, medial lemniscus and in cerebellar tracts. Increased MD was detected in the splenium of corpus callosum (p = 0.01). The CI-related localizations overlapped only partially with MS lesions.ConclusionMicrostructural white matter alterations at disease onset were detectable in Ci_P compared to Cp_P in known cognitively relevant fiber tracts, indicating the relevance of early treatment initiation in MS and CIS.

White matter alterations in glaucoma and monocular blindness differ outside the visual system

The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test–retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss.

White matter microstructure and its relation to clinical features of obsessive\u2013compulsive disorder: findings from the ENIGMA OCD Working Group

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Correlations between Dual-Pathway White Matter Alterations and Language Impairment in Patients with Aphasia: A Systematic Review and Meta-analysis.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.