White Matter Organization Research Articles

Home language and literacy environment and its relationship to socioeconomic status and white matter structure in infancy.

The home language and literacy environment (HLLE) in infancy has been associated with subsequent pre-literacy skill development and HLLE at preschool-age has been shown to correlate with white matter organization in tracts that subserve pre-reading and reading skills. Furthermore, childhood socioeconomic status (SES) has been linked with both HLLE and white matter organization. It is important to understand whether the relationships between environmental factors such as HLLE and SES and white matter organization can be detected as early as infancy, as this period is characterized by rapid brain development that may make white matter pathways particularly susceptible to these early experiences. Here, we hypothesized that HLLE(1) relates to white matter organization in pre-reading and reading-related tracts in infants, and (2) mediates a link between SES and white matter organization. To test these hypotheses, infants (mean age: 8.6 ± 2.3months, N = 38) underwent diffusion-weighted imaging MRI during natural sleep. Image processing was performed with an infant-specificpipeline andfractional anisotropy (FA) was estimated from the arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF) bilaterally using thebaby automated fiber quantification method. HLLE was measured with the Reading subscale of the StimQ (StimQ-Reading) and SES was measured with years of maternal education. Self-reported maternal reading ability was also quantified and applied to our statistical models as a proxy for confounding genetic effects. StimQ-Reading positively correlated with FA in left AF and to maternal education, but did not mediate the relationship between them. Taken together, these findings underscore the importance of considering HLLE from the start of life and may inform novel prevention and intervention strategies to support developing infants during a period of heightened brain plasticity.

The association of white matter connectivity with prevalence, incidence and course of depressive symptoms: The Maastricht Study.

Altered white matter brain connectivity has been linked to depression. The aim of this study was to investigate the association of markers of white matter connectivity with prevalence, incidence and course of depressive symptoms. Markers of white matter connectivity (node degree, clustering coefficient, local efficiency, characteristic path length, and global efficiency) were assessed at baseline by 3 T MRI in the population-based Maastricht Study (n = 4866; mean ± standard deviation age 59.6 ± 8.5 years, 49.0% women; 17 406 person-years of follow-up). Depressive symptoms (9-item Patient Health Questionnaire; PHQ-9) were assessed at baseline and annually over seven years of follow-up. Major depressive disorder (MDD) was assessed with the Mini-International Neuropsychiatric Interview at baseline only. We used negative binominal, logistic and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle risk factors. A lower global average node degree at baseline was associated with the prevalence and persistence of clinically relevant depressive symptoms [PHQ-9 ⩾ 10; OR (95% confidence interval) per standard deviation = 1.21 (1.05-1.39) and OR = 1.21 (1.02-1.44), respectively], after full adjustment. On the contrary, no associations were found of global average node degree with the MDD at baseline [OR 1.12 (0.94-1.32) nor incidence or remission of clinically relevant depressive symptoms [HR = 1.05 (0.95-1.17) and OR 1.08 (0.83-1.41), respectively]. Other connectivity measures of white matter organization were not associated with depression. Our findings suggest that fewer white matter connections may contribute to prevalent depressive symptoms and its persistence but not to incident depression. Future studies are needed to replicate our findings.

Disrupted Brain Structural Network Connection in de novo Parkinson's Disease With Rapid Eye Movement Sleep Behavior Disorder.

ObjectiveTo explore alterations in white matter network topology in de novo Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD).Materials and MethodsThis study included 171 de novo PD patients and 73 healthy controls (HC) recruited from the Parkinson's Progression Markers Initiative (PPMI) database. The patients were divided into two groups, PD with probable RBD (PD-pRBD, n = 74) and PD without probable RBD (PD-npRBD, N = 97), according to the RBD screening questionnaire (RBDSQ). Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group.ResultsAll three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency (Ne) were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients.ConclusionsPD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD.

The brain of the tree pangolin (Manis tricuspis). IX. The pallial telencephalon.

A cyto‐, myelo‐, and chemoarchitectonic analysis of the pallial telencephalon of the tree pangolin is provided. As certain portions of the pallial telencephalon have been described previously (olfactory pallium, hippocampal formation, and amygdaloid complex), we focus on the claustrum and endopiriform nuclear complex, the white matter and white matter interstitial cells, and the areal organization of the cerebral cortex. Our analysis indicates that the organization of the pallial telencephalon of the tree pangolin is similar to that observed in many other mammals, and specifically quite similar to the closely related carnivores. The claustrum of the tree pangolin exhibits a combination of insular and laminar architecture, while the endopiriform nuclear complex contains three nuclei, both reminiscent of observations made in other mammals. The population of white matter interstitial cells resembles that observed in other mammals, while a distinct laminated organization of the intracortical white matter was revealed with parvalbumin immunostaining. The cerebral cortex of the tree pangolin presented with indistinct laminar boundaries as well as pyramidalization of the neurons in both layers 2 and 4. All cortical regions typically found in mammals were present, with the cortical areas within these regions often corresponding to what has been reported in carnivores. Given the similarity of the organization of the pallial telencephalon of the tree pangolin to that observed in other mammals, especially carnivores, it would be reasonable to assume that the neural processing afforded the tree pangolin by these structures does not differ dramatically to that of other mammals.

Aberrant White Matter Organization Correlated With Neurodevelopment Outcomes in Tetralogy of Fallot: An Atlas-Based Diffusion Tensor Imaging Study

BackgroundWhite matter injury (WMI) and impaired neurodevelopment are common in children with congenital heart disease. However, the effect of WMI on neurodevelopmental outcomes is still rarely reported. In this study, we aimed to investigate microstructural changes in white matter (WM) and its relationship with neurodevelopmental outcomes and further explore the underlying neurophysiological mechanisms of neurocognitive impairments in the tetralogy of Fallot (ToF). MethodDiffusion tensor imaging (DTI) data were acquired in preschool-aged children with ToF (n = 29) and normal controls (NC, n = 19), and neurodevelopmental assessments were performed with the Wechsler Preschool and Primary Scale of Intelligence in ToF. The differences in DTI metrics including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were evaluated between ToF and NC. Correlations between WM microstructural changes and neurodevelopmental outcomes were further analyzed. ResultsSignificant WM differences were found in the uncinate fasciculus, cingulum hippocampus, superior longitudinal fasciculus, and corticospinal tract between children with ToF and NC. Impaired WM integrity was correlated with the verbal comprehension index and working memory index in ToF. ConclusionsThis study demonstrated WM microstructure injury, and this injury is related to worse language and working memory performance in preschool-aged children with ToF. These findings suggested that DTI metrics may be a potential biomarker of neurocognitive impairments in ToF and can be used to predict future neurodevelopmental outcomes, which also provide new insights into the underlying neurophysiological mechanisms of neurocognitive impairments in ToF.

Topological Alteration Is Associated with Non-dependent Alcohol Use in Bipolar Disorder.

Introduction: Structural alterations in cortical thickness and the microstructural organization of white matter are independently associated with non-dependent alcohol consumption and bipolar disorder (BD). Identifying their interactive and network-level effects on brain topology may identify the impact of alcohol on reward and emotion circuitry, and its contribution to relapse in BD. Materials and Methods: Thirty-four BD-I (DSM-IV-TR) and 38 healthy controls (HC) underwent T1 and diffusion-weighted magnetic resonance imaging scanning, and the Alcohol Use Disorders Identification Test-Consumption to assess alcohol use. Connectomes comprising 34 cortical and 9 subcortical nodes bilaterally (Freesurfer v5.3) connected by fractional anisotropy-weighted edges derived from non-tensor based deterministic constrained spherical deconvolution tractography (ExploreDTI v4.8.6) underwent permutation-based topological analysis (NBS v1.2) and were examined for the effects of alcohol use and diagnosis-by-alcohol use accounting for age, sex, and diagnosis. Results: Alcohol was significantly related to a subnetwork, encompassing connections between fronto-limbic, basal ganglia, and temporal nodes (Frange = 5-8.4, p = 0.031) and it was not detected to have an effect on global brain integration or segregation. A portion of this network (18%), involving cortico-limbic and basal ganglia connections, was differentially impacted by alcohol in the BD relative to the control group (Frange = 5-8.8, p = 0.033), despite the groups' consuming similar amounts of alcohol (BD: mean ± standard deviation 4.95 ± 3.0; HC 3.62 ± 3.0, T = 1.88, p = 0.06). Discussion: Non-dependent alcohol use impacts brain architectural organization and connectivity within salience, reward, and affective circuitry. The relationship between alcohol use and topology of the network in BD suggests an interactive effect between specific biological vulnerability and alcohol use, which may explain the susceptibility to an increased risk of relapse in the disorder. Impact statement The association between non-dependent alcohol use and neural architecture in bipolar disorder (BD) is unknown, despite the poor clinical trajectory and increased likelihood of relapse associated with alcohol use in BD. We demonstrate that together alcohol and a diagnosis of BD is associated with a subnetwork involving nodes of the cortico-limbic and reward networks. This subnetwork, demonstrated in BD and absent in controls, differentially involves nodes that are specific to reward and emotion processes. This suggests a diagnosis-specific biological vulnerability for alcohol use and may be consistent with known mood lability and thus relapse associated with alcohol use in BD.

Alterations in the inferior fronto-occipital fasciculus - a specific neural correlate of gender incongruence?

Increasing numbers of adolescents seek help for gender-identity questions. Consequently, requests for medical treatments, such as puberty suppression, are growing. However, studies investigating the neurobiological substrate of gender incongruence (when birth-assigned sex and gender identity do not align) are scarce, and knowledge about the effects of puberty suppression on the developing brain of transgender youth is limited. Here we cross-sectionally investigated sex and gender differences in regional fractional anisotropy (FA) as measured by diffusion MR imaging, and the impact of puberty on alterations in the white-matter organization of 35 treatment-naive prepubertal children and 41 adolescents with gender incongruence, receiving puberty suppression. The transgender groups were compared with 79 age-matched, treatment-naive cisgender (when sex and gender align) peers. We found that transgender adolescents had lower FA in the bilateral inferior fronto-occipital fasciculus (IFOF), forceps major and corpus callosum than cisgender peers. In addition, average FA values of the right IFOF correlated negatively with adolescents' cumulative dosage of puberty suppressants received. Of note, prepubertal children also showed significant FA group differences in, again, the right IFOF and left cortico-spinal tract, but with the reverse pattern (transgender > cisgender) than was seen in adolescents. Importantly, our results of lower FA (indexing less longitudinal organization, fiber coherence, and myelination) in the IFOF of gender-incongruent adolescents replicate prior findings in transgender adults, suggesting a salient neural correlate of gender incongruence. Findings highlight the complexity with which (pubertal) sex hormones impact white-matter development and add important insight into the neurobiological substrate associated with gender incongruence.

Distinctive neural correlates of phonological and reading impairment in fetal alcohol-exposed adolescents with and without facial dysmorphology

Prenatal alcohol exposure (PAE) has been linked to atypical brain and cognitive development, including poor academic performance in reading. This study utilized functional magnetic resonance imaging and diffusion tensor imaging to characterize functional and structural mechanisms mediating reading deficits in 26 adolescents with PAE-related facial dysmorphology (fetal alcohol syndrome (FAS)/partial FAS (PFAS)), 29 heavily-exposed (HE) non-syndromal adolescents, in comparison with 19 typically developing controls. The FAS/PFAS and HE groups were balanced in terms of levels of PAE and reading (dis)ability. While neural alterations in the posterior association cortices were evident in both PAE groups, distinctive neural correlates of reading (dis)abilities were observed between adolescents with and without facial dysmorphology. Specifically, compared to the HE and control groups, the syndromal adolescents showed greater activation in the right precentral gyrus during phonological processing and rightward lateralization in an important reading-related tract (inferior longitudinal fasciculus, ILF), suggesting an atypical reliance on the right hemisphere. By contrast, in the HE, better reading skills were positively correlated with neural activation in the left angular gyrus and white matter organization of the left ILF, although the brain function-behavior relation was weaker than among the controls, suggesting less efficient function of the typical reading network. Our findings provide converging evidence at both the neural functional and structural levels for distinctive brain mechanisms underlying atypical reading and phonological processing in PAE adolescents with and without facial dysmorphology.

The Role Of Osteopontin In Patients With Type 2 Diabetes And Cognitive Impairment

Background — type 2 diabetes is associated with obesity and cardiovascular disease; in combination with dysmetabolic and proinflammatory pathophysiological mechanisms, it leads to cognitive impairment. Objective — analysis of the osteopontin role in formation of cognitive disorders in patients with type 2 diabetes. Material and Methods — the study complies with generally accepted ethical rules; it was approved by the Ethics Committee of Siberian State Medical University. It involved 50 patients with type 2 diabetes, who were divided into groups depending on the presence of cognitive impairment; the control group consisted of 25 subjects. All patients underwent general clinical examination, blood sampling for biochemical parameters, and plasma osteopontin content assessment. Magnetic resonance imaging (MRI) was performed on SIGNA Creator E magnetic resonance imaging system, GE Healthcare, 1.5 T, China. The employed techniques included dynamic contrast and arterial spin labeling, proton spectroscopy, tractography. SPSS Statistics software was used for statistical analysis. Results — osteopontin levels were higher in patients with excess weight, hyperglycemia, hyperuricemia, dyslipidemia, and cognitive impairment; and in neuroimaging studies with microangiopathy, based on perfusion MRI, with impaired white matter integration, as well as with neurometabolism of choline, creatine and phosphocreatine metabolites in the hippocampus, as well as their NAA/Cr, NAA/Cho, Cho/Cr ratios (p≤0.05). Conclusion — patients with type 2 diabetes, along with cognitive and metabolic disorders, exhibited elevated levels of osteopontin, which was also associated with impaired cerebral vascularization in general, and white matter organization, as well as neurometabolism in the hippocampus.

White matter network structure as a substrate of cognitive brain reserve in cerebral small‐vessel disease: The Maastricht Study

AbstractMethodThe Maastricht Study is a population‐based cohort study with extensive phenotyping, enriched for type‐2 diabetes. Cognitive test scores, structural connectivity data, and 3T MRI were available for n=4798 participants (mean age(±SD)=59.2(±8.7), 50.0% male). Images were assessed by Fazekas score (£1 or ≥2), presence of microbleeds and lacunar infarcts in terms of dichotomous measures, and combined into a cSVD score (range 0‐3). Node degree (ND), a measure of the mean interconnectedness of nodes in the structural connectome, was used as connectivity score. A composite cognition score (CS) was taken as the mean score across three cognitive domains (Memory, Information Processing Speed and Executive Function). Multivariable linear regression analyses were used to investigate the interaction effect between ND and cSVD score on CS, adjusted for age, sex, education, and diabetes status.ResultHigher cSVD score was associated with lower CS. ND modified the association between cSVD score and CS in the adjusted model (p for interaction p<0.004). While there were clear cognitive differences across cSVD levels if ND was low, the association between cSVD and cognition was attenuated in a dose‐response fashion with increasing ND (Figure 1).ConclusionStructural ND provides evidence of an individual’s CR based on white matter organization in the presence of damage from cSVD. Even in participants with the highest cSVD burden, sufficiently high ND score was associated with normal CS.

Advanced diffusion‐MRI models reveals sex‐specific differences in white matter organization in patients with mild cognitive impairment

AbstractBackgroundRecent literature suggests that free‐water corrected (fiso) diffusion MRI (dMRI) measures provide higher sensitivity as compared to conventional single‐tensor (ST) dMRI measures to understand white‐matter (WM) changes due to neurodegeneration. However, fiso‐corrected dMRI measures are still biased at crossing‐fiber regions (CFR) of WM which are shown to be around 90% of the total WM voxels with conventional dMRI data acquisition. In this study, we systematically compared dMRI measures from ST‐dMRI, fiso‐corrected ST‐dMRI measures, and measures from advanced dMRI models such as Diffusion Kurtosis Imaging (DKI) and Neurite Orientation Distribution and Density Imaging (NODDI) which are sensitive to CFRs. We hypothesize that these advanced dMRI models will be sensitive in understanding sex‐specific WM organizational changes at regional level in patients with Alzheimer’s disease (AD)‐related mild cognitive impairment (MCI).Method40 healthy controls [HC; 21 Females (F), 19 Males (M)] and 38 MCI participants [13F, 25 M] were recruited at our center. MCI diagnoses were based on expert consensus between a neurologist (AR) and a neuropsychologist (JC) using results of a neuropsychological test battery and the Clinical Dementia Rating (CDR) interview. Isotropic 1.5mm3 multi‐shell dMRI (b‐values=500s/mm2, 1000s/mm2, and 2500s/mm2) each with identical 71 diffusion‐encoding directions was acquired on a 3T Siemens Skyra scanner for every participant using the CMRR sequence. 8 uniformly interspersed non‐diffusion‐weighted (b0) images were also acquired in the same run. ST, fiso‐corrected, DKI, and NODDI dMRI measures were estimated for every brain voxel in‐house using the standard analytic tools. WM was skeletonized using FSL tools and statistical comparisons were done non‐parametrically using PALM tools. GLM was utilized to test for sex‐specific group effect. Significance was established at family‐wise error correction (FWE) pcorr<0.05.ResultThalamocortical tracts of males in both HC and MCI showed a significantly higher axonal kurtosis (AK) and orientation density (ODI) derived from DKI and NODDI when compared to within‐group females. DKI also revealed presence of higher axonal water fraction (AWF) along the entire WM‐tracts between HC‐female and HC‐male, and lower mean kurtosis (MK) along the thalamic‐cortical tracts in HC‐females as compared to MCI‐females.ConclusionAdvanced dMRI‐models are sensitive to understand sex‐specific WM disorganization due to healthy ageing and MCI.

A model of tension-induced fiber growth predicts white matter organization during brain folding

The past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity.

Osteopontin in patients with metabolic syndrome and cognitive impairment

Metabolic syndrome is associated with dysmetabolic and proinflammatory pathophysiological mechanisms, which lead to cognitive impairment. Evaluation of the effect of osteopontin as a predictor of these changes with the analysis of the neuroimaging pattern of the brain is of interest.Purpose of the study: analysis of the role of osteopontin in patients with metabolic syndrome in the formation of cognitive impairment.Material and Methods: the study complies with generally accepted ethical rules and included 50 patients with type metabolic syndrome (which were divided into groups according to cognitive impairment) and 25 control groups. All underwent a general clinical examination, blood sampling for biochemical parameters, including osteopontin. Magnetic resonance imaging (MRI) was performed on a Signa Creator "E" magnetic resonance tomograph, GE Healthcare, 1.5 Tesla, China: techniques were dynamic contrast and arterial spin labels, proton spectroscopy, tractography. SPSS Statistic program was used for statistical analysis.Results: osteopontin was higher in patients with overweight, hyperglycemia, hyperuricemia, dyslipidemia, and cognitive impairment, and in the neuroimaging study with microangiopathy according to perfusion MRI, impaired integration of the white matter of the brain, as well as neurometabolism in the hippocampal region by choline, creatine and phosphocreatine metabolites in the hippocampal region, as well as their NAA/Cr, NAA/Cho, Cho/Cr ratios (p≤0.05).Conclusion: patients with metabolic syndrome and cognitive disorders revealed elevated levels of osteopontin, which is also associated with impaired cerebral vascularization in general and white matter organization, as well as neurometabolism in the hippocampus..

Connectivity gradients on tractography data: Pipeline and example applications.

Gray matter connectivity can be described in terms of its topographical organization, but the differential role of white matter connections underlying that organization is often unknown. In this study, we propose a method for unveiling principles of organization of both gray and white matter based on white matter connectivity as assessed using diffusion magnetic ressonance imaging (MRI) tractography with spectral embedding gradient mapping. A key feature of the proposed approach is its capacity to project the individual connectivity gradients it reveals back onto its input data in the form of projection images, allowing one to assess the contributions of specific white matter tracts to the observed gradients. We demonstrate the ability of our proposed pipeline to identify connectivity gradients in prefrontal and occipital gray matter. Finally, leveraging the use of tractography, we demonstrate that it is possible to observe gradients within the white matter bundles themselves. Together, the proposed framework presents a generalized way to assess both the topographical organization of structural brain connectivity and the anatomical features driving it.

N-3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development.

Westernization of dietary habits has led to a progressive reduction in dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs). Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental disorders, conditions in which myelination processes are abnormal, leading to defects in brain functional connectivity. Only little is known about the role of n-3 PUFAs in oligodendrocyte physiology and white matter development. Here, we show that lifelong n-3 PUFA deficiency disrupts oligodendrocytes maturation and myelination processes during the postnatal period in mice. This has long-term deleterious consequences on white matter organization and hippocampus-prefrontal functional connectivity in adults, associated with cognitive and emotional disorders. Promoting developmental myelination with clemastine, a first-generation histamine antagonist and enhancer of oligodendrocyte precursor cell differentiation, rescues memory deficits in n-3 PUFA deficient animals. Our findings identify a novel mechanism through which n-3 PUFA deficiency alters brain functions by disrupting oligodendrocyte maturation and brain myelination during the neurodevelopmental period.

Association between white matter organization and cognitive performance in athletes with a history of sport-related concussion

ABSTRACT Introduction Impairments in cognitive performance after sport-related concussion (SRC) typically resolve within weeks of the injury, whereas alterations to white matter (WM) organization have been found to persist longer into the chronic injury stage. However, longer-term associations between cognition and WM organization following SRC have not been studied. The objective of this study was to compare WM organization and cognitive performance in collegiate athletes an average of almost 4 years post-SRC to athletes with no history of SRC. Method National Collegiate Athletic Association Division III athletes (n = 71, age = 19.3 ± 1.2; 14 with self-reported SRC) completed a neurocognitive assessment and diffusion tensor imaging (DTI). WM organization was assessed by extracting measures of fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) from 20 WM regions of interest (ROIs). Multivariate partial least squares analyses were used to compare athletes with and without a history of SRC and assess relationships between DTI-derived metrics of WM organization and cognitive measures. Results Cognitive performance and ROI metrics did not differ between athletes with and without prior SRC. However, among athletes with a history of SRC, better executive function, processing speed, and memory but worse choice reaction time were associated with higher FA and lower MD and RD in several WM tracts. Conclusion Athletes with a history of SRC demonstrated greater associations between cognitive performance and WM organization, but also variability in the domains showing associations. Taken together, the findings demonstrate the importance of examining brain-behavior relationships several years after SRC to better gauge how WM organization supports cognition.

Progressive brain microstructural damage in patients with multiple sclerosis but not in patients with neuromyelitis optica spectrum disorder: A cross-sectional and follow-up tract-based spatial statistics study

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) may sometimes be misdiagnosed as multiple sclerosis (MS) because both disorders have similar clinical presentations and commonly show white matter damage in the brain. Diffusion tensor imaging (DTI) is an advanced MRI technique to assess the microstructural organization of white matter and provides greater pathological specificity than conventional MRI. In the present combined cross-sectional and longitudinal study, the novel DTI technique of Track-Based Spatial Statistics (TBSS) was used to investigate the difference of DTI parameter abnormalities between NMOSD and MS. MethodsA total of 42 patients with NMOSD, 51 patients with MS and 56 health controls (HC) were recruited and of these 14 patients with NMOSD and 13 patients with MS were also studied at follow-up after an average interval of approximately one year. Measurements of fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) were compared at baseline and follow-up in patients with NMOSD and MS. ResultsSignificant reduction in FA, increase in MD, AD and RD were observed in patients with MS (p < 0.05) and reduced FA was shown in NMOSD (p < 0.05) compared to HC, with all the effects, together with lesion load on T1WI and T2WI, being greater in patients with MS than in patients with NMOSD (p < 0.05). There was no significant difference in the time interval to follow-up in patients with MS (1.37 years) and NMOSD (1.25 years) (p > 0.05), during which there were significant changes in EDSS score between baseline and follow-up in NMOSD and MS patients (p < 0.05). There was a significantly reduced FA, and increased MD and RD in patients with MS (p < 0.05), but no significant changes in patients with NMOSD (p > 0.05). ConclusionsBoth MS and NMOSD have microstructure damage in white matter, while the progressive change in brain microstructural properties is observed in patients with MS but may not in patients with NMOSD in a short-term follow-up.

White Matter Microstructural Properties of the Cerebellar Peduncles Predict Change in Symptoms of Psychopathology in Adolescent Girls.

Internalizing symptoms typically emerge in adolescence and are more prevalent in females than in males; in contrast, externalizing symptoms typically emerge in childhood and are more commonly observed in males. Previous research has implicated aspects of white matter organization, including fractional anisotropy (FA), of cerebral tracts in both internalizing and externalizing symptoms. Although the cerebellum has been posited to integrate limbic and cortical regions, its role in psychopathology is not well understood. In this longitudinal study, we investigated whether FA of the superior (SCP), middle (MCP), and inferior cerebellar peduncles (ICP) predict change in symptoms and whether sex moderates this association. One hundred eleven adolescents completed the Youth Self-Report, assessing symptoms at baseline (ages 9-13years) and again 2years later. Participants also underwent diffusion-weighted imaging at baseline. We used deterministic tractography to segment and compute mean FA of the cerebellar peduncles. Lower FA of the right SCP at baseline predicted increases in internalizing symptoms in females only. Lower FA in the right SCP and ICP also predicted increases in externalizing symptoms in females, but these associations did not survive multiple comparison correction. There was no association between FA of the cerebellar peduncles and change in symptoms in males or between MCP FA and symptom changes in males or females. Organizational properties of the SCP may be a sex-specific marker of internalizing symptom changes in adolescence. The cerebellar peduncles should be explored further in future studies to elucidate sex differences in symptoms.

Disrupted Topological Organization in White Matter Networks in Unilateral Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a sudden-onset hearing impairment that rapidly develops within 72 h and is mostly unilateral. Only a few patients can be identified with a defined cause by routine clinical examinations. Recently, some studies have shown that unilateral SSNHL is associated with alterations in the central nervous system. However, little is known about the topological organization of white matter (WM) networks in unilateral SSNHL patients in the acute phase. In this study, 145 patients with SSNHL and 91 age-, gender-, and education-matched healthy controls were evaluated using diffusion tensor imaging (DTI) and graph theoretical approaches. The topological properties of WM networks, including global and nodal parameters, were investigated. At the global level, SSNHL patients displayed decreased clustering coefficient, local efficiency, global efficiency, normalized clustering coefficient, normalized characteristic path length, and small-worldness and increased characteristic path length (p < 0.05) compared with healthy controls. At the nodal level, altered nodal centralities in brain regions involved the auditory network, visual network, attention network, default mode network (DMN), sensorimotor network, and subcortical network (p < 0.05, Bonferroni corrected). These findings indicate a shift of the WM network topology in SSNHL patients toward randomization, which is characterized by decreased global network integration and segregation and is reflected by decreased global connectivity and altered nodal centralities. This study could help us understand the potential pathophysiology of unilateral SSNHL.

Sex differences in myelin content of white matter tracts in adolescents with depression.

Depression is a chronic and debilitating condition that often emerges during adolescence, a period of significant brain maturation. Few studies, however, have examined how mechanisms of neuroplasticity, including myelination, are affected by adolescent-onset depression. Here, we used multimodal MR imaging to characterize myelin, indexed by R1, in white matter tracts previously associated with depression and compare 48 adolescents with lifetime depression (45 with current depression, 3 remitted) and 35 healthy controls in R1. Compared to healthy controls, R1 was higher in adolescents with lifetime depression in the uncinate fasciculus and corpus callosum genu (all βs > 0.42; all ps < 0.037). Sex significantly moderated the association between depression and R1 in the left uncinate fasciculus and corpus callosum genu (all βs > 0.86; all ps < 0.02), such that depressed female adolescents had significantly higher R1 in these tracts than did healthy female adolescents (all βs > 0.82; all ps < 0.0012). In contrast, depressed and non-depressed male adolescents did not differ in R1 in these tracts (all ps > 0.32). While fractional anisotropy (FA), a commonly examined measure of white matter organization based on diffusion-weighted MRI, in the left uncinate was positively associated with lifetime depression in our sample (β = 0.56; p = 0.016), we found no evidence of sex-specific effects of depression in FA. Our results suggest that R1 is more sensitive to sex-specific effects of depression than FA, particularly in female adolescents. Given evidence that myelin inhibits synapse formation and reduces brain plasticity, our findings implicate experience-driven regional myelination as a mechanism underlying depression during periods of significant neural maturation such as adolescence.