Impaired White Matter Integrity Research Articles

Structural and Functional Brain Imaging in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia Treated With Chemotherapy: A Systematic Review.

BackgroundThe effect of chemotherapy on brain development in long-term survivors of pediatric acute lymphoblastic leukemia (ALL) was systematically reviewed.MethodsA systematic search of Pubmed, Scopus, and PsycINFO databases was conducted to identify articles published between January 2000 and February 2020 that implemented magnetic resonance imaging to assess brain structure and function in pediatric ALL survivors (diagnosed younger than 21 years of age). The review included articles that were published on children diagnosed with ALL between 0 and 21 years of age and treated with chemotherapy-only protocols. Articles meeting the inclusion criteria described survivors on average of 5 years or more from diagnosis and were peer-reviewed articles and original studies.ResultsThe search yielded 1975 articles with 23 articles meeting inclusion criteria. The review revealed that survivors had statistically significant alterations in brain anatomy, most commonly a smaller hippocampus and impaired microstructural white matter integrity in frontal brain regions. Survivors also had impaired brain function including lower brain network efficiency and altered resting state connectivity. Survivors also displayed widespread reductions in brain activation (ie, frontal, temporal, parietal brain regions) during cognitive tasks.ConclusionAlthough the neurotoxic effects of cancer treatment are reduced in the absence of cranial radiation, survivors treated on chemotherapy-only protocols still display long-term alterations in brain structure and function, which contribute to lifelong neurocognitive late effects.

Evaluation of White Matter Tracts in Autistic Individuals: A Review of Diffusion Tensor Imaging Studies

Introduction: Many cognitive and social deficits in autism are caused by abnormal functional connections between brain networks, which are manifested by impaired integrity of white matter tracts. White matter tracts are like the "highways" of the brain, which allow fast and efficient communication in different areas of the brain. The purpose of this article is to review the results of autism studies that have used diffusion tensor images (DTI). Diffusion tensor images is a neuroimaging technique to examine the integrity of tracts. Conclusion: The results of these studies suggest that neural tracts can be abnormal in people with Autism spectrum disorder (ASD) due to impaired white matter integrity. Thus, changes in these tracts in the brains of people with ASD are helpful in identifying individual differences. Although most studies have reported decreased FA and increased MD, RD, and AD in white matter tracts, some studies have reported increased FA or no significant difference between the control and autistic groups.

Kinesin-1-mediated axonal transport of CB1 receptors is required for cannabinoid-dependent axonal growth and guidance.

Endocannabinoids (eCB) modulate growth cone dynamics and axonal pathfinding through the stimulation of cannabinoid type-1 receptors (CB1R), the function of which depends on their delivery and precise presentation at the growth cone surface. However, the mechanism involved in the axonal transport of CB1R and its transport role in eCB signaling remains elusive. As mutations in the kinesin-1 molecular motor have been identified in patients with abnormal cortical development and impaired white matter integrity, we studied the defects in axonal pathfinding and fasciculation in mice lacking the kinesin light chain 1 (Klc1-/-) subunit of kinesin-1. Reduced levels of CB1R were found in corticofugal projections and axonal growth cones in Klc1-/- mice. By live-cell imaging of CB1R-eGFP we characterized the axonal transport of CB1R vesicles and described the defects in transport that arise after KLC1 deletion. Cofilin activation, which is necessary for actin dynamics during growth cone remodeling, is impaired in the Klc1-/- cerebral cortex. In addition, Klc1-/- neurons showed expanded growth cones that were unresponsive to CB1R-induced axonal elongation. Together, our data reveal the relevance of kinesin-1 in CB1R axonal transport and in eCB signaling during brain wiring.

Brain Structural and Functional Alterations Specific to Low Sleep Efficiency in Major Depressive Disorder.

BackgroundSleep disturbance is common in patients with major depressive disorder (MDD), but the exploration of its neural underpinnings is limited by subjective sleep measurement and single-modality neuroimaging analyses.MethodsNinety six patients with MDD underwent polysomnography examinations and multi-modal magnetic resonance imaging (MRI) scans. According to sleep efficiency, patients were subdivided into well-matched normal sleep efficiency (NSE, N = 42; 14 men; aged 43 ± 10 years) and low sleep efficiency (LSE, N = 54; 23 men; aged 45 ± 12 years) groups. Inter-group differences in brain structure and function were examined by applying voxel-based morphometry (VBM), regional homogeneity (ReHo) and functional connectivity strength (FCS), and tract-based spatial statistics (TBSS) approaches to structural, functional, and diffusion MRI data, respectively.ResultsThere was no significant difference in gray matter volume (GMV) between the NSE and LSE groups. Compared with the NSE group, the LSE group showed increased axial diffusivity in the left superior and posterior corona radiata, and left posterior limb and retrolenticular part of internal capsule. In addition, the LSE group exhibited decreased ReHo in the bilateral lingual gyri and right postcentral gyrus yet increased FCS in the left angular gyrus relative to the NSE group. Moreover, validation analyses revealed that these results remained after adjusting for the medication effect.ConclusionOur data indicate that preserved gray matter morphology, impaired white matter integrity, and decreased local synchronization degree yet increased FCS are specific to low SE in MDD patients. These findings of disassociation between structural and functional alterations might provide insights into the neural mechanisms of sleep disturbance in depression.

Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

Cross-sectional studies have repeatedly shown impaired white matter integrity in patients with major depressive disorder. Longitudinal analyses are missing from the current research and are crucial to elucidating the impact of disease trajectories on white matter impairment in major depressive disorder. Fifty-nine patients with major depressive disorder receiving inpatient treatment, as well as 49 healthy controls, took part in a prospective study. Participants were scanned twice (baseline and follow-up), approximately 2.25 years apart, using diffusion tensor imaging. We analyzed diffusion metrics using tract-based spatial statistics. At baseline, patients had higher mean diffusivity in a large bilateral frontal cluster comprising the body and genu of the corpus callosum, the anterior and superior corona radiata, and the superior longitudinal fasciculus. A significant group × time interaction revealed a decrease of mean diffusivity in patients with major depressive disorder over time, abolishing group differences at follow-up. This effect was observed irrespective of disease course in the follow-up period. Analyzing the course of illness is challenging because of recollection biases in patients with major depressive disorder. This study reports follow-up diffusion tensor imaging data in patients with major depressive disorder after an acute depressive episode. We demonstrated impaired prefrontal white matter microstructure (higher mean diffusivity) at baseline in patients with major depressive disorder, which normalized at follow-up after 2 years, irrespective of disease course. This might have been due to a general treatment effect and might have reflected recovery of white matter integrity.

Sensorimotor and pain-related alterations of the gray matter and white matter in Type 2 diabetic patients with peripheral neuropathy.

Although diabetic peripheral neuropathy (DPN) has long been considered a disease of the peripheral nervous system, recent neuroimaging studies have shown that alterations in the central nervous system may play a crucial role in its pathogenesis. Here, we used surface‐based morphometry (SBM) and tract‐based spatial statistics (TBSS) to investigate gray matter (GM) and white matter (WM) differences between patients with DPN (n = 67, 44 painless and 23 painful) and healthy controls (HCs; n = 88). Compared with HCs, patients with DPN exhibited GM abnormalities in the pre‐ and postcentral gyrus and in several deep GM nuclei (caudate, putamen, medial pallidum, thalamus, and ventral nuclear). They also exhibited altered WM tracts (corticospinal tract, spinothalamic tract, and thalamocortical projecting fibers). These findings suggest impaired motor and somatosensory pathways in DPN. Further, patients with DPN (particularly painful DPN) exhibited morphological differences in the cingulate, insula, prefrontal cortex, and thalamus, as well as impaired WM integrity in periaqueductal WM and internal and external capsules. This suggests pain‐perception/modulation pathways are altered in painful DPN. Intermodal correlation analyses found that the morphological indices of the brain regions identified by the SBM analysis were significantly correlated with the fractional anisotropy of brain regions identified by the TBSS analysis, suggesting that the GM and WM alterations were tightly coupled. Overall, our study showed sensorimotor and pain‐related GM and WM alterations in patients with DPN, which might be involved in the development of DPN.

Impaired white matter integrity between premotor cortex and basal ganglia in writer's cramp.

IntroductionWriter’s cramp (WC) as a focal hand dystonia is characterized by abnormal postures of the hand during writing. Impaired inhibition and maladaptive plasticity in circuits linking the basal ganglia and sensorimotor cortices have been described. In particular, a dysfunction of lateral premotor cortices has been associated with impaired motor control in WC. We applied diffusion tensor imaging to identify changes in white matter connectivity between premotor regions and important cortical and subcortical structures.MethodsWhole brain white matter tracts were reconstructed in 18 right‐handed WC patients and 18 matched controls, using probabilistic fiber tracking. We restricted our analyses to left‐hemispheric fibers between the middle frontal gyrus (MFG) and basal ganglia, thalamus, primary motor, and sensory cortex. Diffusion parameters (fractional anisotropy and linear anisotropy) were compared between both groups.ResultsA significant reduction in fractional anisotropy values was shown for patients (mean ± SD: 0.37 ± 0.02) vs. controls (0.39 ± 0.03) regarding fibers between the left‐sided MFG and the putamen (p < 0.05). The same applied for linear anisotropy values in this connection (p < 0.05).ConclusionsOur results suggest an impaired structural connectivity between the left‐hemispheric MFG and putamen with a loss of equally aligned fibers in WC patients. This could reflect a structural basis for functional findings interpreted as altered inhibition and plasticity, both within the premotor cortex and the basal ganglia, that at last lead to the clinical symptoms of WC.

The impact of localized grey matter damage on neighboring connectivity: posterior cortical atrophy and the visual network.

Posterior cortical atrophy (PCA), a localized neurodegenerative syndrome involving the occipito-parietal cortices, can serve as a good model to elaborate on the consequence of a localized damage on the anatomical and functional connectivity within an affected system. Ten PCA patients and 14 aged-matched controls were enrolled. Structural connectivity was measured via Diffusion Tensor Imaging (DTI) and probabilistic tractography. The optic tracts and radiations and the splenial fibers were delineated and their microstructural properties were evaluated. Functional connectivity was measured by resting state functional MRI (rsfMRI). Voxel-based morphometry (VBM) was used to assess atrophy. Dorsal stream visual functions were tested and correlation between these behavioral data, volume measures, white matter integrity and connectivity were examined. Impaired white matter integrity was evident in patients' optic radiations and occipito-callosal fibers, in the segments located in close proximity to the occipital cortex, suggesting a localized damage. Degeneration did not proceed to the optic tracts, opposing trans-synaptic changes. rsfMRI revealed reduced connectivity within the visual network and between the visual and other related areas such as the frontal eye field. Correlations were found between grey matter volume and spatial perception abilities and between the integrity of the affected fibers and motion perception. White matter involvement in PCA seems to be grey matter dependent. Functional connectivity, on the other hand, showed a more diffuse pattern of damage. Correlations were found between the integrity of the affected fibers and patients' visual abilities suggesting that fiber integrity plays a role in determining behavioral manifestation.

Association of excessive social media use with abnormal white matter integrity of the corpus callosum

Borrowing from findings regarding other problematic behaviors, we posit that excessive social media use (ESMU) can relate to impaired inter-hemispheric connections. These are often reflected in impaired white matter integrity (decreased fractional anisotropy and increased mean diffusivity) of the corpus callosum. We test this idea with diffusion tensor imaging (DTI) data from 20 normal social media users with varying degrees of ESMU. The findings of a Regions of Interest analysis focusing on the corpus callosum indicate that ESMU is associated with increased mean diffusivity in the body and splenium sub-regions of the corpus callosum. Whole-brain Tract Based Spatial Statistics analysis revealed that ESMU is positively associated with mean diffusivity of left superior and inferior longitudinal fasciculi as well as left forceps minor; and that ESMU is positively associated with the fractional anisotropy of the right Corticospinal Tract. It is concluded that inter-hemispheric white matter deficits in the corpus callosum extended to forceps minor, as well as along the ventral semantic path can be associated with ESMU.

Association between abnormal serum myelin-specific protein levels and white matter integrity in first-episode and drug-naïve patients with major depressive disorder

BackgroundAlthough the structural abnormalities of white matter (WM) have been described in patients with major depressive disorder (MDD), the neuropathological changes remain unclear. The current study aimed to investigate the myelin oligodendrocyte glycoprotein (MOG) and myelin-associated glycoprotein (MAG) levels and their correlations with WM integrity in first-episode, drug-naïve MDD patients. MethodsWe obtained diffusion tensor images of 102 first-episode, drug-naïve MDD patients and 81 age- and sex-matched controls. Serum MOG and MAG levels of all participants were measured and compared between the two groups. The correlations between WM integrity and MOG and MAG levels were examined. ResultsMOG and MAG serum levels were significantly higher in MDD patients than in controls. Patients with MDD also showed decreased fractional anisotropy (FA) and axial diffusivity in the WM of the bilateral thalamus, right hippocampus, right temporal lobe, and left pulvinar. At the whole-brain level, no regions showed any correlations of diffusivity parameters with MOG or MAG levels in healthy subjects. However, we observed two-way correlations between the MOG and MAG levels and the FA and mean diffusivity values in the WM of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in MDD patients. LimitationsFurther investigation with a larger sample size and longitudinal studies are required to better understand the neuropathology of WM integrity in MDD. ConclusionsOur findings represent the first evidence of a relationship between abnormal serum myelin-specific protein levels and impaired WM integrity, which may help to better understand the neurobiological mechanisms of MDD.

Abstract TMP27: Tgfalpha Protects Oligodendrocytes Against Ischemic Injury and Promotes White Matter Integrity After Stroke

Introduction: The loss of white matter integrity after ischemic stroke contributes to long-term sensorimotor and cognitive deficits. Elucidating the mechanisms for white matter protection or recovery is therefore important to improve stroke outcomes. This study investigates the function of TGFα, a member of the epidermal growth factor family, in white matter recovery after stroke and elucidate the mechanisms of action. Methods: Cerebral ischemia was induced by transient (60 min) middle cerebral artery occlusion (tMCAO) in wild type and TGFα knockout mice. The spatiotemporal pattern of TGFα expression was evaluated by immunofluorescent staining at 1, 3, 5, 14, 21 and 35 days after tMCAO. Sensorimotor (rota-rod test, adhesive-remove test and open field test) and cognitive (Morris water-maze test) functions were assessed up to 35 days after stroke. White matter injury was quantified by MBP (myelin basic protein) and SMI32 (recognizes damaged non-phosphorylated neurofilament proteins) staining. The direct effect of TGFα on oligodendrocytes were evaluated in vitro using primary cultures. Live/dead cell staining and LDH (lactate dehydrogenase) assay were used to assess oligodendrocytes death after 90 min oxygen and glucose deprivation (OGD). Result: Cerebral ischemic induced an abrupt and transient increase of TGFα in the brain. The expression of TGFα was mainly increased in microglia and neurons. TGFα deficiency resulted in exacerbation in sensorimotor and cognitive deficits up to 35 days after tMCAO. MAP2 (microtubule-associated protein 2) staining at 3 days and 35 days showed lager tissue loss in TGFα knockout mice as compared with wild type stroke mice. Importantly. TGFα knockout mice also exhibited impaired white matter integrity, as revealed by the loss of MBP staining and elevation in SMI32 staining, at 35 days after stroke. Correlation analysis demonstrated positive correlation between white matter integrity and functional outcomes after stroke in TGFα knockout mice and wild type mice. In vitro study confirmed that TGFα (5, 10 or 20 ng/ml) protected oligodendrocyte precursor cells and oligodendrocytes against OGD. Conclusion: TGFα is important for maintaining white matter integrity and improving neurological recovery after stroke.

Impaired long contact white matter fibers integrity is related to depression in Parkinson's disease.

Depression is one of the most common nonmotor symptoms in Parkinson's disease (PD). But the pathogenesis is still unclear. Studies have shown that depression in PD is closely related to the white matter abnormalities, but the number of studies is still very small and lack of whole brain white matter lesions study. In this study, we investigated whole brain white matter integrity in 31 depressed PD patients and 37 nondepressed PD patients by diffusion tensor imaging. There was no difference in age, gender, age of onset, disease duration, Hoehn-Yahr scale, Unified Parkinson's Disease Rating Scale scores-III, and Mini-Mental State Examination scores between the two groups. The only difference was the Hamilton Depression Rating Scale. Depressed PD patients showed reduced fractional anisotropy values in the left anterior corona radiata, left posterior thalamic radiation, left cingulum, left superior longitudinal fasciculus, left sagittal stratum (including inferior longitudinal fasciculus and inferior fronto-occipital fasciculus), and left uncinate fasciculus. In patients with depression, the Hamilton Depression Rating Scale (HDRS) was negatively correlated with the FA value in the left cingulum (r=-0.712, P=.032) and left superior longitudinal fasciculus (r=-0.699, P=.025). This study suggested depression in PD was related to impaired white matter integrity especially the long contact fibers in the left hemisphere. These findings may be helpful for further understanding the potential mechanisms underlying depression in PD.

Association of obesity with cognitive function and brain structure in patients with major depressive disorder

BackgroundObesity has been implicated in the pathophysiology of major depressive disorder (MDD), which prompted us to examine the possible association of obesity with cognitive function and brain structure in patients with MDD. MethodsThree hundred and seven patients with MDD and 294 healthy participants, matched for age, sex, ethnicity (Japanese), and handedness (right) were recruited for the study. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Gray and white matter structures were analyzed using voxel-based morphometry and diffusion tensor imaging in a subsample of patients (n = 114) whose magnetic resonance imaging (MRI) data were obtained using a 1.5 T MRI system. ResultsVerbal memory, working memory, motor speed, attention, executive function, and BACS composite scores were lower for the MDD patients than for the healthy participants (p < 0.05). Among the patient group, working memory, motor speed, executive function, and BACS composite scores were lower in obese patients (body mass index ≥ 30, n = 17) than in non-obese patients (n = 290, p < 0.05, corrected). MRI determined frontal, temporal, thalamic, and hippocampal volumes, and white matter fractional anisotropy values in the internal capsule and left optic radiation were reduced in obese patients (n = 7) compared with non-obese patients (n = 107, p < 0.05, corrected). LimitationsSample size for obese population was not very large. ConclusionsObesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size-signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.

Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional “disconnection” in PD needs further characterization.We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow.PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls.Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.

Beyond the Arcuate Fasciculus: Damage to Ventral and Dorsal Language Pathways in Aphasia.

Previous regional-based diffusion tensor imaging (DTI) studies focused on impairment of the arcuate fasciculus in aphasia; little is known about the extent to which aphasia severity is affected by damage to both ventral and dorsal language white matter (WM) pathways. To understand whether disconnection of these pathways contributes to clinical symptoms, we assessed the relationship between the alterations of WM integrity and clinical characteristics in acute aphasia after stroke. Eighteen patients with acute aphasia and age-, gender-, and education-matched healthy controls underwent language assessment and DTI scanning. The whole brain unbiased tract-based spatial statistics method was employed to quantitate WM integrity (fractional anisotropy) for both groups. Linear correlation analyses were performed to evaluate the relationship between WM integrity and clinical features. The aphasic patients showed decreased WM integrity in the left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus (IFOF/ILF) and the left uncinate fasciculus, which represents components of ventral language pathway, and the left superior longitudinal fasciculus (SLF), which relates to dorsal language pathway. In addition, WM integrity of the left IFOF and SLF showed a positive correlation with aphasia quotient, performance quotient, and cortical quotient, respectively. These findings suggested that impaired WM integrity in both language pathways not only contributed to language performance, but also to general cognitive status. We suggest that aphasia involves a breakdown of multiple connections of dorsal and ventral streams that directly contributes to language deficits. Damage to these dual-streams may serve as a neuromarker for aphasias after stroke.

Spatiotemporal changes in diffusion, T2 and susceptibility of white matter following mild traumatic brain injury.

Impaired white matter integrity in traumatic brain injury (TBI) can lead to deficits in various neurological functions. The differentiation of the underlying pathological processes, e.g. edema, demyelination, axonal damage, to name a few, is of key clinical interest for the assessment of white matter injury. In this study, a combination of T2 , diffusion and susceptibility MRI was used to study the spatiotemporal changes in white matter at 1 h, 3 h, and 1, 2, 7 and 14 days following TBI, using a rat controlled cortical impact (CCI) model. Based on radial diffusivity (RD), the rats were divided into two groups: group 1 showed widespread increases in RD along the corpus callosum of the ipsilesional hemisphere at day 2, and group 2 showed normal RD. Based on this group separation, group 1 also showed similar widespread changes in fractional anisotropy (FA) and T2 at day 2, and group 2 showed normal FA and T2 . The widespread changes in RD and T2 in group 1 on day 2 were apparently dominated by edema, which obscured possible myelin and axonal damage. In contrast, the susceptibility of group 1 showed more localized increases near the impact site on day 2, and otherwise similar contrast to the contralesional hemisphere. The localized susceptibility increase is probably a result of demyelination and axonal injury. The extent of brain damage between the two groups revealed by MRI was consistent with behavioral results, with the first group showing significantly increased forelimb asymmetry and increased forelimb foot fault deficits. Our results suggest that the combination of T2 , diffusion and susceptibility MRI may provide an opportunity for the differential assessment of edema and axonal damage in TBI. Copyright © 2016 John Wiley & Sons, Ltd.

Interictal serum brain-derived neurotrophic factor level reflects white matter integrity, epilepsy severity, and cognitive dysfunction in chronic temporal lobe epilepsy.

Most patients with temporal lobe epilepsy (TLE) have epileptic foci originating from the medial temporal lobe, particularly the hippocampus. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor mainly expressed in the hippocampus, though it is not known whether the circulating level of BDNF reflects cognitive performance or white matter structural changes in chronic TLE. Thirty-four patients with TLE and 22 healthy controls were enrolled for standardized cognitive tests, diffusion tensor imaging, and serum BDNF measurement. The patients were further divided into a subgroup with unilateral TLE (n=23) and a subgroup with bilateral TLE (n=11) for clinical and neuroimaging comparisons. There were significantly lower BDNF levels in the patients with TLE compared with the controls, with significance contributed mainly from the subgroup with bilateral TLE, which also had more frequent seizures. The BDNF levels correlated with epilepsy duration (σ=-0.355; p=0.040) and fractional anisotropy (FA) in the left temporal lobe, left thalamus, and right hippocampus. Using a regression model, BDNF level predicted verbal memory score. Further, design fluency scores were predicted by serum BDNF level via the interactions with left temporal FA. Serum BDNF levels reflected longer epilepsy duration, impaired white matter integrity, and poor cognitive function in patients with chronic TLE.

White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc.