White Matter Changes In Patients Research Articles

Probing diffusion of water and metabolites to assess white matter microstructure in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder caused by the absence of functional dystrophin protein. In addition to muscle, dystrophin is expressed in the brain in both neurons and glial cells. Previous studies have shown altered white matter microstructure in patients with DMD using diffusion tensor imaging (DTI). However, DTI measures the diffusion properties of water, a ubiquitous molecule, making it difficult to unravel the underlying pathology. Diffusion-weighted spectroscopy (DWS) is a complementary technique which measures diffusion properties of cell-specific intracellular metabolites. Here we performed both DWS and DTI measurements to disentangle intra- and extracellular contributions to white matter changes in patients with DMD. Scans were conducted in patients with DMD (15.5 ± 4.6 y/o) and age- and sex-matched healthy controls (16.3 ± 3.3 y/o). DWS measurements were obtained in a volume of interest (VOI) positioned in the left parietal white matter. Apparent diffusion coefficients (ADCs) were calculated for total N-acetylaspartate (tNAA), choline compounds (tCho), and total creatine (tCr). The tNAA/tCr and tCho/tCr ratios were calculated from the non-diffusion-weighted spectrum. Mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and fractional anisotropy of water within the VOI were extracted from DTI measurements. DWS and DTI data from patients with DMD (respectively n= 20 and n= 18) and n= 10 healthy controls were included. No differences in metabolite ADC or in concentration ratios were found between patients with DMD and controls. In contrast, water diffusion (MD, t= -2.727, p= 0.011; RD, t= -2.720, p= 0.011; AD, t= -2.715, p= 0.012) within the VOI was significantly higher in patients compared with healthy controls. Taken together, our study illustrates the potential of combining DTI and DWS to gain a better understanding of microstructural changes and their association with disease mechanisms in a clinical setting.

Diabetes-related clinical and microstructural white matter changes in patients with Alzheimer's disease.

Although there exists substantial epidemiological evidence indicating an elevated risk of dementia in individuals with diabetes, our understanding of the neuropathological underpinnings of the association between Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) remains unclear. This study aims to unveil the microstructural brain changes associated with T2DM in AD and identify the clinical variables contributing to these changes. In this retrospective study involving 64 patients with AD, 31 individuals had concurrent T2DM. The study involved a comparative analysis of diffusion tensor imaging (DTI) images and clinical features between patients with and without T2DM. The FSL FMRIB software library was used for comprehensive preprocessing and tractography analysis of DTI data. After eddy current correction, the "bedpost" model was utilized to model diffusion parameters. Linear regression analysis with a stepwise method was used to predict the clinical variables that could lead to microstructural white matter changes. We observed a significant impairment in the left superior longitudinal fasciculus (SLF) among patients with AD who also had T2DM. This impairment in patients with AD and T2DM was associated with an elevation in creatine levels. The white matter microstructure in the left SLF appears to be sensitive to the impairment of kidney function associated with T2DM in patients with AD. The emergence of AD in association with T2DM may be driven by mechanisms distinct from the typical AD pathology. Compromised renal function in AD could potentially contribute to impaired white matter integrity.

Diffusion tensor imaging in photosensitive and nonphotosensitive juvenile myoclonic epilepsy

Introduction/backgroundJuvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. MethodsThis study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. ResultsIn the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. ConclusionsOur results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.

Effect of HD-tDCS on white matter integrity and associated cognitive function in chronic schizophrenia: A double-blind, sham-controlled randomized trial

Schizophrenia is a disabling major mental disorder, which includes critical deficits in cognitive function, for which no effective intervention currently exists. The aim of our double-blind, randomized, sham-controlled trial was to evaluate the effects of high-definition transcranial direct current stimulation (HD-tDCS) on the cognitive deficits in schizophrenia. This study sample consisted of 56 individuals with chronic schizophrenia, randomly allocated to either the active stimulation or sham group. The treatment consisted of ten consecutive days of HD-tDCS, 20 min/day, applied over the left dorsolateral prefrontal lobe. Changes in clinical outcomes, cognitive assessments, and diffusion tensor imaging were evaluated pre- to post-intervention. Matched-healthy controls (HCs) were included to identify white matter changes in patients with schizophrenia before treatment. Compared to HCs, schizophrenia was associated with reduced integrity of the white matter tracts of the corpus callosum and corona radiata. HD-tDCS enhanced integrity in the corpus callosum and anterior and superior corona radiata, which was associated with the change in cognitive performance. HD-tDCS offers a potential approach to improve cognition deficits in schizophrenia through a modulatory effect on white matter tracts. Given the lack of approved treatments for cognitive deficits, these findings are clinically relevant.

Disease-associated oligodendrocyte signatures in neurodegenerative disease: the known and unknown.

Disease-associated oligodendrocyte signatures in neurodegenerative disease: the known and unknown.

Divergent white matter changes in patients with nasopharyngeal carcinoma post-radiotherapy with different outcomes: a potential biomarker for prediction of radiation necrosis.

To investigate the effects of standard radiotherapy on temporal white matter (WM) and its relationship with radiation necrosis (RN) in patients with nasopharyngeal carcinoma (NPC), and to determine the predictive value of WM volume alterations at the early stage for RN occurrence at the late-delay stage. Seventy-four treatment-naive NPC patients treated with standard radiotherapy were longitudinally followed up for 36 months. Structural MRIs were collected at multiple time points during the first year post-radiotherapy. Longitudinal structural images were processed using FreeSurfer. Linear mixed models were used to delineate divergent trajectories of temporal WM changes between patients who developed RN and who did not. Four machine learning methods were used to construct predictive models for RN with temporal WM volume alterations at early-stage. The superior temporal gyrus (STG) had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. Patients with RN showed more rapid atrophy than those with NRN. A predictive model constructed with temporal WM volume alterations at early-stage post-radiotherapy had good performance for RN; the areas under the curve (AUC) were 0.879 and 0.806 at 1-3 months and 6 months post-radiotherapy, respectively. Moreover, the predictive model constructed with absolute temporal volume at 1-3 months post-radiotherapy also presented good performance; the AUC was 0.842, which was verified by another independent dataset (AUC = 0.773). NPC patients with RN had more sharp atrophy in the STG than those with NRN. Temporal WM volume at early-stage post-radiotherapy may serve as an in vivo biomarker to identify and predict RN occurrence. • The STG had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. • Although both groups exhibited time-dependent atrophy in the STG, the patients with RN showed a more rapid volume decrease than those with NRN. • Temporal WM volume alteration (or absolute volume) at the early stage could predict RN occurrence at the late-delay stage after radiotherapy.

White Matter Alterations in Depressive Disorder.

Depressive disorder is the most prevalent affective disorder today. Depressive disorder has been linked to changes in the white matter. White matter changes in depressive disorder could be a result of impaired cerebral blood flow (CBF) and CBF self-regulation, impaired blood-brain barrier function, inflammatory factors, genes and environmental factors. Additionally, white matter changes in patients with depression are associated with clinical variables such as differential diagnosis, severity, treatment effect, and efficacy assessment. This review discusses the characteristics, possible mechanisms, clinical relevance, and potential treatment of white matter alterations caused by depressive disorders.

Molecular biomarkers correlate with brain grey and white matter changes in patients with mitochondrial m.3243A > G mutation

IntroductionThe mitochondrial DNA (mtDNA) m.3243A > G mutation in the MT-TL1 gene results in a multi-systemic disease, that is commonly associated with neurodegenerative changes in the brain. MethodsSeventeen patients harboring the m3243A > G mutation were enrolled (age 43.1 ± 11.4 years, 10 M/7F). A panel of plasma biomarkers including lactate acid, alanine, L-arginine, fibroblast growth factor 21 (FGF-21), growth/differentiation factor 15 (GDF-15) and circulating cell free -mtDNA (ccf-mtDNA), as well as blood, urine and muscle mtDNA heteroplasmy were evaluated.Patients also underwent a brain standardized MR protocol that included volumetric T1-weighted images and diffusion-weighted MRI. Twenty sex- and age-matched healthy controls were included. Voxel-wise analysis was performed on T1-weighted and diffusion imaging, respectively with VBM (voxel-based morphometry) and TBSS (Tract-based Spatial Statistics). Ventricular lactate was also evaluated by 1H-MR spectroscopy. ResultsA widespread cortical gray matter (GM) loss was observed, more severe (p < 0.001) in the bilateral calcarine, insular, frontal and parietal cortex, along with infratentorial cerebellar cortex.High urine mtDNA mutation load, high levels of plasma lactate and alanine, low levels of plasma arginine, high levels of serum FGF-21 and ventricular lactate accumulation significantly (p < 0.05) correlated with the reduced brain GM density.Widespread microstructural alterations were highlighted in the white matter, significantly (p < 0.05) correlated with plasma alanine and arginine levels, with mtDNA mutation load in urine, with high level of serum GDF-15 and with high content of plasma ccf-mtDNA. ConclusionsOur results suggest that the synergy of two pathogenic mechanisms, mtDNA-related mitochondrial respiratory deficiency and defective nitric oxide metabolism, contributes to the brain neurodegeneration in m.3243A > G patients.

White matter tract-specific alterations in patients with primary restless legs syndrome

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients’ attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.

White matter integrity of watershed areas is potentially influenced by hypoperfusion in the presence permanent atrial fibrillation

Aim. To test a hypothesis of hypoperfusion-induced white matter changes in patients with atrial fibrillation (AFib) and to present statistics to compute sample size for the upcoming studies.Material and methods. We included 30 inpatients with AFib and investigated them with magnetic resonance imaging (MRI) with standard sequencies and diffusion tensor imaging (DTI). DTI data were analyzed with conventional ROI analysis in the Olea Sphere software and with watershed areas (WSA) mask in the FSL toolbox after nonlinear transformation of images to the Montreal Neurological Institute (MNI) space. Wilcoxon test was used to compare diffusion characteristics across subgroups.Results. Median age of participants was 73 years (69-78), 18 (60%) patients had moderate signs of small vessel disease with Fazekas score of one. Twenty-one patients had paroxysmal AFib. Analysis of WSA revealed decreased white matter integrity in the parieto-occipital cortical WSA with a pattern of significantly increased mean diffusivity (p=0,039), and marginally significant decrease in fractional anisotropy (p=0,056). Rank-based effect size across areas under comparison was either small (0,2) or negligible, and with statistical power in the range of 0,05-1.Conclusion. Atrial fibrillation could have pathophysiologically feasible mechanism to affect white matter integrity in the watershed areas.

24234 Development of a computerized neurocognitive test of interhemispheric transfer for use in pediatric settings

ABSTRACT IMPACT: As newborn screening is now available for X-linked adrenoleukodystrophy, there is a need to establish meaningful disease markers to detect the onset of the severe demyelinating cerebral form of this disease at the earliest possible stage, and to quantify early disease progression to evaluate the relative efficacy of therapies. OBJECTIVES/GOALS: Longitudinal testing of neurocognitive and motor function using smartphone and tablet-based applications holds promise for early detection and quantification of brain white matter changes in patients with adrenoleukodystrophy (ALD) and other rare demyelinating diseases, but this methodology requires validation in pediatric populations. METHODS/STUDY POPULATION: We developed an iPad application with a game-like interface to assess interhemispheric transfer across the corpus callosum, the brain structure where cerebral demyelinating disease typically begins in patients with ALD. Feasibility data from remote test administrations with healthy children were collected to analyze and speed and timing of finger tapping movements requiring bimanual coordination on a touchscreen. RESULTS/ANTICIPATED RESULTS: Among our pilot sample of healthy school-aged children, age-related improvements in finger tapping speed were observed in both single-hand and alternating-hand conditions. Results indicate that remote testing using iPad applications is a viable way to collect psychometric testing data rapidly in pediatric populations and is feasible during a pandemic. Next steps in this research project will be: (1) evaluating the stability of repeated test administrations (test-retest reliability), (2) assessing agreement between performance on our iPad application and validated measures of interhemispheric transfer and fine motor function, and (3) comparing performance of children with known corpus callosum white matter abnormality to performance of healthy children. DISCUSSION/SIGNIFICANCE OF FINDINGS: Brief neurocognitive tests that can be frequently administered may have the ability to capture subtle brain changes in developing children. Approaches enabling remote (virtual) testing will facilitate research during the covid-19 pandemic and are especially well-suited for data collection in rare disease populations.

Visual Dysfunction Predicts Cognitive Impairment and White Matter Degeneration in Parkinson's Disease.

ABSTRACTBackgroundVisual dysfunction predicts dementia in Parkinson's disease (PD), but whether this translates to structural change is not known. The objectives of this study were to identify longitudinal white matter changes in patients with Parkinson's disease and low visual function and also in those who developed mild cognitive impairment.MethodsWe used fixel‐based analysis to examine longitudinal white matter change in PD. Diffusion MRI and clinical assessments were performed in 77 patients at baseline (22 low visual function/55 intact vision and 13 PD‐mild cognitive impairment/51 normal cognition) and 25 controls and again after 18 months. We compared microstructural changes in fiber density, macrostructural changes in fiber bundle cross‐section and combined fiber density and cross‐section, across white matter, adjusting for age, sex, and intracranial volume.ResultsPatients with PD and visual dysfunction showed worse cognitive performance at follow‐up and were more likely to develop mild cognitive impairment compared with those with normal vision (P = 0.008). Parkinson's with poor visual function showed diffuse microstructural and macrostructural changes at baseline, whereas those with mild cognitive impairment showed fewer baseline changes. At follow‐up, Parkinson's with low visual function showed widespread macrostructural changes, involving the fronto‐occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in those with mild cognitive impairment at baseline or converters, even when the 2 groups were combined.ConclusionParkinson's patients with poor visual function show increased white matter damage over time, providing further evidence for visual function as a marker of imminent cognitive decline. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association between microstructural white matter abnormalities and cognitive functioning in patients with type 2 diabetes mellitus: a diffusion tensor imaging study

BackgroundDiffusion tensor imaging (DTI) technique is important for exploring more sensitive imaging-based biomarkers in prevention and early treatment of cognitive dysfunction induced by type 2 diabetes mellitus (DM).ObjectivesTo predict early cognitive dysfunction and detection of microstructural white matter changes in patients with type 2 DM by diffusion tensor imaging.Patients and methodsA case-control study included thirty patients aged ≥ 18 years old of both sexes with type 2 DM and 30 controls. All subjects underwent to Montreal Cognitive Assessment (MoCA) “Arabic version”: to detect mild cognitive impairment (MCI) and diffusion tensor imaging study (DTI).ResultsMild cognitive impairment is related to type 2 DM (56.7% of diabetic group), reduced fractional anisotropy (FA) values, and elevated mean diffusivity (MD) values were related to cognitive impairment evaluated through Montreal Cognitive Assessment (MoCA) in patients with type 2 DM.ConclusionThe integrity of the white matter measured using DTI vary in MCI diabetics compared with non-MCI diabetics. Such changes have major implications on the cognitive function.

Normal Pressure Hydrocephalus: Clinical Symptoms, Cerebrospinal Fluid Flow Metrics and White Matter Changes.

The aim of this study was to investigate correlations between clinical symptoms, cerebrospinal fluid flow metrics, hydrocephalus index, small-vessel disease, and white matter (WM) changes in normal pressure hydrocephalus (NPH). Aquaductal stroke volumes (ASVs), Z Evans index, Fazekas grading (FG), and diffusion tensor imaging measurements from WM bundles of 37 patients with NPH were retrospectively evaluated. Mann-Whitney U test between clinical symptoms and other variables and Spearman ρ correlations for relationships between variables and Kruskal-Wallis to correlate FG with nonclinical variables were used. Patients with NPH had increased ASV (median 53 μL). No correlation was found between Z Evans index and ASV. Three groups of patients with dementia or ataxia or incontinence had increased ASV values than their counterparts without symptoms (55 vs 48.5 μL, 75 vs 47 μL, 64 vs 49.5 μL, respectively). Patients having 2 common symptoms of dementia and ataxia and patients having all 3 symptoms of dementia, ataxia, and incontinence were compared with ASV values of 63.5 versus 78 μL, respectively. Patients with FG 1 had median ASV values of 45 μL; FG 2, 82.5 μL; and FG 3, 59 μL. Patients with dementia had significantly higher apparent diffusion coefficient (ADC) values of corona radiata (CR) on both sides. There were no significant WM changes in patients with ataxia and incontinence. The Z Evans index was positively correlated with ADC values of CR on both sides and genu of corpus callosum. Fazekas grading was found positively correlated with ADC and negatively correlated with FA values of CR. Patients with NPH, regardless of stages of the diseases, have increased ASV values and could benefit from shunting. Decreasing ASV values of patients with FG 3 comparing with those with FG 2 support the hypothesis of decreasing compliance of brain with aging and increasing severity of small-vessel disease.

Evaluation of white matter microstructure in patients with Parkinson's disease using microscopic fractional anisotropy.

Micro fractional anisotropy (μFA) is more accurate than conventional fractional anisotropy (FA) for assessing microscopic tissue properties and can overcome limitations related to crossing white matter fibres. We compared μFA and FA for evaluating white matter changes in patients with Parkinson's disease (PD). We compared FA and μFA measures between 25 patients with PD and 25 age- and gender-matched healthy controls using tract-based spatial statistics (TBSS) analysis. We also examined potential correlations between changes, revealed by conventional FA or μFA, and disease duration or Unified Parkinson's Disease Rating Scale (UPDRS)-III scores. Compared with healthy controls, patients with PD had significantly reduced μFA values, mainly in the anterior corona radiata (ACR). In the PD group, μFA values (primarily those from the ACR) were significantly negatively correlated with UPDRS-III motor scores. No significant changes or correlations with disease duration or UPDRS-III scores with tissue properties were detected using conventional FA. μFA can evaluate microstructural changes that occur during white matter degeneration in patients with PD and may overcome a key limitation of FA.

Age- and disease-related cerebral white matter changes in patients with Parkinson's disease

As age and Parkinson's disease (PD) both play a role in the degeneration of brain white matter, we aimed to investigate a possible interaction effect of age and disease presence on white matter integrity in patients with PD. We studied white matter hyperintensity volume, global fractional anisotropy, mean diffusivity and mean magnetization transfer ratio of normal appearing white matter in 163 patients with PD and 218 age- and gender-matched healthy control subjects. We investigated the relationship between age and these parameters in both groups, and interaction between age and disease presence. Patients with PD had a higher load of white matter hyperintensities with a preferential periventricular and anterior distribution as compared with healthy control subjects. Visuospatial functioning was related to total and postural instability and gait difficulty was related to periventricular white matter hyperintensity volume in patients with PD. The age-related decline of white matter integrity was similar for both groups. Global microstructural integrity of the normal appearing white matter did not differ between patients and healthy control subjects, suggesting that PD-specific changes do not exceed normal age-associated change in white matter without lesions.

Impaired illness awareness in schizophrenia and posterior corpus callosal white matter tract integrity

Impaired illness awareness (Imp-IA) in schizophrenia is associated with interhemispheric imbalance, resulting in left hemisphere dominance, primarily within the posterior parietal area (PPA). This may represent an interhemispheric “disconnection syndrome” between PPAs. To test this hypothesis, we aimed to determine if diffusion-based measures of white matter integrity were disrupted in the corpus callosal tracts linking PPAs (i.e., splenium) in patients with Imp-IA in schizophrenia. T1-weighted and diffusion-weighted scans were acquired on a 1.5T GE scanner for 100 participants with a DSM-IV-TR diagnosis of schizophrenia and 134 healthy controls aged 18 to 79 years. The corpus callosal white matter tracts were compared among patients with Imp-IA (n = 40), intact illness awareness (n = 60), and healthy controls. White matter disruption was measured with fractional anisotropy (FA) and mean diffusivity (MD). Group differences in FA were found in the splenium, with patients with Imp-IA having the lowest FA, which remained significant after controlling for sex, age, global cognition, and premorbid intelligence. No group differences in MD were observed. Splenial white matter tracts of the corpus callosum appear compromised in patients with Imp-IA. Transcallosal interhemispheric PPA white matter disruption may represent a “disconnection syndrome”, manifesting as Imp-IA in schizophrenia. Future studies are required to investigate the effects of noninvasive brain stimulation interventions, such as transcranial direct current or magnetic stimulation, on Imp-IA in association with white matter changes in patients with schizophrenia.

White Matter Changes in Patients with Alzheimer’s Disease and Associated Factors

Alzheimer’s disease (AD) is traditionally thought of as a neurodegenerative disease. Recent evidence shows that beta amyloid-independent vascular changes and beta amyloid-dependent neuronal dysfunction both equally influence the disease, leading to loss of structural and functional connectivity. White matter changes (WMCs) in the brain are commonly observed in dementia patients. The effect of vascular factors on WMCs and the relationship between WMCs and severity of AD in patients remain to be clarified. We recruited 501 clinically diagnosed probable AD patients with a series of comprehensive neuropsychological tests and brain imaging. The WMCs in cerebral CT or MRI were rated using both the modified Fazekas scale and the combined CT-MRI age related WMC (ARWMC) rating scale. Periventricular WMCs were observed in 79.4% of the patients and deep WMCs were also seen in 48.7% of the patients. WMC scores were significantly higher in the advanced dementia stage in periventricular WMCs (p = 0.001) and total ARWMCs (p < 0.001). Age and disease severity were both independently associated with WMCs score, particularly in the total, frontal and parieto-occipital areas. Vascular factors including hypertension, diabetes mellitus, and gender were not significantly associated with WMCs. In conclusion, both age and severity of dementia were significantly associated with WMCs in AD patients. These associations highlight future research targets.

Childhood trauma- and cannabis-associated microstructural white matter changes in patients with psychotic disorder: a longitudinal family-based diffusion imaging study.

Decreased white matter (WM) integrity in patients with psychotic disorder has been a consistent finding in diffusion tensor imaging (DTI) studies. However, the contribution of environmental risk factors to these WM alterations is rarely investigated. The current study examines whether individuals with (increased risk for) psychotic disorder will show increased WM integrity change over time with increasing levels of childhood trauma and cannabis exposure. DTI scans were obtained from 85 patients with a psychotic disorder, 93 non-psychotic siblings and 80 healthy controls, of which 60% were rescanned 3 years later. In a whole-brain voxel-based analysis, associations between change in fractional anisotropy (ΔFA) and environmental exposures as well as interactions between group and environmental exposure in the model of FA and ΔFA were investigated. Analyses were adjusted for a priori hypothesized confounding variables: age, sex, and level of education. At baseline, no significant associations were found between FA and both environmental risk factors. At follow-up as well as over a 3-year interval, significant interactions between group and, respectively, cannabis exposure and childhood trauma exposure in the model of FA and ΔFA were found. Patients showed more FA decrease over time compared with both controls and siblings when exposed to higher levels of cannabis or childhood trauma. Higher levels of cannabis or childhood trauma may compromise connectivity over the course of the illness in patients, but not in individuals at low or higher than average genetic risk for psychotic disorder, suggesting interactions between the environment and illness-related factors.

Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 2: Effect on White Matter Integrity

Background. Constraint-induced movement therapy (CIMT) is a method of physical rehabilitation that has demonstrated clinical efficacy in patients with chronic stroke, cerebral palsy, and multiple sclerosis (MS). Objective. This pilot randomized controlled trial tested whether CIMT can also induce increases in white matter integrity in patients with MS. Methods. Twenty adults with chronic hemiparetic MS were randomized to receive either CIMT or complementary and alternative medicine (CAM) treatment (reported in the first article of this pair). Structural white matter change was assessed by tract-based spatial statistics (TBSS); measures included fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Results. CIMT and CAM groups did not differ in pretreatment disability or expectancy to benefit. As noted in the companion paper, the motor activity log (MAL) improved more after CIMT than CAM (P < .001); the within-group effect size for CIMT was 3.7 (large d′ = 0.57), while for CAM it was just 0.7. Improvements in white matter integrity followed CIMT and were observed in the contralateral corpus callosum (FA, P < .05), ipsilateral superior occipital gyrus (AD, P < .05), ipsilateral superior temporal gyrus (FA, P < .05), and contralateral corticospinal tract (MD and RD, P < .05). Conclusion. CIMT produced a very large improvement in real-world limb use and induced white matter changes in patients with hemiparetic MS when compared with CAM. The findings suggest in preliminary fashion that the adverse changes in white matter integrity induced by MS might be reversed by CIMT. Clinical trial registration number: ClinicalTrials.gov (NCT01081275)