Voxelwise Diffusion Tensor Imaging Research Articles

The effects of physical activity on white matter microstructure in children with overweight or obesity: The ActiveBrains randomized clinical trial

BackgroundEmerging research supports the idea that physical activity benefits brain development. However, the body of evidence focused on understanding the effects of physical activity on white matter microstructure during childhood is still in its infancy, and further well-designed randomized clinical trials are needed. AimThis study aimed: (i) to investigate the effects of a 20-week physical activity intervention on global white matter microstructure in children with overweight or obesity, and (ii) to explore whether the effect of physical activity on white matter microstructure is global or restricted to a particular set of white matter bundles. MethodsIn total, 109 children aged 8 to 11 years with overweight or obesity were randomized and allocated to either the physical activity program or the control group. Data were collected from November 2014 to June 2016, with diffusion tensor imaging (DTI) data processing and analyses conducted between June 2017 and November 2021. Images were pre-processed using the Functional Magnetic Resonance Imaging (MRI) of the Brain´s Software Library (FSL) and white matter properties were explored by probabilistic fiber tractography and tract-based spatial statistics (TBSS). ResultsIntention-to-treat analyses were performed for all children who completed the pre-test and post-test DTI assessment, with good quality DTI data (N = 89). Of them, 83 children (10.06±1.11 years, 39 % girls, intervention group=44) met the per-protocol criteria (attended at least 70 % of the recommended sessions). Our probabilistic fiber tractography analysis did not show any effects in terms of global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in the per-protocol or intention-to-treat analyses. Additionally, we did not observe any effects on the voxel-wise DTI parameters (i.e., FA and MD) using the most restricted TBSS approach (i.e., per protocol analyses and p-corrected image with a statistical threshold of p < 0.05). In the intention-to-treat analysis, we found that our physical activity program had a borderline effect (p-corrected image with a statistical threshold of p < 0.1) on 7 different clusters, including a cluster in the corpus callosum. ConclusionWe conclude that a 20-week physical activity intervention was not enough to induce changes in global and tract-specific white matter during childhood. The effects of physical activity on white matter microstructure could be restricted to local changes in several white matter tracts (e.g., the body of the corpus callosum). However, our results were not significant, and more interventions are needed to determine whether and how physical activity affects white matter microstructure during childhood.

Years of play alter MRI measures of brain health in former Canadian Football League athletes: a pilot study

Introduction: Concussive and sub-concussive blows are commonly sustained during contact sports. Through a detailed neuroimaging analysis, this pilot study aimed to determine if a history of sport-related concussions exacerbated cognitive decline later in life. It was hypothesized that clinical health assessments and magnetic resonance imaging (MRI) techniques would provide insight into lasting health and well-being, structural, microstructural, and functional alterations caused by a history of concussive injuries. Materials and Methods: Twenty aging, retired Canadian Football League (rCFL) players (aged 56.9 ± 6.9) had clinical testing and MRI data acquired. Cortical thickness, voxel-wise diffusion tensor imaging (DTI), and Default Mode Network (DMN) connectivity data was collected for each subject and compared against healthy controls. Retired athlete age, playing position, and career length were also examined. Results: This study found widespread cortical thinning, significantly increased mean diffusivity, increased axial diffusivity, and both hyperactivity and hypoactivity within the DMN. Athlete age, position, and career length all influenced microstructural integrity. On average, retired athletes scored about 4 times greater depression-like and concussion-related symptoms and scored significantly lower in all health categories compared to healthy controls. Conclusions: These findings suggested that lasting signs of neurological injuries were present years after retiring from professional play.

Structural connectivity and its association with social connectedness in early adolescence

Adolescence is a critical period of social and neural development. Brain regions which process social information develop throughout adolescence as young people learn to navigate social environments. Studies investigating brain structural connectivity (indexed by white matter (WM) integrity), and social connectedness in adolescents have been limited until recently, with literature stemming mostly from adult samples, broad age ranges within adolescence or based on social network characteristics as opposed to social connectedness. This cross-sectional study of 12-year-olds (N = 73) explored the relationship between social connectedness (SCS) and structural connectivity in early adolescence, to gauge how this snapshot of WM development is associated with social behaviour. Whole brain voxel-wise diffusion tensor imaging was undertaken to determine correlations between SCS and fractional anisotropy (FA), radial (RD) and axial (AD) diffusivity of clusters within WM tracts. Significant negative relationships between FA and SCS scores were found in clusters within 11 WM tracts, with significant positive correlations between SCS and both RD and AD across clusters within 13 and 8 clusters, respectively. Clusters within the genu of the corpus callosum (CCgn) showed strong correlations for all three metrics, and regression models that included gender, age, and psychological distress, revealed SCS to be the only significant predictor of CCgn FA, RD and AD values. Overall, these findings suggest that those with lower social connectedness had a WM profile suggestive of reduced axonal density and/or coherence. Longitudinal research is needed to track such WM profiles during adolescent development and determine the associations with mental health and well-being outcomes.

The regional relationship between CSF VEGF and white matter microstructural integrity in older adults: A voxelwise DTI study

AbstractBackgroundBoth white matter (WM) micro‐ and macro‐ structural abnormalities occur in Alzheimer’s disease (AD) with micro‐structural abnormalities likely preceding macrostructural changes in the AD cascade. Diffusion tensor imaging (DTI) fractional anisotropy (FA) ‐ which is sensitive to factors such as myelination, fiber coherence, and fiber density‐ within an MRI voxel may be used to detect AD‐specific deficits. However, mechanisms driving loss of WM microstructural integrity in AD are poorly understood. Vascular endothelial growth factor (VEGF) is a multi‐function vascular protein linked to early AD brain and cognition biomarkers. VEGF provides neurotrophic support via glia and is also secreted by glial cells essential for maintaining myelin. However, in humans, the relationship between VEGF and WM microstructural integrity has yet to be mapped. We evaluated whether cerebrospinal fluid (CSF) VEGF levels were associated with voxelwise WM FA in older adults without dementia.MethodWe evaluated 72 older adults without dementia from the USC Alzheimer’s Disease Research Center (ADRC) (mean age 65.7; 47‐82 years old) with a clinical dementia rating (CDR) score of 0 (n=56) or 0.5 (n=16) who had both CSF VEGF‐A levels and a 3 T diffusion MRI scan (64‐direction (b=1000 s/mm2) DWI volumes). MRI scans were pre‐processed to reduce artifacts related to motion, distortion, eddy currents, bias field, and susceptibility artifacts. Tract‐based spatial statistics, using FSL software, was implemented to derive skeletonized FA maps along WM tracts. The association between VEGF and voxelwise FA WM integrity was evaluated using FSL’s general linear model tool. We covaried for age, sex, and CDR. FA significance cluster maps were corrected for voxelwise multiple comparisons.ResultHigher CSF VEGF levels were associated with lower DTI FA, indicative of poorer WM microstructural integrity, in the left and right superior longitudinal fasciculus, left anterior thalamic radiation, and left inferior frontal occipital fasciculus (p&lt;0.05) (Figure 1).ConclusionThese results demonstrate for the first time in humans that VEGF levels are related to WM microstructure in older adults without dementia, primarily in long range association fibers connecting temporal, parietal, and frontal lobes. These pathways are essential for memory, language, attention and emotional control.

Alterations of cerebellar white matter integrity and associations with cognitive impairments in schizophrenia.

“Cognitive dysmetria” theory of schizophrenia (SZ) has highlighted that the cerebellum plays a critical role in understanding the pathogenesis and cognitive impairment in SZ. Despite some studies have reported the structural disruption of the cerebellum in SZ using whole brain approach, specific focus on the voxel-wise changes of cerebellar WM microstructure and its associations with cognition impairments in SZ were less investigated. To further explore the voxel-wise structural disruption of the cerebellum in SZ, the present study comprehensively examined volume and diffusion features of cerebellar white matter in SZ at the voxel level (42 SZ vs. 52 controls) and correlated the observed alterations with the cognitive impairments measured by MATRICS Consensus Cognitive Battery. Combing voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods, we found, compared to healthy controls (HCs), SZ patients did not show significant alteration in voxel-level cerebellar white matter (WM) volume and tract-wise and skeletonized DTI features. In voxel-wise DTI features of cerebellar peduncles, compared to HCs, SZ patients showed decreased fractional anisotropy and increased radial diffusivity mainly located in left middle cerebellar peduncles (MCP) and inferior cerebellar peduncles (ICP). Interestingly, these alterations were correlated with overall composite and different cognitive domain (including processing speed, working memory, and attention vigilance) in HCs but not in SZ patients. The present findings suggested that the voxel-wise WM integrity analysis might be a more sensitive way to investigate the cerebellar structural abnormalities in SZ patients. Correlation results suggested that inferior and MCP may be a crucial neurobiological substrate of cognition impairments in SZ, thus adding the evidence for taking the cerebellum as a novel therapeutic target for cognitive impairments in SZ patients.

Characteristics of White Matter Integrity During Different Phases of Abstinence in Heroin Use Disorders: A Diffusion Tensor Imaging Study.

The recovery of heroin-induced white matter impairment during abstinence has been reported, determining the characteristics of this recovery can help to improve the therapeutic strategies. In this study, we explored white matter characteristics in heroin use disorders during different phases of abstinence by using a quantitative diffusion tensor imaging method. Seventeen and 22 male patients with long- and short-term abstinence (LA and SA, respectively) from heroin use and 20 male healthy controls participated in this study. Voxel-wise diffusion tensor imaging method was used for the comparison of fractional anisotropy (FA). Radial diffusivity (RD) and axial diffusivity (AD) were induced to explore the pathological characteristics of FA. The correlation between diffusion tensor indices and duration of abstinence was further analyzed. Compared to the healthy controls, patients with SA had significantly reduced FA in extensive white matter regions, while those with LA had only 2 clusters that showed reduced FA, which were located mainly in the genu of the corpus callosum, forceps minor, uncinate fasciculus, left inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and posterior thalamic radiation. Significantly increased RD with unchanged axial diffusivity were detected. FA in the regions with the significant intergroup difference between SA and LA correlated positively with the duration of abstinence. The RD in these regions correlated negatively with the duration of abstinence. The findings suggested that the time-dependent recovery of white matter, especially the restoration of the myelin sheath, occurred in patients with LA. Longer-abstinent duration with strategies of enhancing myelination may improve treatment effectiveness.

Changes of Brain Structures and Psychological Characteristics in Predatory, Affective Violent and Nonviolent Offenders.

Purpose: Violent subjects were demonstrated to exhibit abnormal brain structures; however, the brain changes may be different between criminals committing affective (VA), predatory violence (VP), and non-violence (NV). Therefore, the purpose of this study was to compare the differences in brain structures and psychological characteristics between VA, VP, and NV offenders. Methods: Twenty male criminal subjects (7 VP; 6 VA; and 7 NV) offenders; and twenty age-matched male healthy non-criminals were enrolled in this study. All subjects received psychological assessments as well as magnetic resonance imaging scans of the brain. Analysis of variance (ANOVA) was performed to understand the differences among four groups with Bonferroni correction. The voxel-based morphometry and voxel-wise diffusion tensor imaging analyses were performed to compare the gray matter (GM) volume and white matter (WM) integrity between the groups. In significant regions, a Spearman correlation analysis was performed to understand the relationship between the brain changes and psychological scores. Results: The ANOVA analysis showed that AUDIT scores were significantly different among four groups, but no significant group difference was noted after Bonferroni correction. The imaging comparisons further demonstrated that the VP and NV offenders exhibited significant alterations of WM and GM tissues in the rectus and superior temporal gyrus, respectively. In addition, the VP offenders exhibited greater GM volumes than VA offenders in the right middle frontal gyrus, and NV offenders had greater GM volumes than VP offenders in the bilateral thalamus. Conclusion: We concluded that the VA, VP, and NV groups exhibited different degrees of alterations in GM and WM tissues in regions involved in emotion and cognition.

Gray and White Matter Changes Associated with Psychophysical Functions Induced by Diabolo Training in Young Men.

Learning a skill has been demonstrated to relate to neural plasticity in both animal and human brains. Performing diabolo consists of different tricks and may cause brain structural changes associated with psychophysical functions. Therefore, the purpose of this study was to investigate gray matter (GM) and white matter (WM) changes associated with psychophysical functions induced by diabolo training in healthy subjects. Fourteen healthy right-handed male subjects were enrolled to receive the diabolo training. Whole brain T1-weighted images and diffusion tensor imaging (DTI) data were acquired from all subjects on a 3.0 T magnetic resonance scanner before and after the training. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and voxel-wise DTI analysis were carried out to detect the GM volume, cortical thickness, and WM diffusion changes using T1-weighted image and DTI data, respectively. In addition, two-arm coordination and mirror-drawing tests were performed to evaluate their psychophysical functions before and after 2, 4, 6 and 8 weeks of training. Analysis of variance was performed to understand whether the psychophysical functions changed over time after the training. The results showed that the psychophysical functions were significantly changed over time during the training. The VBM and SBM analyses revealed that the GM volume and cortical thickness were significantly increased in the brain areas associated with visual, motor, sensory, and spatial cognition functions. The voxel-wise DTI analysis further demonstrated that the mean diffusivity was significantly reduced in the genu of corpus callosum. Moreover, significant correlations were revealed between the increase rate of GM volume and the improvement rate of psychophysical functions in the left angular gyrus. The results suggest that the diabolo training may induce increased GM volume associated with improved psychophysical function in the brain region involved in spatial cognition and attention. Therefore, we conclude that the diabolo training may improve psychophysical function which might be reflected by the increased GM volume in the angular gyrus.

Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer.

Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy. Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC - CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts. Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC - CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning. Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.

Functional and Structural Brain Damage in Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused by a GAA repeat expansion in the FXN gene. There is still no cure or quantitative biomarkers reliaby correlating with the progression rate and disease severity. Investigation of functional and structural alterations characterizing white (WM) and gray matter (GM) in FRDA are needed prerequisite to monitor progression and response to treatment. Here we report the results of a multimodal cross-sectional MRI study of FRDA including Voxel-Based Morphometry (VBM), diffusion-tensor imaging (DTI), functional MRI (fMRI), and a correlation analysis with clinical severity scores. Twenty-one early-onset FRDA patients and 18 age-matched healthy controls (HCs) were imaged at 3T. All patients underwent a complete cognitive and clinical assessment with ataxia scales. VBM analysis showed GM volume reduction in FRDA compared to HCs bilaterally in lobules V, VI, VIII (L>R), as well as in the crus of cerebellum, posterior lobe of the vermis, in the flocculi and in the left tonsil. Voxel-wise DTI analysis showed a diffuse fractional anisotropy reduction and mean, radial, axial (AD) diffusivity increase in both infratentorial and supratentorial WM. ROI-based analysis confirmed the results showing differences of the same DTI metrics in cortico-spinal-tracts, forceps major, corpus callosum, posterior thalamic radiations, cerebellar penduncles. Additionally, we observed increased AD in superior (SCP) and middle cerebellar peduncles. The WM findings correlated with age at onset (AAO), short-allelle GAA, and disease severity. The intragroup analysis of fMRI data from right-handed 14 FRDA and 15 HCs showed similar findings in both groups, including activation in M1, insula and superior cerebellar hemisphere (lobules V–VIII). Significant differences emerged only during the non-dominant hand movement, with HCs showing a stronger activation in the left superior cerebellar hemisphere compared to FRDA. Significant correlations were found between AAO and the fMRI activation in cerebellar anterior and posterior lobes, insula and temporal lobe. Our multimodal neuroimaging protocol suggests that MRI is a useful tool to document the extension of the neurological impairment in FRDA.

Association of White Matter Structure With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder

Clinical overlap between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasingly appreciated, but the underlying brain mechanisms remain unknown to date. To examine associations between white matter organization and 2 commonly co-occurring neurodevelopmental conditions, ASD and ADHD, through both categorical and dimensional approaches. This investigation was a cross-sectional diffusion tensor imaging (DTI) study at an outpatient academic clinical and research center, the Department of Child and Adolescent Psychiatry at New York University Langone Medical Center. Participants were children with ASD, children with ADHD, or typically developing children. Data collection was ongoing from December 2008 to October 2015. The primary measure was voxelwise fractional anisotropy (FA) analyzed via tract-based spatial statistics. Additional voxelwise DTI metrics included radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD), and mode of anisotropy (MA). This cross-sectional DTI study analyzed data from 174 children (age range, 6.0-12.9 years), selected from a larger sample after quality assurance to be group matched on age and sex. After quality control, the study analyzed data from 69 children with ASD (mean [SD] age, 8.9 [1.7] years; 62 male), 55 children with ADHD (mean [SD] age, 9.5 [1.5] years; 41 male), and 50 typically developing children (mean [SD] age, 9.4 [1.5] years; 38 male). Categorical analyses revealed a significant influence of ASD diagnosis on several DTI metrics (FA, MD, RD, and AD), primarily in the corpus callosum. For example, FA analyses identified a cluster of 4179 voxels (TFCE FEW corrected P < .05) in posterior portions of the corpus callosum. Dimensional analyses revealed associations between ASD severity and FA, RD, and MD in more extended portions of the corpus callosum and beyond (eg, corona radiata and inferior longitudinal fasciculus) across all individuals, regardless of diagnosis. For example, FA analyses revealed clusters overall encompassing 12121 voxels (TFCE FWE corrected P < .05) with a significant association with parent ratings in the social responsiveness scale. Similar results were evident using an independent measure of ASD traits (ie, children communication checklist, second edition). Total severity of ADHD-traits was not significantly related to DTI metrics but inattention scores were related to AD in corpus callosum in a cluster sized 716 voxels. All these findings were robust to algorithmic correction of motion artifacts with the DTIPrep software. Dimensional analyses provided a more complete picture of associations between ASD traits and inattention and indexes of white matter organization, particularly in the corpus callosum. This transdiagnostic approach can reveal dimensional relationships linking white matter structure to neurodevelopmental symptoms.

Functional networks and structural connectivity of visuospatial and visuoperceptual working memory.

Neural correlates of working memory (WM) in healthy subjects have been extensively investigated using functional MRI (fMRI). However it still remains unclear how cortical areas forming part of functional WM networks are also connected by white matter fiber bundles, and whether DTI measures, used as indices of microstructural properties and directionality of these connections, can predict individual differences in task performance. fMRI data were obtained from 23 healthy young subjects while performing one visuospatial (square location) and one visuoperceptual (face identification) 2-back task. Diffusion tensor imaging (DTI) data were also acquired. We used independent component analysis (ICA) of fMRI data to identify the main functional networks involved in WM tasks. Voxel-wise DTI analyses were performed to find correlations between structural white matter and task performance measures, and probabilistic tracking of DTI data was used to identify the white matter bundles connecting the nodes of the functional networks. We found that functional recruitment of the fusiform and the inferior frontal cortex was specific for the visuoperceptual working memory task, while there was a high overlap in brain activity maps in parietal and middle frontal areas for both tasks. Axial diffusivity and fractional anisotropy, of the tracts connecting the fusiform with the inferior frontal areas correlated with processing speed in the visuoperceptual working memory task. Although our findings need to be considered as exploratory, we conclude that both tasks share a highly-overlapping pattern of activity in areas of frontal and parietal lobes with the only differences in activation between tasks located in the fusiform and inferior frontal regions for the visuoperceptual task. Moreover, we have found that the DTI measures are predictive of the processing speed.

Diffusion tensor imaging detects microstructural reorganization in the brain associated with chronic irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurring abdominal pain associated with alterations in bowel habits. We hypothesized that patients with chronic visceral pain associated with IBS may have microstructural differences in the brain compared with healthy control subjects (HCs), indicative of long-term neural reorganization of chronic pain pathways and regions associated with sensory integration. In the current study we performed population-based voxel-wise diffusion tensor imaging (DTI) comparisons and probabilistic tractography in a large sample of phenotyped patients with IBS (n=33) and in HCs (n=93). Patients had lower fractional anisotropy (FA) in thalamic regions, the basal ganglia (BG) and sensory/motor association/integration regions as well as higher FA in frontal lobe regions and the corpus callosum. In addition, patients had reduced mean diffusivity (MD) within the globus pallidus (GP) and higher MD in the thalamus, internal capsule, and coronal radiata projecting to sensory/motor regions, suggestive of differential changes in axon/dendritic density in these regions. Sex differences in FA and MD were also observed in the patients but not in HCs. Probabilistic tractography in patients confirmed a higher degree of connectivity between the thalamus and prefrontal cortex, as well as between the medial dorsal thalamic nuclei and anterior cingulate cortex, and a lower degree of connectivity between the GP and thalamus. Together, these results support the hypothesis that patients with chronically recurring visceral pain from IBS have long-term microstructural changes within the brain, particularly in regions associated with integration of sensory information and corticothalamic modulation.

Diffusion tensor imaging and brain volumetry in Fabry disease patients

Fabry disease is a rare lysosomal storage disorder leading to cellular accumulation of globotriaosylceramide, especially in blood vessels. It is associated with severe early onset cerebrovascular disease and kidney and heart failure. The purpose of this study was to reveal possible disturbances in white matter integrity in Fabry disease patients using voxelwise diffusion-tensor imaging (DTI) analysis. Twelve Fabry disease patients, along with 13 healthy controls, underwent DTI and structural MRI. Voxel-based analysis of the DTI data was performed to assess possible differences in DTI parameters between Fabry disease patients and healthy controls. A selective region of interest analysis was performed for healthy volunteers and Fabry disease patients having a mild burden of T2-hyperintense lesions. We also measured normalised brain tissue volumes and performed a voxel-based volume analysis for grey matter. Voxel-based analysis of DTI data showed areas of significantly reduced fractional anisotropy and increased mean diffusivity in patients with Fabry disease. Eight patients had a mild burden of white matter lesions on their T2 scans. Region of interest analysis on areas showing reduced fractional anisotropy in voxelwise analysis also revealed reduced fractional anisotropy values in this patient group compared to eight healthy volunteers. The brain volume analyses did not reveal significant differences between the Fabry disease patients and the controls. These findings suggest a microstructural damage in brain white matter of Fabry disease patients, which can be revealed before excessive white matter lesions load is visible on conventional MR scans.

Extensive white matter abnormalities in patients with first-episode schizophrenia: A diffusion tensor imaging (DTI) study

BackgroundPrevious voxelwise Diffusion Tensor Imaging (DTI) investigations of white matter in first-episode schizophrenia (FESZ) have been limited to the analysis of Fractional Anisotropy (FA) and mean diffusivity (MD), with their findings inconsistent in terms of the anatomical locations and extent of abnormalities. This study examines white matter abnormalities in FESZ, compared with healthy controls, using a tract-based spatial statistics (TBSS) approach applied to multiple measures of tract integrity, and correlates these findings with symptom severity. MethodsSeventeen first-episode patients with schizophrenia and seventeen age- and gender-matched healthy controls (HC) participated in this imaging study where FA, MD, and axial and radial diffusivities were compared between the two groups using TBSS. ResultsFirst-episode patients with schizophrenia showed lower FA values in the genu and body of corpus callosum, the internal capsule, the external capsule, the fornix, the superior, inferior fronto-occipital fasciculus, the cingulum, and the uncinate fasciculus compared with HC. Increased MD and radial diffusivity were shown in virtually all white matter regions. There was no significant difference, however, observed for axial diffusivity between the two groups. Pearson correlation analysis showed that the FA values of the right inferior fronto-occipital fasciculus were positively correlated with positive symptoms, negative symptoms, and total correct items of the Wisconsin Card Sorting Test. FA values of right external capsule also showed significant positive correlation with category completed scores of the WCST. ConclusionsThese data suggest extensive, possibly myelin related white matter disruptions in FESZ.

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence. DTI was performed in 78 healthy subjects aged 8-21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence. In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age. These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.

Abnormal asymmetry of white matter integrity in schizophrenia revealed by voxelwise diffusion tensor imaging

A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right-handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract-based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 × (left - right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward-shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex.

A diffusion tensor brain template for Rhesus Macaques

Diffusion tensor imaging (DTI) is a powerful and noninvasive imaging method for characterizing tissue microstructure and white matter organization in the brain. While it has been applied extensively in research studies of the human brain, DTI studies of non-human primates have been performed only recently. The growing application of DTI in rhesus monkey studies would significantly benefit from a standardized framework to compare findings across different studies. A very common strategy for image analysis is to spatially normalize (co-register) the individual scans to a representative template space. This paper presents the development of a DTI brain template, UWRMAC-DTI271, for adolescent Rhesus Macaque (Macaca mulatta) monkeys. The template was generated from 271 rhesus monkeys, collected as part of a unique brain imaging genetics study. It is the largest number of animals ever used to generate a computational brain template, which enables the generation of a template that has high image quality and accounts for variability in the species. The quality of the template is further ensured with the use of DTI-TK, a well-tested and high-performance DTI spatial normalization method in human studies. We demonstrated its efficacy in monkey studies for the first time by comparing it to other commonly used scalar-methods for DTI normalization. It is anticipated that this template will play an important role in facilitating cross-site voxelwise DTI analyses in Rhesus Macaques. Such analyses are crucial in investigating the role of white matter structure in brain function, development, and other psychopathological disorders for which there are well-validated non-human primate models.

Relationships of brain white matter microstructure with clinical and MR measures in relapsing‐remitting multiple sclerosis

To assess the relationships of microstructural damage in the cerebral white matter (WM), as measured by diffusion tensor imaging (DTI), with clinical parameters and magnetic resonance imaging (MRI) measures of focal tissue damage in patients with multiple sclerosis (MS). Forty-five relapsing-remitting (RR) MS patients (12 male, 33 female; median age = 29 years, Expanded Disability Status Scale (EDSS) = 1.5, disease duration = 3 years) were studied. T2-lesion masks were created and voxelwise DTI analyses performed with Tract-Based Spatial Statistics (TBSS). T2-lesion volume (T2-LV) was significantly (P < 0.05, corrected) correlated with fractional anisotropy (FA) in both lesions and normal-appearing WM (NAWM). Relationships (P = 0.08, corrected) between increasing EDSS score and decreasing FA were found in the splenium of the corpus callosum (sCC) and along the pyramidal tract (PY). All FA associations were driven by changes in the perpendicular (to primary tract direction) diffusivity. No significant global and voxelwise FA changes were found over a 2-year follow-up. FA changes related to clinical disability in RR-MS patients with minor clinical disability are localized to specific WM tracts such as the sCC and PY and are driven by changes in perpendicular diffusivity both within lesions and NAWM. Longitudinal DTI measurements do not seem able to chart the early disease course in the WM of MS patients.