Microstructural abnormalities in children with post-traumatic stress disorder: a diffusion tensor imaging study at 3.0T.
ABSTRACT: Posttraumatic stress disorder (PTSD) is a severe anxiety disorder characterized by re-experiencing, avoidance and hyperarousal. Brain microstructure abnormalities in PTSD, especially in children, are not yet well characterized. The aim of this study was to use MR diffusion tensor imaging (DTI) to identify brain microstructure alterations in children with PTSD compared to non-PTSD controls who experienced the same time-limited trauma. We studied 27 children with PTSD and 24 age- and gender-matched traumatized controls without PTSD, who all experienced the 2008 Sichuan major earthquake. DTI data were acquired and analyzed in terms of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Children with PTSD showed an abnormal pattern, not only of FA, but also of the diffusivity measures MD, AD and RD. Most of the abnormal brain regions belonged to two important networks: the default-mode network, including precuneus and angular gyrus, and the salience network, including insula, putamen and thalamus. This DTI study identifies microstructural abnormalities of children with PTSD after a major earthquake, our results are consistent with the suggestion that pediatric PTSD is accompanied by a connectivity disequilibrium between the salience and default-mode networks, a finding of potential pathophysiological significance.
Project description:Studies of posttraumatic stress disorder (PTSD) are complicated by wide variability in the intensity and duration of prior stressors in patient participants, secondary effects of chronic psychiatric illness, and a variable history of treatment with psychiatric medications. In magnetic resonance imaging (MRI) studies, patient samples have often been small, and they were not often compared to similarly stressed patients without PTSD in order to control for general stress effects. Findings from these studies have been inconsistent. The present study investigated whole-brain microstructural alterations of white matter in a large drug-naive population who survived a specific, severe traumatic event (a major 8.0-magnitude earthquake). Using diffusion tensor imaging (DTI), we explored group differences between 88 PTSD patients and 91 matched traumatized non-PTSD controls in fractional anisotropy (FA), as well as its component elements axial diffusivity (AD) and radial diffusivity (RD), and examined these findings in relation to findings from deterministic DTI tractography. Relations between white matter alterations and psychiatric symptom severity were examined. PTSD patients, relative to similarly stressed controls, showed an FA increase as well as AD and RD changes in the white matter beneath left dorsolateral prefrontal cortex and forceps major. The observation of increased FA in the PTSD group suggests that the pathophysiology of PTSD after a specific acute traumatic event is distinct from what has been reported in patients with several years duration of illness. Alterations in dorsolateral prefrontal cortex may be an important aspect of illness pathophysiology, possibly via the region's established role in fear extinction circuitry. Use-dependent myelination or other secondary compensatory changes in response to heightened demands for threat appraisal and emotion regulation may be involved.
Project description:White matter (WM) microstructure, as determined by diffusion tensor imaging (DTI), is increasingly recognized as an important determinant of cognitive function and is also altered in neuropsychiatric disorders. Little is known about genetic and environmental influences on WM microstructure, especially in early childhood, an important period for cognitive development and risk for psychiatric disorders. We studied the heritability of DTI parameters, fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) along 34 tracts, including 10 bilateral fiber pathways and the respective subdivision, using quantitative tractography in a longitudinal sample of healthy children at 1?year (N?=?215) and 2?years (N?=?165) of age. We found that heritabilities for whole brain AD, RD, and FA were 0.48, 0.69, and 0.72 at age 1, and 0.59, 0.77, and 0.76 at age 2 and that mean heritabilities of tract-averaged AD, RD, and FA for individual bundles were moderate (over 0.4). However, the heritability of DTI change between 1 and 2?years of age was not significant for most tracts. We also demonstrated that point-wise heritability tended to be significant in the central portions of the tracts and was generally spatially consistent at ages 1 and 2?years. These results, especially when compared to heritability patterns in neonates, indicate that the heritability of WM microstructure is dynamic in early childhood and likely reflect heterogeneous maturation of WM tracts and differential genetic and environmental influences on maturation patterns.
Project description:The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. Analyses were undertaken in 284 healthy older twins (66% female; 79 MZ and 63 DZ pairs) from the Older Australian Twins Study. The average age of the sample was 69.82 (SD?=?4.76) years. Brain imaging scans were collected and DTI measures were estimated for the whole CC as well as its five subregions. Parcellation of the CC was performed using Analyze. In addition, white matter lesion (WMLs) burden was estimated. Heritability and genetic correlation analyses were undertaken using the SOLAR software package. Age, sex, scanner, handedness and blood pressure were considered as covariates. Heritability (h(2)) analysis for the DTI metrics of whole CC, indicated significant h(2) for fractional anisotropy (FA) (h(2)?=?0.56; p?=?2.89×10(-10)), mean diffusivity (MD) (h(2)?=?0.52; p?=?0.30×10(-6)), radial diffusivity (RD) (h(2)?=?0.49; p?=?0.2×10(-6)) and axial diffusivity (AD) (h(2)?=?0.37; p?=?8.15×10(-5)). We also performed bivariate genetic correlation analyses between (i) whole CC DTI measures and (ii) whole CC DTI measures with total brain WML burden. Across the DTI measures for the whole CC, MD and RD shared 84% of the common genetic variance, followed by MD-AD (77%), FA-RD (52%), RD-AD (37%) and FA-MD (11%). For total WMLs, significant genetic correlations indicated that there was 19% shared common genetic variance with whole CC MD, followed by CC RD (17%), CC AD (16%) and CC FA (5%). Our findings suggest that the CC microstructure is under moderate genetic control. There was also evidence of shared genetic factors between the CC DTI measures. In contrast, there was less shared genetic variance between WMLs and the CC DTI metrics, suggesting fewer common genetic variants.
Project description:Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder with a clinical presentation characterized by memory impairment and executive dysfunction. Our group previously demonstrated significant alterations in white matter microstructural metrics in AD compared to healthy older adults. We aimed to further investigate the relationship between white matter microstructure in AD and cognitive function, including memory and executive function.Methods: Diffusion tensor imaging (DTI) and neuropsychological data were downloaded from the AD Neuroimaging Initiative database for 49 individuals with AD and 48 matched healthy older adults. The relationship between whole-brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and composite scores of memory and executive function was examined. We also considered voxel-wise relationships using Tract-Based Spatial Statistics.Results: As expected, individuals with AD had lower composite scores on tests of memory and executive function, as well as disrupted white matter integrity (low FA, high MD, AxD, and RD) relative to healthy older adults in widespread regions, including the hippocampus. When the AD and healthy older adult groups were combined, we found significant relationships between DTI metrics (FA/MD/AxD/RD) and memory scores across widespread regions of the brain, including the medial temporal regions. We also found significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in widespread regions, including the frontal areas in the combined group. However, when the groups were examined separately, no significant relationships were found between DTI metrics (FA/MD/AxD/RD) and memory performance for either group. Further, we did not find any significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in the AD group, but we did observe significant relationships between FA/RD, and executive function in healthy older adults.Conclusion: White matter integrity is disrupted in AD. In a mixed sample of AD and healthy elderly persons, associations between measures of white matter microstructure and memory and executive cognitive test performance were evident. However, no significant linear relationship between the degree of white matter disruption and level of cognitive functioning (memory and executive abilities) was found in those with AD. Future longitudinal studies of the relations between DTI metrics and cognitive function in AD are required to determine whether DTI has potential to measure progression of AD and/or treatment efficacy.
Project description:Concussion pathophysiology in humans remains incompletely understood. Diffusion tensor imaging (DTI) has identified microstructural abnormalities in otherwise normal appearing brain tissue, using measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). The results of prior DTI studies suggest that acute alterations in microstructure persist beyond medical clearance to return to play (RTP), but these measures lack specificity. To better understand the observed effects, this study combined DTI with neurite orientation dispersion and density imaging (NODDI), which employs a more sophisticated description of water diffusion in the brain. A total of 66 athletes were recruited, including 33 concussed athletes, scanned within 7?days after concussion and at RTP, along with 33 matched controls. Both univariate and multivariate methods identified DTI and NODDI parameters showing effects of concussion on white matter. Spatially extensive decreases in FA and increases in AD and RD were associated with reduced intra-neurite water volume, at both the symptomatic phase of injury and RTP, indicating that effects persist beyond medical clearance. Subsequent analyses also demonstrated that concussed athletes with higher symptom burden and a longer recovery time had greater reductions in FA and increased AD, RD, along with increased neurite dispersion. This study provides the first longitudinal evaluation of concussion from acute injury to RTP using combined DTI and NODDI, significantly enhancing our understanding of the effects of concussion on white matter microstructure.
Project description:Previous voxel-based and regions-of-interest (ROI)-based diffusion tensor imaging (DTI) studies have found above-normal mean diffusivity (MD) and below-normal fractional anisotropy (FA) in subjects with attention-deficit/hyperactivity disorder (ADHD). However, findings remain mixed, and few studies have examined the contribution of ADHD familial liability to white matter microstructure.We used refined DTI tractography methods to examine MD, FA, axial diffusivity (AD), and radial diffusivity (RD) of the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major, forceps minor, superior longitudinal fasciculus, and uncinate fasciculus in children and adolescents with ADHD (n = 56), unaffected siblings of ADHD probands (n = 31), and healthy controls (n = 17).Subjects with ADHD showed significantly higher MD than controls in the anterior thalamic radiation, forceps minor, and superior longitudinal fasciculus. Unaffected siblings of subjects with ADHD displayed similar differences in MD as subjects with ADHD. Although none of the tested tracts showed a significant effect of FA, the tracts with elevated MD likewise displayed elevated AD both in subjects with ADHD and in unaffected siblings. Differences in RD between subjects with ADHD, unaffected siblings, and controls were not as widespread as differences in MD and AD.Our findings suggest that disruptions in white matter microstructure occur in several large white matter pathways in association with ADHD and indicate a familial liability for the disorder. Furthermore, MD may reflect these abnormalities more sensitively than FA.
Project description:<h4>Introduction</h4>The underlying microstructural properties of white matter differences in children born very preterm (<32?weeks gestational age) can be investigated in depth using multi-shell diffusion imaging. The present study compared white matter across the whole brain using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics in children born very preterm and full-term children at six years of age. We also investigated associations between white matter microstructure with early brain injury and developmental outcomes.<h4>Method</h4>Multi-shell diffusion imaging, T1-weighted anatomical MR images and developmental assessments were acquired in 23 children born very preterm (16 males; mean scan age: 6.57?±?0.34?years) and 24 full-term controls (10 males, mean scan age: 6.62?±?0.37?years). DTI metrics were obtained and neurite orientation dispersion index (ODI) and density index (NDI) were estimated using the NODDI diffusion model. FSL's tract-based spatial statistics were performed on traditional DTI metrics and NODDI metrics. Voxel-wise comparisons were performed to test between-group differences and within-group associations with developmental outcomes (intelligence and visual motor abilities) as well as early white matter injury and germinal matrix/intraventricular haemorrhage (GMH/IVH).<h4>Results</h4>In comparison to term-born children, the children born very preterm exhibited lower fractional anisotropy (FA) across many white matter regions as well as higher mean diffusivity (MD), radial diffusivity (RD), and ODI. Within-group analyses of the children born very preterm revealed associations between higher FA and NDI with higher IQ and VMI. Lower ODI was found within the corona radiata in those with a history of white matter injury. Within the full-term group, associations were found between higher NDI and ODI with lower IQ.<h4>Conclusion</h4>Children born very preterm exhibit lower FA and higher ODI than full-term children. NODDI metrics provide more biologically specific information beyond DTI metrics as well as additional information of the impact of prematurity and white matter microstructure on cognitive outcomes at six years of age.
Project description:It has been shown that cognitive training (CogTr) is effective and recuperative for older adults, and can be used to fight against cognitive decline. In this study, we investigated whether behavioural gains from CogTr would extend to white matter (WM) microstructure, and whether training-induced changes in WM integrity would be associated with improvements in cognitive function, using diffusion tensor imaging (DTI). 48 healthy community elderly were either assigned to multi-domain or single-domain CogTr groups to receive 24 sessions over 12 weeks, or to a control group. DTI was performed at both baseline and 12-month follow-up. Positive effects of multi-domain CogTr on long-term changes in DTI indices were found in posterior parietal WM. Participants in the multi-domain group showed a trend of long-term decrease in axial diffusivity (AD) without significant change in fractional anisotropy (FA), mean diffusivity (MD) or radial diffusivity (RD), while those in the control group displayed a significant FA decrease, and an increase in MD and RD. In addition, significant relationships between an improvement in processing speed and changes in RD, MD and AD were found in the multi-domain group. These findings support the hypothesis that plasticity of WM can be modified by CogTr, even in late adulthood.
Project description:<b>Background: </b>Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia.<br><br><b>Objectives: </b>To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60-77 years) from the general population.<br><br><b>Methods: </b>This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n?=?34) or control group (general health advice, n?=?26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed.<br><br><b>Results: </b>FA decreased, and cognition improved more in the intervention group compared to the control group (p?<?0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group.<br><br><b>Conclusion: </b>The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations.
Project description:Individual differences in white matter tract microstructure, measured with diffusion tensor imaging (DTI), demonstrate substantial heritability. However, it is unclear to what extent this heritability reflects global genetic influences or tract-specific genetic influences. The goal of the current study was to quantify the proportion of genetic and environmental variance in white matter tracts attributable to global versus tract-specific influences. We assessed fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) across 11 tracts and 22 subdivisions of these tracts in 392 middle-aged male twins from the Vietnam Era Twin Study of Aging (VETSA). In principal component analyses of the 11 white matter tracts, the first component, which represents the global signal, explained 50.1% and 62.5% of the variance in FA and MD, respectively. Similarly, the first principal component of the 22 tract subdivisions explained 38.4% and 47.0% of the variance in FA and MD, respectively. Twin modeling revealed that DTI measures of all tracts and subdivisions were heritable, and that genetic influences on global FA and MD accounted for approximately half of the heritability in the tracts or tract subdivisions. Similar results were observed for the AD and RD diffusion metrics. These findings underscore the importance of controlling for DTI global signals when measuring associations between specific tracts and outcomes such as cognitive ability, neurological and psychiatric disorders, and brain aging.