Regional White Matter Microstructure Research Articles

Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder.

To investigate whether response to lithium treatment in pediatric bipolar disorder can be predicted by changes in white matter microstructure in key cortico-limbic tracts involved in emotion regulation. Eighteen clinically referred lithium-naive patients (mean age 15.5years) were administered clinical rating scales and diffusion tensor imaging (DTI) examinations at baseline and following 4weeks of lithium treatment. Clinical ratings were repeated following 8 weeks of treatment. Patients with Clinical Global Impressions (CGI) ratings of 1 ("very much improved") or 2 ("much improved") were classified as responders. Ten healthy volunteers received baseline and follow-up DTI examinations. Using the ENIGMA pipeline, we investigated the relationship between changes in fractional anisotropy (FA) in the cingulum hippocampus (CGH) and clinical response to lithium. Patients demonstrated significantly lower FA compared to healthy volunteers in the left and right CGH white matter at baseline. Following 4weeks of lithium treatment, FA in the left CGH increased in patients, but no significant changes in FA were observed among the untreated healthy volunteers. Lithium responders had a significantly greater increase in FA compared to non-responders. Moreover, baseline (pre-treatment) FA in the left CGH white matter significantly predicted week 8 overall CGI severity score, with post hoc analyses indicating that these effects were evident for both severity of depression and mania. Our findings suggest that response to lithium treatment in pediatric bipolar disorder is associated with normalization of white matter microstructure in regions associated with emotion processing.

Predictors of Memory in Healthy Aging: Polyunsaturated Fatty Acid Balance and Fornix White Matter Integrity.

Recent evidence demonstrates that age and disease-related decline in cognition depends not only upon degeneration in brain structure and function, but also on dietary intake and nutritional status. Memory, a potential preclinical marker of Alzheimer’s disease, is supported by white matter integrity in the brain and dietary patterns high in omega-3 and omega-6 polyunsaturated fatty acids. However, the extent to which memory is supported by specific omega-3 and omega-6 polyunsaturated fatty acids, and the degree to which this relationship is reliant upon microstructure of particular white matter regions is not known. This study therefore examined the cross-sectional relationship between empirically-derived patterns of omega-3 and omega-6 polyunsaturated fatty acids (represented by nutrient biomarker patterns), memory, and regional white matter microstructure in healthy, older adults. We measured thirteen plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids, memory, and regional white matter microstructure in 94 cognitively intact older adults (65 to 75 years old). A three-step mediation analysis was implemented using multivariate linear regressions, adjusted for age, gender, education, income, depression status, and body mass index. The mediation analysis revealed that a mixture of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids is linked to memory and that white matter microstructure of the fornix fully mediates the relationship between this pattern of plasma phospholipid polyunsaturated fatty acids and memory. These results suggest that memory may be optimally supported by a balance of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acids through the preservation of fornix white matter microstructure in cognitively intact older adults. This report provides novel evidence for the benefits of plasma phospholipid omega-3 and omega-6 polyunsaturated fatty acid balance on memory and underlying white matter microstructure.

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function.

BackgroundDyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type.AimsThis study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions.Patients and methodsThirty-three participants with dyskinetic CP (mean ± SD age: 24.42 ± 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains.ResultsWhite matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum).ConclusionThe widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult.

Prediction of neurodevelopment using linear regression model and forward feature selection of near‐term regional white matter microstructure in children born preterm

Prediction of neurodevelopment using linear regression model and forward feature selection of near‐term regional white matter microstructure in children born preterm

Prediction of language development using forward feature selection and linear regression model of near‐term regional brain white matter microstructure in children born preterm

Prediction of language development using forward feature selection and linear regression model of near‐term regional brain white matter microstructure in children born preterm

Trait conscientiousness and the personality meta-trait stability are associated with regional white matter microstructure.

Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait ‘stability’, which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations.

White Matter Microstructural Integrity and Neurobehavioral Outcome of HIV-Exposed Uninfected Neonates.

The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth.Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated.Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants.This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes.

A study of the effects of prenatal alcohol exposure on white matter microstructural integrity at birth.

Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions in children. However, the temporal and regional specificity of such changes and their behavioural consequences are less known. Here we explore the integrity of regional white matter microstructure in infants with in utero exposure to alcohol, shortly after birth. Twenty-eight alcohol-exposed and 28 healthy unexposed infants were imaged using diffusion tensor imaging sequences to evaluate white matter integrity using validated tract-based spatial statistics analysis methods. Second, diffusion values were extracted for group comparisons by regions of interest. Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity were compared between groups and associations with measures from the Dubowitz neonatal neurobehavioural assessment were examined. Lower AD values (p<0.05) were observed in alcohol-exposed infants in the right superior longitudinal fasciculus compared with non-exposed infants. Altered FA and MD values in alcohol-exposed neonates in the right inferior cerebellar were associated with abnormal neonatal neurobehaviour. These exploratory data suggest that prenatal alcohol exposure is associated with reduced white matter microstructural integrity even early in the neonatal period. The association with clinical measures reinforces the likely clinical significance of this finding. The location of the findings is remarkably consistent with previously reported studies of white matter structural deficits in older children with a diagnosis of foetal alcohol spectrum disorders.

Widespread effects of alcohol on white matter microstructure.

Evidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter (WM) tracts, which can impact executive functions important to achieve and maintain abstinence. Global and regional WM microstructure was assessed using diffusion magnetic resonance measures of fractional anisotropy (FA) for 31 abstinent alcoholics (ALC) with an average of 25years of abuse and approximately 5years of sobriety and 20 nonalcoholic control (NC) participants. Data processing was conducted with FreeSurfer and FSL processing streams. Voxelwise processing of the FA data was carried out using tract-based spatial statistics. Clusters of significance were created to provide a quantitative summary of highly significant regions within the voxelwise analysis. Widespread, bilateral reductions in FA were observed in ALC as compared to NC participants in multiple frontal, temporal, parietal, and cerebellar WM tracts. FA in the left inferior frontal gyrus was associated with drinking severity. This study found widespread reductions in WM integrity in a group of ALC compared to NC participants, with most pronounced effects in frontal and superior tracts. Decreased FA throughout the frontostriatal circuits that mediate inhibitory control may result in impulsive behavior and inability to maintain sobriety.

White Matter Microstructure and Cognition in Adolescents with Congenital Heart Disease

To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA). We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r = 0.39; P = .006), inattention/hyperactivity symptoms correlated with right precentral FA (r = -0.39; P = .006) and left parietal FA (r = -0.30; P = .04), executive function correlated with right precentral FA (r = -0.30; P = .04), and visual-spatial skills correlated with right frontal FA (r = 0.30; P = .04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r = 0.29; P = .047). Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to that seen in healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy.

Regional white matter microstructure in very preterm infants: Predictors and 7 year outcomes

The aims of this study were to investigate regional white matter microstructural differences between very preterm (VPT) (<30 weeks' gestational age and/or <1250 g) and full term (FT) (≥37 weeks' gestational age) infants at term corrected age with diffusion tensor imaging, and to explore perinatal predictors of diffusion measures, and the relationship between regional diffusion measures and neurodevelopmental outcomes at age 7 years in VPT children. Mean (MD) (p = .003), axial (AD) (p = .008), and radial diffusivity (RD) (p = .003) in total white matter were increased in VPT compared with FT infants, with similar fractional anisotropy (FA) in the two groups. There was little evidence that group-wise differences were specific to any of the 8 regions studied for each hemisphere. Perinatal white matter abnormality and intraventricular hemorrhage (grade III or IV) were associated with increased diffusivity in the white matter of VPT infants. Higher white matter diffusivity measures of the inferior occipital and cerebellar region at term-equivalent age were associated with increased risk of impairments in motor and executive function at 7 years in VPT children, but there was little evidence for associations with IQ or memory impairment. In conclusion, myelination is likely disrupted or delayed in VPT infants, especially those with perinatal brain abnormality (BA). Altered diffusivity at term-equivalent age helps explain impaired functioning at 7 years. This study defines the nature of microstructural alterations in VPT infant white matter, assists in understanding the associated risk factors, and is the first study to reveal an important link between inferior occipital and cerebellar white matter disorganization in infancy, and executive and motor functioning 7 years later.

Body growth and brain development in premature babies: an MRI study

Prematurity and intrauterine growth restriction are associated with neurodevelopmental disabilities. To assess the relationship between growth status and regional brain volume (rBV) and white matter microstructure in premature babies at around term-equivalent age. Premature infants (n= 27) of gestational age (GA): 29.8 ± 2.1weeks, with normal brain MRI scans were studied at corrected age: 41.2 ± 1.4weeks. The infants were divided into three groups: 1) appropriate for GA at birth and at the time of MRI (AGA), 2) small for GA at birth with catch-up growth at the time of MRI (SGAa) and 3) small for GA at birth with failure of catch-up growth at the time of MRI (SGAb). The T1-weighted images were segmented into 90rBVs using the SPM8/IBASPM and differences among groups were assessed. Fractional anisotropy (FA) was measured bilaterally in 15 fiber tracts and its relationship to GA and somatometric measurements was explored. Lower rBV was observed in SGAb in superior and anterior brain areas. A positive correlation was demonstrated between FA and head circumference and body weight. Body weight was the only significant predictor for FA (P< 0.05). In premature babies, catch-up growth is associated with regional brain volume catch-up at around term-equivalent age, starting from the brain areas maturing first. Body weight seems to be a strong predictor associated with WM microstructure in brain areas related to attention, language, cognition, memory and executing functioning.

White matter microstructure correlates of inhibition and task-switching in adolescents

Although protracted prefrontal gray matter development is associated with concomitant executive function (EF) development in adolescents, few studies have explored the relationship between white matter and EF. This study examined the relationship between white matter microstructure and two aspects of EF, inhibition and task-switching, in a sample of 84 adolescents using diffusion tensor imaging (DTI). Tract-Based Spatial Statistics (TBSS) were used to examine fractional anisotropy (FA) and mean diffusivity (MD). Adolescents completed the Color-Word Interference task from the Delis–Kaplan Executive Function System, a clinical version of the Stroop task. Inhibition and task-switching performance were group normalized and measured using both reaction time and errors. Performance and the interaction of age and performance were regressed on FA and MD white matter skeletons, controlling for age and IQ, separately for inhibition and task-switching. Follow up analyses examined the relative contributions of axial and radial diffusivities. Greater FA in the anterior corona radiata (ACR) was associated with better inhibition, independent of age. Greater FA in the SCR and precentral gyrus white matter were associated with better task-switching, regardless of age, whereas an association between FA in the ACR and task-switching was dependent on age. There were no significant associations between MD and performance. Results suggest better inhibition and task-switching are associated with greater integrity of white matter microstructure in regions supporting cross-cortical and cortical–subcortical connections stemming from the prefrontal cortex. These findings are consistent with functional studies of cognitive control and models of EF that propose separate, yet related, latent factors.

Associations between T1 white matter lesion volume and regional white matter microstructure in aging

White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43-85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age-associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal-appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity.

Age-Related Changes in the Neurophysiology of Language in Adults: Relationship to Regional Cortical Thinning and White Matter Microstructure

Although reading skill remains relatively stable with advancing age in humans, neurophysiological measures suggest potential reductions in efficiency of lexical information processing. It is unclear whether these age-related changes are secondary to decreases in regional cortical thickness and/or microstructure of fiber tracts essential to language. Magnetoencephalography, volumetric MRI, and diffusion tensor imaging were performed in 10 young (18-33 years) and 10 middle-aged (42-64 years) human individuals to evaluate the spatiotemporal dynamics and structural correlates of age-related changes in lexical-semantic processing. Increasing age was associated with reduced activity in left temporal lobe regions from 250 to 350 ms and in left inferior prefrontal cortex from 350 to 450 ms (i.e., N400). Hierarchical regression indicated that age no longer predicted left inferior prefrontal activity after cortical thickness and fractional anisotropy (FA) of the uncinate fasciculus (UF) were considered. Interestingly, FA of the UF was a stronger predictor of the N400 response than cortical thickness. Age-related reductions in left-lateralization of language responses were observed between 250 and 350 ms, and were associated with left temporal thinning and frontotemporal FA reductions. N400 reductions were not associated with poorer task performance. Rather, increasing age was associated with reduction in the left prefrontal N400, which in turn was also associated with slower response time. These results reveal that changes in the neurophysiology of language occur by middle age and appear to be partially mediated by structural brain loss. These neurophysiological changes may reflect an adaptive process that ensues as communication between left perisylvian regions declines.

Poster #153 SOCIAL COGNITION IN EARLY-ONSET-SCHIZOPHRENIA, HIGH FUNCTIONING AUTISM AND ASPERGER SYNDROME

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adult participants (25 ASD and 66 neurotypicals; age: 18–60 years). We examined the relationship between regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging) and autistic traits (using Autism Spectrum Quotient). Our findings show grey matter differences in regions including the orbitofrontal cortex and lingual gyrus, and suggestive evidence for white matter microstructure differences in tracts including the superior longitudinal fasciculus being related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

Response inhibition is associated with white matter microstructure in children

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor cortex (preSMA), and subthalamic nucleus. Though the brain's fibre tracts are known to develop during childhood, little is known about how fibre tract development within this network relates to developing behavioural control. Here we examined the relationship between response inhibition, as measured with the stop-signal task, and indices of regional white matter microstructure in typically-developing children. We hypothesized that better response inhibition performance would be associated with higher fractional anisotropy (FA) in fibre tracts within right IFG and preSMA after controlling for age. Mean FA and diffusivity values were extracted from right and left IFG and preSMA. As hypothesized, faster response inhibition was significantly associated with higher FA and lower perpendicular diffusivity in both the right IFG and the right preSMA, possibly reflecting faster speed of neural conduction within more densely packed or better myelinated fibre tracts. Moreover, both of these effects remained significant after controlling for age and whole brain estimates of these DTI parameters. Interestingly, right IFG and preSMA FA contributed additively to the prediction of performance variability. Observed associations may be related to variation in phase of maturation, to activity-dependent alterations in the network subserving response inhibition, or to stable individual differences in underlying neural system connectivity.

Microstructural but Not Macrostructural Disruption of White Matter in Women with Chronic Alcoholism

The results of in vivo neuroimaging studies assessing whether and where brain white matter damage occurs in alcoholic women is controversial. To address this controversy, we examined regional white matter macrostructure and microstructure, the latter of which may be more sensitive to the detection of subtle fiber disruption than gross measures of size. Accordingly, we used conventional magnetic resonance imaging (MRI) to quantify regional callosal size and diffusion tensor imaging (DTI) to examine intravoxel coherence (fractional anisotropy, FA) and intervoxel coherence (C) of white matter of the genu and splenium of the corpus callosum and of the centrum semiovale in 12 detoxified alcoholic women and 18 control women. Additional analyses examined sex differences in FA and C in alcoholic women compared with alcoholic men. Despite absence of group differences in regional areas of callosal macrostructure, the alcoholic women had lower FA and C in genu and centrum semiovale than the control group of women. These measures also correlated with total lifetime consumption of alcohol and performance on a test of visual search in the alcoholic women. Sex comparisons revealed similar extents of FA abnormality in the genu and centrum semiovale in alcoholic men and women and differential effects in other DTI measures, with abnormalities present in splenium FA and C in the men and abnormalities present in centrum C in the women. These results provide in vivo evidence for disruption of white matter microstructure in alcoholic women not necessarily detectable with coarser measures of white matter mass and perhaps antedating its appearance.

Equivalent disruption of regional white matter microstructure in ageing healthy men and women.

Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.