Measures Of White Matter Microstructure Research Articles

Reduced tract length of the medial forebrain bundle and the anterior thalamic radiation in bipolar disorder with melancholic depression

BackgroundThe supero-lateral medial forebrain bundle (slMFB) and the anterior thalamic radiation (ATR) play a core role in reward anticipation and motivational processes. In this study, the slMFB and the ATR were investigated in a group of depressed bipolar disorder (BD) and in healthy controls (HC) using tract length as a measure of fibre geometry and fractional anisotropy (FA) as a measure of white matter microstructure. We hypothesized reduced tract length and FA of the slMFB and the ATR in BD. We expect alterations to be driven by the melancholic subtype. MethodsNineteen depressed patients with BD and 19 HC matched for age and gender underwent diffusion-weighted magnetic resonance imaging (MRI) scans. Diffusion tensor imaging (DTI) based tractography was used to reconstruct bilateral slMFB and ATR. Mean tract length and FA were computed for the slMFB and the ATR. Mixed-model ANCOVAs and post-hoc ANCOVAs, controlling for age and intracranial volume, were used to compare tract length and FA of bilateral slMFB and ATR between HC and BD and between HC and subgroups with melancholic and non-melancholic symptoms. ResultsIn BD we found a significantly shortened tract length of the right slMFB and ATR in BD compared to HC. Subgroup analyses showed that these findings were driven by the melancholic subgroup. Mean-FA did not differ between HC and BD. LimitationsSample size ConclusionsTract length of the right slMFB and the right ATR is reduced in BD. Those changes of fibre geometry are driven by the melancholic subtype.

Baseline White Matter Is Associated With Physical Fitness Change in Preclinical Alzheimer's Disease.

White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer’s disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with “normal-appearing” WM microstructure. Data acquired on magnetic resonance imaging was used to measure “normal-appearing” WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer’s disease with distinctive patterns for each PF test.

Multimodality neuroimaging brain-age in UK biobank: relationship to biomedical, lifestyle, and cognitive factors

The brain-age paradigm is proving increasingly useful for exploring aging-related disease and can predict important future health outcomes. Most brain-age research uses structural neuroimaging to index brain volume. However, aging affects multiple aspects of brain structure and function, which can be examined using multimodality neuroimaging. Using UK Biobank, brain-age was modeled in n = 2205 healthy people with T1-weighted MRI, T2-FLAIR, T2∗, diffusion-MRI, task fMRI, and resting-state fMRI. In a held-out healthy validation set (n = 520), chronological age was accurately predicted (r = 0.78, mean absolute error = 3.55 years) using LASSO regression, higher than using any modality separately. Thirty-four neuroimaging phenotypes were deemed informative by the regression (after bootstrapping); predominantly gray-matter volume and white-matter microstructure measures. When applied to new individuals from UK Biobank (n = 14,701), significant associations with multimodality brain-predicted age difference (brain-PAD) were found for stroke history, diabetes diagnosis, smoking, alcohol intake and some, but not all, cognitive measures (corrected p < 0.05). Multimodality neuroimaging can improve brain-age prediction, and derived brain-PAD values are sensitive to biomedical and lifestyle factors that negatively impact brain and cognitive health.

Differences in White Matter Microstructure Among Children With Developmental Coordination Disorder

Developmental coordination disorder (DCD) is a motor impairment that significantly interferes with activities of daily living. Little is known about the cause of DCD and how it develops, making it difficult to understand why children with DCD struggle in learning motor skills and to determine the best intervention to optimize function. To characterize white matter differences using diffusion tensor imaging in children with and without DCD. This cross-sectional study collected diffusion tensor imaging data at BC Children's Hospital Research Institute in Vancouver, British Columbia, Canada, from September 2014 to January 2017. Using a sample of convenience, children with DCD and children without DCD aged 8 to 12 years underwent magnetic resonance imaging. Data analysis was conducted from January 2017 to January 2020. The main outcome measures were diffusion parameters, including fractional anisotropy and mean, axial, and radial diffusivity, which are thought to provide an indirect measure of white matter microstructure. Tract-based spatial statistics, a voxelwise statistical analysis of diffusion parameters, were conducted using a 2-group comparison design matrix with age and attention as covariates. Thirty children without DCD (mean [SD] age, 9.9 [1.4] years; 21 [70%] boys) and 31 children with DCD (mean [SD] age, 10.1 [1.2] years; 26 [84%] boys) were included in the study. Compared with children without DCD, children with DCD were characterized by significantly lower fractional anisotropy and axial diffusivity in regions of white matter pathways associated with motor and sensorimotor processing, including the corticospinal tract (fractional anisotropy: mean [SD], 0.54 [0.03] vs 0.51 [0.03]; P < .001; axial diffusivity: mean [SD], 0.13 [0.98] vs 0.12 [0.46]; P = .01), posterior thalamic radiation at the retrolenticular part of the internal capsule (axial diffusivity: mean [SD], 0.14 [0.57] vs 0.14 [0.44]; P = .01), and cerebellar pathways (eg, superior cerebellar peduncle, fractional anisotropy: mean [SD], 0.49 [0.05] vs 0.46 [0.03]; P = .03; axial diffusivity: mean [SD], 0.14 [0.66] vs 0.14 [0.63]; P = .009). There were no significant differences in mean diffusivity and radial diffusivity between children with and without DCD. These findings suggest that children with DCD show significant brain differences in motor and sensorimotor white matter pathways compared with children without DCD. The pattern of diffusion parameters in children with DCD suggests that axonal development may be disrupted in this neurodevelopmental disorder.

Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA...

History of childhood maltreatment is associated with reduced fractional anisotropy of the accumbofrontal 'reward' tract in healthy adults.

The deleterious outcomes associated with exposure to childhood maltreatment (CM) are well known and may be at least partially mediated by self-harm behaviors. It has been suggested that these self-harm behaviors serve as a means of decreasing negative mood states but the effects of CM on health outcomes may be much more sinister. A wealth of data suggest that CM may lead to experience-dependent changes in neural circuits underlying reward processes; processes associated with many harmful behaviors. The present study examined the relationship between a history of CM and the microstructure of a white matter tract that may be central to reward processes. Healthy adults (N = 122) were assessed with a diffusion tensor imaging (DTI) exam and the Childhood Trauma Questionnaire (CTQ). Probabilistic tractography was used to delineate the accumbofrontal "reward" tract, connecting the orbitofrontal cortex and nucleus accumbens, and measures of white matter microstructure were extracted. We then examined whether variation in CTQ scores were associated with variation in the microstructure of this tract as measured by fractional anisotropy (FA). After accounting for the effects of age and sex, the CTQ total score accounted for approximately 6% of the variance of FA in the accumbofrontal tract (F(3, 121) = 5.74; p = .001). Post hoc analyses indicated that the overall severity of CM, rather than a specific type of maltreatment, drove this result. These findings indicate that CM influences white matter microstructure in a fiber tract that is likely central to reward processes and adds to a growing literature implicating CM in long-term health-related outcomes.

Neurometabolites and sport-related concussion: From acute injury to one year after medical clearance.

Sport-related concussion is associated with acute disturbances in neurometabolic function, with effects that may last weeks to months after injury. However, is presently unknown whether these disturbances resolve at medical clearance to return to play (RTP) or continue to evolve over longer time intervals. Moreover, little is known about how these neurometabolic changes correlate with other measures of brain physiology. In this study, these gaps were addressed by evaluating ninety-nine (99) university-level athletes, including 33 with sport-related concussion and 66 without recent injury, using multi-parameter magnetic resonance imaging (MRI), which included single-voxel spectroscopy (SVS), diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). The concussed athletes were scanned at the acute phase of injury (27/33 imaged), medical clearance to RTP (25/33 imaged), one month post-RTP (25/33 imaged) and one year post-RTP (13/33 imaged). We measured longitudinal changes in N-acetyl aspartate (NAA) and myo-inositol (Ins), over the course of concussion recovery. Concussed athletes showed no significant abnormalities or longitudinal change in NAA values, whereas Ins was significantly elevated at RTP and one month later. Interestingly, Ins response was attenuated by a prior history of concussion. Subsequent analyses identified significant associations between Ins values, DTI measures of white matter microstructure and fMRI measures of functional connectivity. These associations varied over the course of concussion recovery, suggesting that elevated Ins values at RTP and beyond reflect distinct changes in brain physiology, compared to acute injury. These findings provide novel information about neurometabolic recovery after a sport-related concussion, with evidence of disturbances that persist beyond medical clearance to RTP.

The white matter connectome as an individualized biomarker of language impairment in temporal lobe epilepsy.

The distributed white matter network underlying language leads to difficulties in extracting clinically meaningful summaries of neural alterations leading to language impairment. Here we determine the predictive ability of the structural connectome (SC), compared with global measures of white matter tract microstructure and clinical data, to discriminate language impaired patients with temporal lobe epilepsy (TLE) from TLE patients without language impairment. T1- and diffusion-MRI, clinical variables (CVs), and neuropsychological measures of naming and verbal fluency were available for 82 TLE patients. Prediction of language impairment was performed using a robust tree-based classifier (XGBoost) for three models: (1) a CV-model which included demographic and epilepsy-related clinical features, (2) an atlas-based tract-model, including four frontotemporal white matter association tracts implicated in language (i.e., the bilateral arcuate fasciculus, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus), and (3) a SC-model based on diffusion MRI. For the association tracts, mean fractional anisotropy was calculated as a measure of white matter microstructure for each tract using a diffusion tensor atlas (i.e., AtlasTrack). The SC-model used measurement of cortical-cortical connections arising from a temporal lobe subnetwork derived using probabilistic tractography. Dimensionality reduction of the SC was performed with principal components analysis (PCA). Each model was trained on 49 patients from one epilepsy center and tested on 33 patients from a different center (i.e., an independent dataset). Randomization was performed to test the stability of the results. The SC-model yielded a greater area under the curve (AUC; .73) and accuracy (79%) compared to both the tract-model (AUC: .54, p<.001; accuracy: 70%, p<.001) and the CV-model (AUC: .59, p<.001; accuracy: 64%, p<.001). Within the SC-model, lateral temporal connections had the highest importance to model performance, including connections similar to language association tracts such as links between the superior temporal gyrus to pars opercularis. However, in addition to these connections many additional connections that were widely distributed, bilateral and interhemispheric in nature were identified as contributing to SC-model performance. The SC revealed a white matter network contributing to language impairment that was widely distributed, bilateral, and lateral temporal in nature. The distributed network underlying language may be why the SC-model has an advantage in identifying sub-components of the complex fiber networks most relevant for aspects of language performance.

A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children

BackgroundThe core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30–40 months) suggest individuals with ASD have increased measures of WM FA earlier in development.MethodsWe analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1–49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion.ResultsCompared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males.ConclusionsThe current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD.

Lagged Coupled Changes Between White Matter Microstructure and Processing Speed in Healthy Aging: A Longitudinal Investigation

Age-related differences in white matter (WM) microstructure have been linked to lower performance in tasks of processing speed in healthy older individuals. However, only few studies have examined this link in a longitudinal setting. These investigations have been limited to the correlation of simultaneous changes in WM microstructure and processing speed. Still little is known about the nature of age-related changes in WM microstructure, i.e., regionally distinct vs. global changes. In the present study, we addressed these open questions by exploring whether previous changes in WM microstructure were related to subsequent changes in processing speed: (a) 1 year later; or (b) 2 years later. Furthermore, we investigated whether age-related changes in WM microstructure were regionally specific or global. We used data from four occasions (covering 4 years) of the Longitudinal Healthy Aging Brain (LHAB) database project (N = 232; age range at baseline = 64–86). As a measure of WM microstructure, we used mean fractional anisotropy (FA) in 10 major WM tracts averaged across hemispheres. Processing speed was measured with four cognitive tasks. Statistical analyses were conducted with bivariate latent change score (LCS) models. We found, for the first time, evidence for lagged couplings between preceding changes in FA and subsequent changes in processing speed 2 years, but not 1 year later in some of the WM tracts (anterior thalamic radiation, superior longitudinal fasciculus). Our results supported the notion that FA changes were different between regional WM tracts rather than globally shared, with some tracts showing mean declines in FA, and others remaining relatively stable across 4 years.

Associations of physical activity and screen time with white matter microstructure in children from the general population

Physical activity and sedentary behaviors have been linked to a variety of general health benefits and problems. However, few studies have examined how physical activity during childhood is related to brain development, with the majority of work to date focusing on cardio-metabolic health. This study examines the association between physical activity and screen time with white matter microstructure in the general pediatric population. In a sample of 2532 children (10.12 ± 0.58 years; 50.04% boys) from the Generation R Study, a population-based cohort in Rotterdam, the Netherlands, we assessed physical activity and screen time using parent-reported questionnaires. Magnetic resonance imaging of white matter microstructure was conducted using diffusion tensor imaging. Total physical activity was positively associated with global fractional anisotropy (β = 0.057, 95% CI = 0.016, 0.098, p = 0.007) and negatively associated with global mean diffusivity (β = −0.079, 95% CI = −0.120, −0.038, p < 0.001), two commonly derived scalar measures of white matter microstructure. Two components of total physical activity, outdoor play and sport participation, were positively associated with global fractional anisotropy (β = 0.041, 95% CI=(0.000, 0.083), p = 0.047; β = 0.053, 95% CI=(0.010, 0.096), p = 0.015, respectively) and inversely associated with global mean diffusivity (β = −0.074, 95% CI= (−0.114, −0.033), p < 0.001; β = −0.043, 95% CI=(-0.086, 0.000), p = 0.049, respectively). No associations were observed between screen time and white matter microstructure (p > 0.05). This study provides new evidence that physical activity is modestly associated with white matter microstructure in children. In contrast, complementing other recent evidence on cognition, screen time was not associated with white matter microstructure. Causal inferences from these modest associations must be interpreted cautiously in the absence of longitudinal data. However, these data still offer a promising avenue for future work to explore to what extent physical activity may promote healthy white matter development.

Altered Resting State Functional Activity and Microstructure of the White Matter in Migraine With Aura.

Introduction: Brain structure and function were reported to be altered in migraine. Importantly our earlier results showed that white matter diffusion abnormalities and resting state functional activity were affected differently in the two subtypes of the disease, migraine with and without aura. Resting fluctuation of the BOLD signal in the white matter was reported recently. The question arising whether the white matter activity, that is strongly coupled with gray matter activity is also perturbed differentially in the two subtypes of the disease and if so, is it related to the microstructural alterations of the white matter.Methods: Resting state fMRI, 60 directional DTI images and high-resolution T1 images were obtained from 51 migraine patients and 32 healthy volunteers. The images were pre-processed and the white matter was extracted. Independent component analysis was performed to obtain white matter functional networks. The differential expression of the white matter functional networks in the two subtypes of the disease was investigated with dual-regression approach. The Fourier spectrum of the resting fMRI fluctuations were compared between groups. Voxel-wise correlation was calculated between the resting state functional activity fluctuations and white matter microstructural measures.Results: Three white matter networks were identified that were expressed differently in migraine with and without aura. Migraineurs with aura showed increased functional connectivity and amplitude of BOLD fluctuation. Fractional anisotropy and radial diffusivity showed strong correlation with the expression of the frontal white matter network in patients with aura.Discussion: Our study is the first to describe changes in white matter resting state functional activity in migraine with aura, showing correlation with the underlying microstructure. Functional and structural differences between disease subtypes suggest at least partially different pathomechanism, which may necessitate handling of these subtypes as separate entities in further studies.

GENETIC ARCHITECTURE OF PSYCHIATRIC AND ADDICTION TRAITS IN THE MILLION VETERAN PROGRAM

Autism spectrum disorder (ASD) is a complex and genetically heterogeneous neuropsychiatric disease affecting as many as 1 in 68 children. Large scale genetic sequencing of individuals along the autism spectrum has uncovered several genetic risk factors for ASD; however, understanding how, and to what extent, individual genes contribute to the overall disease phenotype remains unclear. Neuroimaging studies of ASD have revealed a wide spectrum of structural and functional perturbations that are thought to reflect, in part, the complex genetic heterogeneity underpinning ASD. These perturbations, in both preclinical models and clinical patients, were identified in preclinical genetic models and ASD patients when compared to control populations; however, few studies have directly explored intrinsic differences between the models themselves. To better understand the degree and extent to which individual genes associated with ASD differ in their contribution to global measures of white matter microstructure, diffusion tensor imaging (DTI) was acquired from three novel rat genetic models of ASD (Fmr1, Nrxn1, and Pten) and DTI parameters of fractional anisotropy, mean, axial, and radial diffusivity were measured. Subsequent whole-brain voxel-wise analysis comparing each genetic model to each other (Fmr1:Nrxn1; Fmr1:Pten; Nrxn1:Pten) identified no significant differences in any comparison for all diffusion parameters assessed (FA, AD, MD, RD).

A NOVEL APPROACH TO IDENTIFYING MODIFIABLE PROTECTIVE FACTORS FOR DEPRESSION IN THE CONTEXT OF GENETIC AND ENVIRONMENTAL RISK

Autism spectrum disorder (ASD) is a complex and genetically heterogeneous neuropsychiatric disease affecting as many as 1 in 68 children. Large scale genetic sequencing of individuals along the autism spectrum has uncovered several genetic risk factors for ASD; however, understanding how, and to what extent, individual genes contribute to the overall disease phenotype remains unclear. Neuroimaging studies of ASD have revealed a wide spectrum of structural and functional perturbations that are thought to reflect, in part, the complex genetic heterogeneity underpinning ASD. These perturbations, in both preclinical models and clinical patients, were identified in preclinical genetic models and ASD patients when compared to control populations; however, few studies have directly explored intrinsic differences between the models themselves. To better understand the degree and extent to which individual genes associated with ASD differ in their contribution to global measures of white matter microstructure, diffusion tensor imaging (DTI) was acquired from three novel rat genetic models of ASD (Fmr1, Nrxn1, and Pten) and DTI parameters of fractional anisotropy, mean, axial, and radial diffusivity were measured. Subsequent whole-brain voxel-wise analysis comparing each genetic model to each other (Fmr1:Nrxn1; Fmr1:Pten; Nrxn1:Pten) identified no significant differences in any comparison for all diffusion parameters assessed (FA, AD, MD, RD).

Converging evidence points towards a role of insulin signaling in regulating compulsive behavior

Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior.

Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults.

The metabolic serum marker HbA1c has been associated with both impaired cognitive performance and altered white matter integrity in patients suffering from diabetes mellitus. However, it remains unclear if higher levels of HbA1c might also affect brain structure and function in healthy subjects. With the present study we therefore aimed to investigate the relationship between HbA1c levels and cognitive performance as well as white matter microstructure in healthy, young adults. To address this question, associations between HbA1c and cognitive measures (NIH Cognition Toolbox) as well as DTI-derived imaging measures of white matter microstructure were investigated in a publicly available sample of healthy, young adults as part of the Humane Connectome Project (n = 1206, mean age = 28.8 years, 45.5% male). We found that HbA1c levels (range 4.1-6.3%) were significantly inversely correlated with measures of cognitive performance. Higher HbA1c levels were associated with significant and widespread reductions in fractional anisotropy (FA) controlling for age, sex, body mass index, ethnicity, and education. FA reductions were furthermore found to covary with measures of cognitive performance. The same pattern of results could be observed in analyses restricted to participants with HBA1c levels below 5.7%. The present study demonstrates that low-grade HbA1c variation below diagnostic threshold for diabetes is related to both cognitive performance and white matter integrity in healthy, young adults. These findings highlight the detrimental impact of metabolic risk factors on brain physiology and underscore the importance of intensified preventive measures independent of the currently applied diagnostic HbA1c cutoff scores.

Maternal Prenatal Stress Is Associated With Altered Uncinate Fasciculus Microstructure in Premature Neonates

BackgroundMaternal prenatal stress exposure (PNSE) increases risk for adverse psychiatric and behavioral outcomes in offspring. The biological basis for this elevated risk is poorly understood but may involve alterations to the neurodevelopmental trajectory of white matter tracts within the limbic system, particularly the uncinate fasciculus. Additionally, preterm birth is associated with both impaired white matter development and adverse developmental outcomes. In this study we hypothesized that higher maternal PNSE was associated with altered uncinate fasciculus microstructure in offspring. MethodsIn this study, 251 preterm infants (132 male, 119 female) (median gestational age = 30.29 weeks [range, 23.57–32.86 weeks]) underwent brain magnetic resonance imaging including diffusion-weighted imaging around term-equivalent age (median = 42.43 weeks [range, 37.86–45.71 weeks]). Measures of white matter microstructure were calculated for the uncinate fasciculus and the inferior longitudinal fasciculus, a control tract that we hypothesized was not associated with maternal PNSE. Multiple regressions were used to investigate the relationship among maternal trait anxiety scores, stressful life events, and white matter microstructure indices in the neonatal brain. ResultsAdjusting for gestational age at birth, postmenstrual age at scan, maternal age, socioeconomic status, sex, and number of days on parenteral nutrition, higher stressful life events scores were associated with higher axial diffusivity (β = .177, q = .007), radial diffusivity (β = .133, q = .026), and mean diffusivity (β = .149, q = .012) in the left uncinate fasciculus, and higher axial diffusivity (β = .142, q = .026) in the right uncinate fasciculus. ConclusionsThese findings suggest that PNSE is associated with altered development of specific frontolimbic pathways in preterm neonates as early as term-equivalent age.

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study

22q11.2 deletion syndrome (22q11DS)—a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22—is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6–52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen’s d’s ranging from −0.9 to −1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Molecular Senescence Is Associated With White Matter Microstructural Damage in Late-Life Depression

ObjectivesThe authors aim to investigate the association between white matter integrity and accelerated brain aging in late-life depression. MethodsThe authors measured senescence-associated secretory phenotype (SASP) index proteins, cognitive performance, and MRI diffusion tensor imaging (DTI) measures of fractional anisotropy and mean diffusivity-based indices of white matter microstructure measures in 56 older adults with remitted late-life depression. ResultsHigher SASP index was significantly correlated with older age (r = 0.42, p = 0.001) and worse executive function performance (r = −0.27, p = 0.04). After controlling for the effect of age, overall cognitive performance, and white matter hyperintensities, the association between SASP and left and right cingulate bundle mean diffusivity remained statistically significant. ConclusionsOur data suggest that, in the context of late-life depression, SASP proteins are associated with microstructural abnormalities in white matter tracts in brain and worse executive function performance.

Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment.

BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.