White Matter Tract Microstructure Research Articles

Clinical Features Post Anterior Cruciate Ligament Reconstruction Associated with Structural Alterations in Corticospinal Tract.

Structural evidence for corticospinal tract (CST) abnormality between patients with ACLR and healthy controls, and the relationships between CST structure and clinical features of the patients (e.g., objective sensorimotor outcomes, postoperative duration) are lacking. To investigate whether the structural features of CST 1) differ between patients with ACLR and healthy controls, and 2) were associated with clinical features in patients following ACLR. Cross-sectional study. Sports medicine laboratory. Twenty-six patients who had undergone ACLR and twenty-six healthy controls were enrolled in this cross-sectional investigation. Using the CST as the region of interest, we performed diffusion tensor imaging to measure the microstructure of white matter tracts. Between-group comparisons and correlation analyses with clinical features in patients with ACLR were performed. The patients with ACLR showed significant, moderate lower fractional anisotropy (FA, Cohen's d = -0.666, 95% CIs -1.221 to -0.104), lower axial diffusivity (AD, Cohen's d = -0.526, 95% CIs -1.077 to 0.030), and higher radial diffusivity (RD, Cohen's d = 0.514, 95% CIs -0.042 to 1.064) when compared to that of healthy controls, with the RD values being significantly correlated with the postoperative duration (r = 0.623, p < 0.001) after controlling the age, sex, and BMI in patients with ACLR. This study revealed that patients with ACLR have impaired integrity (lower FA values and higher RD values) in the CST contralateral to the ACLR injured limb in comparison with healthy controls. Decreased integrity (higher RD) of the CST in patients was significantly associated with longer postoperative duration, which hinted that impaired structural integrity of the CST may be a maladaptive process of neuroplasticity in ACLR.

Correction to: White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Correction to: White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Altered fornix integrity is associated with sleep apnea-related hypoxemia in mild cognitive impairment.

The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55-86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea-hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water-corrected diffusion tensor imaging. Higher levels of OSA-related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. OSA may contribute to fornix damage and memory dysfunction in MCI. Sleep apnea-related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.

Impacts of dioxin exposure on brain connectivity estimated by DTI analysis of MRI images in men residing in contaminated areas of Vietnam.

Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam. In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates. The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels. It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders.

White matter tract microstructure, macrostructure, and associated cortical gray matter morphology across the lifespan

Abstract Characterizing how, when, and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white matter microstructure, white matter macrostructure, and morphology of the cortex associated with white matter pathways. We analyzed four large, high-quality, cross-sectional datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways—describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological differences at different stages of the lifespan. Third, we show unique trajectories of age associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that are expected to be useful for studying normal and abnormal white matter development and degeneration.

Early, low-dose hydrocortisone and near-term brain connectivity in extremely preterm infants.

Postnatal steroids are used to prevent bronchopulmonary dysplasia in extremely preterm infants but may have adverse effects on brain development. We assessed connectivity metrics of major cerebral and cerebellar white matter pathways at near-term gestational age among infants who did or did not receive a standardized regimen of hydrocortisone during the first 10 days of life. Retrospective cohort study. Infants born <28 weeks: Protocol group (n = 33) received at least 50% and not more than 150% of an intended standard dose of 0.5 mg/kg hydrocortisone twice daily for 7 days, then 0.5 mg/kg per day for 3 days; Non-Protocol group (n = 22), did not receive protocol hydrocortisone or completed <50% of the protocol dose. We assessed group differences in near-term diffusion MRI mean fractional anisotropy (FA) and mean diffusivity (MD) across the corticospinal tract, inferior longitudinal fasciculus, corpus callosum and superior cerebellar peduncle. Groups were comparable in gestational age, post-menstrual age at scan, medical complications, bronchopulmonary dysplasia, and necrotizing enterocolitis. No significant large effect group differences were identified in mean FA or MD in any cerebral or cerebellar tract. Low dose, early, postnatal hydrocortisone was not associated with significant differences in white matter tract microstructure at near-term gestational age. This study compared brain microstructural connectivity as a primary outcome among extremely preterm infants who did or did not receive early postnatal hydrocortisone. Low dose hydrocortisone in the first 10 days of life was not associated with significant differences in white matter microstructure in major cerebral and cerebellar pathways. Hydrocortisone did not have a significant effect on early brain white matter circuits.

Overweight/Obesity-related microstructural alterations of the fimbria-fornix in the ABCD study: The role of aerobic physical activity.

Childhood overweight/obesity has been associated with negative consequences related to brain function and may involve alterations in white matter pathways important for cognitive and emotional processing. Aerobic physical activity is a promising lifestyle factor that could restore white matter alterations. However, little is known about either regional white matter alterations in children with overweight/obesity or the effects of aerobic physical activity targeting the obesity-related brain alterations in children. Using a large-scale cross-sectional population-based dataset of US children aged 9 to 10 years (n = 8019), this study explored the associations between overweight/obesity and microstructure of limbic white matter tracts, and examined whether aerobic physical activity may reduce the overweight/obesity-related white matter alterations in children. The primary outcome measure was restriction spectrum imaging (RSI)-derived white matter microstructural integrity measures. The number of days in a week that children engaged in aerobic physical activity for at least 60 minutes per day was assessed. We found that females with overweight/obesity had lower measures of integrity of the fimbria-fornix, a major limbic-hippocampal white matter tract, than their lean peers, while this difference was not significant in males. We also found a positive relationship between the number of days of aerobic physical activity completed in a week and integrity measures of the fimbria-fornix in females with overweight/obesity. Our results provide cross-sectional evidence of sex-specific microstructural alteration in the fimbria-fornix in children with overweight/obesity and suggest that aerobic physical activity may play a role in reducing this alteration. Future work should examine the causal direction of the relationship between childhood overweight/obesity and brain alterations and evaluate potential interventions to validate the effects of aerobic physical activity on this relationship.

The Assessment of White Matter Integrity Alteration Pattern in Patients with Brain Tumor Utilizing Diffusion Tensor Imaging: A Systematic Review.

Alteration in the surrounding brain tissue may occur in the presence of a brain tumor. The present study aims to assess the characteristics and criteria of the pattern of white matter tract microstructure integrity alteration in brain tumor patients. The Scopus, PubMed/Medline, and Web of Science electronic databases were searched for related articles based on the guidelines established by PRISMA. Twenty-five studies were selected on the morphological changes of white matter tract integrity based on the differential classification of white matter tract (WMT) patterns in brain tumor patients through diffusion tensor imaging (DTI). The characterization was based on two criteria: the visualization of the tract-its orientation and position-and the DTI parameters, which were the fractional anisotropy and apparent diffusion coefficient. Individual evaluations revealed no absolute, mutually exclusive type of tumor in relation to morphological WMT microstructure integrity changes. In most cases, different types and grades of tumors have shown displacement or infiltration. Characterizing morphological changes in the integrity of the white matter tract microstructures is vital in the diagnostic and prognostic evaluation of the tumor's progression and could be a potential assessment for the early detection of possible neurological defects that may affect the patient, as well as aiding in surgery decision-making.

Characterizing White Matter Changes along Fibers in Treatment-Naive Pediatric Posttraumatic Stress Disorder

Children and adolescents are more susceptible than adults to developing posttraumatic stress disorder (PTSD). Pediatric PTSD is characterized by functional alterations in brain fear circuitry, but little is known about the underlying microstructural changes; previous work has mainly focused on the corpus callosum. This study is aimed at investigating brain-wide microstructural abnormalities in pediatric PTSD, their relationship to age and sex, and their potential diagnostic value. The microstructure of major white matter tracts was assessed from diffusion tensor images acquired from 24 treatment-naive non-comorbid PTSD patients &lt;18 years and 24 trauma-exposed non-PTSD controls (TENP) matched for age, sex, and years of education. Statistical analyses included pointwise comparisons, correlations with symptom severity, and diagnosis-by-age/sex interactions; support vector machine analyses were conducted to determine whether microstructure distinguishes PTSD from TENP. Compared with TENP, pediatric PTSD patients showed higher fractional anisotropy and lower radial diffusivity in right superior longitudinal fasciculus and lower axial diffusivity in right uncinate fasciculus. These white matter microstructural abnormalities were highly correlated with PTSD symptom severity. No significant diagnosis by age or sex interaction was observed. The pointwise axial diffusivity measurements presented the best PTSD vs. TENP classification performance. In summary, pediatric PTSD patients showed clinically relevant microstructural abnormalities in uncinate and superior longitudinal fasciculus, which extend understanding of pediatric PTSD neurobiology beyond the corpus callosum and have diagnostic potential in distinguishing stressed individuals with and without PTSD.

Anxiety symptoms and puberty interactively predict lower cingulum microstructure in preadolescent Latina girls

Preadolescence is a period of increased vulnerability for anxiety, especially among Latina girls. Reduced microstructure (fractional anisotropy; FA) of white matter tracts between limbic and prefrontal regions may underlie regulatory impairments in anxiety. However, developmental research on the association between anxiety and white matter microstructure is mixed, possibly due to interactive influences with puberty. In a sample of 39 Latina girls (8–13 years), we tested whether pubertal stage moderated the association between parent- and child-reported anxiety symptoms and FA in the cingulum and uncinate fasciculus. Parent- but not child-reported anxiety symptoms predicted lower cingulum FA, and this effect was moderated by pubertal stage, such that this association was only significant for prepubertal girls. Neither anxiety nor pubertal stage predicted uncinate fasciculus FA. These findings suggest that anxiety is associated with disruptions in girls’ cingulum white matter microstructure and that this relationship undergoes maturational changes during puberty.

White matter microstructure predicts individual differences in infant fear (But not anger and sadness).

We examine neural correlates of discrete expressions of negative emotionality in infants to determine whether the microstructure of white matter tracts at 1 month of age foreshadows the expression of specific negative emotions later in infancy. Infants (n=103) underwent neuroimaging at 1-month, and mothers reported on infant fear, sadness, and anger at 6, 12, and 18 months using the Infant Behavior Questionnaire-Revised. Levels and developmental change in fear, sadness, and anger were estimated from mother reports. Relations between MRI and infant emotion indicated that 1-month white matter microstructure was differentially associated with level and change in infant fear, but not anger or sadness, in the left stria terminalis (p<0.05, corrected), a tract that connects frontal and tempo-parietal regions and has been implicated in emerging psychopathology in adults. More relaxed constraints on significance (p<0.10, corrected) revealed that fear was associated with lower white matter microstructure bilaterally in the inferior portion of the stria terminalis and regions within the sagittal stratum. Results suggest the neurobehavioral uniqueness of fear as early as 1 month of age in regions that are associated with potential longer-term outcomes. This work highlights the early neural precursors of fearfulness, adding to literature explaining the psychobiological accounts of affective development. HIGHLIGHTS: Expressions of infant fear and anger, but not sadness, increase from 6 to 18 months of age. Early neural architecture in the stria terminalis is related to higher initial levels and increasing fear in infancy. After accounting for fear, anger and sadness do not appear to be associated with differences in early white matter microstructure. This work identifies early neural precursors of fearfulness as early as 1-month of age.

Impact of early brain lesions on the optic radiations in children with cerebral palsy.

Due to their early brain lesion, children with unilateral spastic cerebral palsy (USCP) present important changes in brain gray and white matter, often manifested by perturbed sensorimotor functions. We predicted that type and side of the lesion could influence the microstructure of white matter tracts. Using diffusion tensor imaging in 40 children with USCP, we investigated optic radiation (OR) characteristics: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). First, we compared the OR of the lesional and non-lesional hemisphere. Then we evaluated the impact of the brain lesion type (periventricular or cortico-subcortical) and side in the differences observed in the lesional and non-lesional OR. Additionally, we examined the relationship between OR characteristics and performance of a visuospatial attention task. We observed alterations in the OR of children with USCP on the lesional hemisphere compared with the non-lesional hemisphere in the FA, MD and RD. These differences were influenced by the type of lesion and by the side of the lesion. A correlation was also observed between FA, MD and RD and the visuospatial assessment mainly in children with periventricular and right lesions. Our results indicate an important role of the timing and side of the lesion in the resulting features of these children’s OR and probably in the compensation resulting from neuroplastic changes.

Transcutaneous auricular vagus nerve stimulation (taVNS) given for poor feeding in at-risk infants also improves their motor abilities.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that may improve oromotor skills when paired with feeding in at-risk infants, but effects on other motor function and how motor function relates to white matter (WM) microstructure are unknown. In this prospective study, infants failing oral feeds and slated for gastrostomy tube (G-tube) placement received taVNS paired with bottle feeding daily for 2-3 weeks. The effects of taVNS-paired feeding on general and specific head movements were investigated using the Specific Test of Early infant motor Performance (STEP) and diffusion MRI obtained before and after taVNS treatment. Scores between and within groups (taVNS responders, attained full oral feeds; non-responders, received G-tubes) were compared. Performance on head movement items improved significantly in responders but not in non-responders (p < 0.05). Total STEP scores were significantly higher in responders after taVNS treatment than non-responders (p = 0.04). One STEP item, rolling by arm, was associated with significantly greater change in WM tract microstructure (p < 0.05) in the responders. These results suggest that pairing feeding with taVNS may affect specific head and neck movements to a greater extent in infants who are able to attain full oral feeds.

White matter microstructural correlates of associative learning in the oldest-old.

The ability to learn associations between events is critical for everyday functioning (e.g., decision making, social interactions) and has been attributed to structural differences in white matter tracts connecting cortical regions to the hippocampus (e.g., fornix) and striatum (e.g., internal capsule) in younger-old adults (ages 65-85 years). However, evidence of associative learning has not been assessed within oldest-old adults (ages 90+ years), despite its relevance to other extensively characterized cognitive abilities in the oldest-old and the relatively large effect of advanced age on the microstructural composition of these white matter tracts. We acquired multicompartment diffusion-weighted magnetic resonance imaging data from 22 oldest-old adults without dementia (mean age = 92.91 ± 1.44 years) who also completed an associative learning task. Behavioral results revealed significantly better associative learning performance during later task stages, as expected if participants incidentally learned the cue-cue-target associations for frequently occurring event triplets. Moreover, better learning performance was significantly predicted by better microstructure of cortico-striatal white matter (posterior limb of the internal capsule). Finding that associative learning abilities in the 10th decade of life are supported by better microstructure of white matter tracts connecting the cortex to the striatum underscores their importance to learning performance across the entire lifespan.

Investigating longitudinal changes to frontal cortico-striatal tracts in Huntington’s disease: the IMAGE-HD study

The striatum is the principal site of disease pathology in Huntington’s disease and contains neural connections to numerous cortical brain regions. Studies examining abnormalities to neural connections find that white matter integrity is compromised in HD; however, further regional, and longitudinal investigation is required. This paper is the first longitudinal investigation into region-based white-matter integrity changes in Huntington’s Disease. The aim of this study was to better understand how disease progression impacts white matter tracts connecting the striatum to the prefrontal and motor cortical regions in HD. We used existing neuroimaging data from IMAGE-HD, comprised of 25 pre-symptomatic, 27 symptomatic, and 25 healthy controls at three separate time points (baseline, 18-months, 30-months). Fractional anisotropy, axial diffusivity and radial diffusivity were derived as measures of white matter microstructure. The anatomical regions of interest were identified using the Desikan-Killiany brain atlas. A Group by Time repeated measures ANCOVA was conducted for each tract of interest and for each measure. We found significantly lower fractional anisotropy and significantly higher radial diffusivity in the symptomatic group, compared to both the pre-symptomatic group and controls (the latter two groups did not differ from each other), in the rostral middle frontal and superior frontal tracts; as well as significantly higher axial diffusivity in the rostral middle tracts only. We did not find a Group by Time interaction for any of the white matter integrity measures. These findings demonstrate that whilst the microstructure of white matter tracts, extending from the striatum to these regions of interest, are compromised during the symptomatic stages of Huntington’s disease, 36-month follow-up did not show progressive changes in these measures. Additionally, no correlations were found between clinical measures and tractography changes, indicating further investigations into the relationship between tractography changes and clinical symptoms in Huntington’s disease are required.

Impaired corticospinal tract in chronic ankle instability: A diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) study at 7.0 Tesla

ObjectivesElectrophysiological studies have revealed that abnormal function of the corticospinal pathway might contribute to chronic ankle instability, but structural evidence underlying the abnormality is lacking. The purpose of this study was to quantitate microstructural differences between corticospinal tracts in patients with chronic ankle instability and healthy controls. DesignCross-sectional. MethodsSeventeen patients with chronic ankle instability and sixteen healthy controls underwent diffusion weighted-imaging scans using an ultra-high-field 7.0 Tesla magnetic resonance imaging scanner. We focused on corticospinal tracts as a region of interest and performed classical diffusion tensor imaging and the advanced neurite orientation dispersion and density imaging outcomes that measured the microstructure of white matter tracts. Correlation analyses were also performed between the significantly different diffusion outcomes in both groups. ResultsThe patients with chronic ankle instability showed significantly lower fractional anisotropy (p-corrected = 0.045) and higher orientation dispersion index (p-corrected = 0.033) when compared with healthy controls. These two measures were significantly correlated in the healthy controls (r = −0.56, p = 0.024) and the CAI patient group (r = −0.53, p = 0.029). ConclusionsThis study revealed that the contralateral corticospinal tract of the unstable ankle in patients with chronic ankle instability exhibited impaired integrity, which was associated with abnormally organized neurites. We propose that this is a useful target for the clinical assessment of chronic ankle instability and the development of targeted neuromuscular rehabilitation.

Modeling the Properties of White Matter Tracts Using Diffusion Tensor Imaging to Characterize Patterns of Injury in Aging and Neurodegenerative Disease.

Diffusion tensor imaging (DTI) is a relatively novel magnetic resonance-based imaging methodology that can provide valuable insight into the microstructure of white matter tracts of the brain. In this paper, we evaluated the reliability and reproducibility of deriving a semi-automated pseudo-atlas DTI tractography method vs. standard atlas-based analysis alternatives, for use in clinical cohorts with neurodegeneration and ventriculomegaly. We showed that the semi-automated pseudo-atlas DTI tractography method was reliable and reproducible across different cohorts, generating 97.7% of all tracts. However, DTI metrics obtained from both methods were significantly different across the majority of cohorts and white matter tracts (p < 0.001). Despite this, we showed that both methods produced patterns of white matter injury that are consistent with findings reported in the literature and with DTI profiles generated from these methodologies. Scatter plots comparing DTI metrics obtained from each methodology showed that the pseudo-atlas method produced metrics that implied a more preserved neural structure compared to its counterpart. When comparing DTI metrics against a measure of ventriculomegaly (i.e., Evans’ Index), we showed that the standard atlas-based method was able to detect decreasing white matter integrity with increasing ventriculomegaly, while in contrast, metrics obtained using the pseudo-atlas method were sensitive for stretch or compression in the posterior limb of the internal capsule. Additionally, both methods were able to show an increase in white matter disruption with increasing ventriculomegaly, with the pseudo-atlas method showing less variability and more specificity to changes in white matter tracts near to the ventricles. In this study, we found that there was no true gold-standard for DTI methodologies or atlases. Whilst there was no congruence between absolute values from DTI metrics, differing DTI methodologies were still valid but must be appreciated to be variably sensitive to different changes within white matter injury occurring concurrently. By combining both atlas and pseudo-atlas based methodologies with DTI profiles, it was possible to navigate past such challenges to describe white matter injury changes in the context of confounders, such as neurodegenerative disease and ventricular enlargement, with transparency and consistency.

DNA methylation in relation to gestational age and brain dysmaturation in preterm infants.

Preterm birth is associated with dysconnectivity of structural brain networks and is a leading cause of neurocognitive impairment in childhood. Variation in DNA methylation is associated with early exposure to extrauterine life but there has been little research exploring its relationship with brain development. Using genome-wide DNA methylation data from the saliva of 258 neonates, we investigated the impact of gestational age on the methylome and performed functional analysis to identify enriched gene sets from probes that contributed to differentially methylated probes or regions. We tested the hypothesis that variation in DNA methylation could underpin the association between low gestational age at birth and atypical brain development by linking differentially methylated probes with measures of white matter connectivity derived from diffusion MRI metrics: peak width skeletonized mean diffusivity, peak width skeletonized fractional anisotropy and peak width skeletonized neurite density index. Gestational age at birth was associated with widespread differential methylation at term equivalent age, with genome-wide significant associations observed for 8870 CpG probes (P < 3.6 × 10−8) and 1767 differentially methylated regions. Functional analysis identified 14 enriched gene ontology terms pertaining to cell–cell contacts and cell–extracellular matrix contacts. Principal component analysis of probes with genome-wide significance revealed a first principal component that explained 23.5% of the variance in DNA methylation, and this was negatively associated with gestational age at birth. The first principal component was associated with peak width of skeletonized mean diffusivity (β = 0.349, P = 8.37 × 10−10) and peak width skeletonized neurite density index (β = 0.364, P = 4.15 × 10−5), but not with peak width skeletonized fraction anisotropy (β = −0.035, P = 0.510); these relationships mirrored the imaging metrics’ associations with gestational age at birth. Low gestational age at birth has a profound and widely distributed effect on the neonatal saliva methylome that is apparent at term equivalent age. Enriched gene ontology terms related to cell–cell contacts reveal pathways that could mediate the effect of early life environmental exposures on development. Finally, associations between differential DNA methylation and image markers of white matter tract microstructure suggest that variation in DNA methylation may provide a link between preterm birth and the dysconnectivity of developing brain networks that characterizes atypical brain development in preterm infants.

Exploring the course of adolescent anxiety and depression: associations with white matter tract microstructure.

Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12-18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months' time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents.

Pediatric PTSD is characterized by age- and sex-related abnormalities in structural connectivity.

Pediatric post-traumatic stress disorder (pPTSD) is a prevalent and pervasive form of mental illness comprising a disparate constellation of psychiatric symptoms. Emerging evidence suggests that pPTSD may be characterized by alterations in functional networks traversing the brain. Yet, little is known about pathological changes in the structural tracts underlying functional connectivity. In adults, PTSD is linked to widespread change in white matter integrity throughout the brain, yet similar studies with youth populations have yet to be conducted. Current understanding of the nature and treatment of pPTSD may be enhanced by examining alterations in white matter, while further untangling effects of age and sex. Here, we assess the microstructure of 12 major white matter tracts in a sample of well-phenotyped youth with PTSD. Measures of fractional anisotropy were derived from diffusion tensor images acquired from 82 unmediated youth (ages 8-18), of whom 39 met criteria for pPTSD. Diagnosis of pPTSD was linked to remarkable age- and sex-linked differences in the microstructure of major white matter tracts including the uncinate fasciculus, cingulum bundle, and inferior longitudinal fasciculus. In each case, youth with PTSD show an absence of increased white matter integrity with age, suggesting an altered pattern of neurodevelopment that may contribute to persistence or worsening of illness. Broadly, our results suggest abnormal white matter development in pediatric PTSD, a finding which may contribute to illness persistence, comorbidity with other disorders, and poorer prognosis across time. Critically, these findings further speak to the nature of pPTSD as a 'whole-brain' disorder.