Spatiotemporal patterns of cortical microstructural maturation in children and adolescents with diffusion MRI.

Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. This study characterized cortical microstructural maturation using diffusion MRI (fwe-diffusion tensor imaging [DTI] and neurite orientation dispersion and density imaging [NODDI] multicompartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased, and fwe-DTI metrics decreased with age. By applying nonlinear growth models in a vertex-wise analysis, we observed a general posterior-to-anterior pattern of maturation, where the fwe-DTI measures mean diffusivity and radial diffusivity reached peak maturation earlier than the NODDI metrics neurite density index. Using non-negative matrix factorization, we found occipito-parietal cortical regions that correspond to lower order sensory domains mature earlier than fronto-temporal higher order association domains. Our findings corroborate previous histological and neuroimaging studies that show spatially varying patterns of cortical maturation that may reflect unique developmental processes of cytoarchitectonically determined regional patterns of change.

Mapping frontoinsular cortex from diffusion microstructure.

We developed a novel method for mapping the location, surface area, thickness, and volume of frontoinsular cortex (FI) using structural and diffusion magnetic resonance imaging. FI lies in the ventral part of anterior insular cortex and is characterized by its distinctive population von Economo neurons (VENs). Functional neuroimaging studies have revealed its involvement in affective processing, and histopathology has implicated VEN loss in behavioral-variant frontotemporal dementia and chronic alcoholism; however, structural neuroimaging of FI has been relatively limited. We delineated FI by jointly modeling cortical surface geometry and its coincident diffusion microstructure parameters. We found that neurite orientation dispersion in cortical gray matter can be used to map FI in specific individuals, and the derived measures reflect a range of behavioral factors in young adults from the Human Connectome Project (N=1052). FI volume was larger in the left hemisphere than the right (31%), and the percentage volume of FI was larger in women than men (15.3%). FI volume was associated with measures of decision-making (delay discounting, substance abuse), emotion (negative intrusive thinking and perception of hostility), and social behavior (theory of mind and working memory for faces). The common denominator is that larger FI size is related to greater self-control and social awareness.

More extensive white matter disruptions present in untreated obstructive sleep apnea than we thought: A large sample diffusion imaging study.

Obstructive sleep apnea (OSA) may lead to white mater (WM) disruptions and cognitive deficits. However, no studies have investigated the full extent of the brain WM, and its associations with cognitive deficits in OSA remain unclear. We thus applied diffusion tensor imaging (DTI) tractography with multi-fiber models and used atlas-based bundle-specific approach to investigate the WM abnormalities for various tracts of the cerebral cortex, thalamus, brainstem, and cerebellum in patients with untreated OSA. We enrolled 100 OSA patients and 63 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values mapped on 33 regions of interest including WM tracts of cortex, thalamus, brainstem, and cerebellum were obtained from tractography-based reconstructions. We compared FA/MD values between groups and correlated FA/MD with clinical data in the OSA group after controlling for age and body mass index. OSA patients showed significantly lower FA values in multiple WM fibers including corpus callosum, inferior fronto-occipital fasciculus, middle/superior longitudinal fasciculi, thalamic radiations, and uncinate (FDR <0.05). Higher FA values were found in medial lemniscus of patients compared to controls (FDR <0.05). Lower FA values of rostrum of corpus callosum correlated with lower visual memory performance in OSA group (p < .005). Our quantitative DTI analysis demonstrated that untreated OSA could negatively impact the integrity of pathways more broadly, including brainstem structures such as medial lemniscus, in comparison to previous findings. Fiber tract abnormalities of the rostral corpus callosum were associated with impaired visual memory in untreated OSA may provide insights into the related pathomechanism.

Aberrant functional connectivity between reward and inhibitory control networks in pre-adolescent binge eating disorder.

BACKGROUND: Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied. METHODS: 58 pre-adolescent children (aged 9-10-years) with BED (mBMI = 25.05; s.d. = 5.40) and 66 age, BMI and developmentally matched control children (mBMI = 25.78; s.d. = 0.33) were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward [orbitofrontal cortex (OFC), nucleus accumbens, amygdala] and inhibitory control [dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)] networks via hypothesis-driven seed-to-seed analyses, and secondary seed-to-voxel analyses. RESULTS: Findings revealed reduced FC between the dlPFC and amygdala, and between the ACC and OFC in pre-adolescent children with BED, relative to controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses. CONCLUSIONS: Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.

White matter microstructure in habit and reward circuits in anorexia nervosa: Insights from a neurite orientation dispersion and density imaging study.

BACKGROUND: Behavioral features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN. METHODS: In this brain imaging study, 29 female adolescents with partially or fully weight-restored AN and 27 healthy controls, all between 10 and 19 years, underwent whole-brain multi-shell diffusion tensor imaging. Utilizing neurite orientation dispersion and density imaging methods, we investigated group differences in white matter neurite density, orientation dispersion, and myelin density in tracts between prominent nodes of the reward circuit (ventral tegmental area (VTA) to nucleus accumbens (NAcc)) and the habit circuit (sensory motor area [SMA] to putamen). RESULTS: Findings revealed reduced neurite (F = 5.20, p = 0.027) and myelin density (F = 5.39, p = 0.025) in the left VTA-NAcc tract, and reduced orientation dispersion in the left (F = 7.00, p = 0.011) and right (F = 6.77, p = 0.012) VTA-NAcc tract. There were no significant group differences in the SMA-putamen tract. Significant relationships, after corrections, were not evident between tract microstructure and reward responsiveness, compulsive behaviors, illness duration, or BMI. CONCLUSIONS: Adolescents with AN exhibit less dense, undermyelinated, and less dispersed white matter tracts connecting prominent reward system nodes, which could potentially signify underutilization of this part of the reward circuit. These results provide a detailed examination of white matter microstructure in tracts underlying instrumental behavioral phenotypes contributing to illness in AN.

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues-such as incomplete mechanistic knowledge and faulty clinical trial design-a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

Microstructural properties within the amygdala and affiliated white matter tracts across adolescence.

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8-22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

THC Exposure is Reflected in the Microstructure of the Cerebral Cortex and Amygdala of Young Adults.

The endocannabinoid system serves a critical role in homeostatic regulation through its influence on processes underlying appetite, pain, reward, and stress, and cannabis has long been used for the related modulatory effects it provides through tetrahydrocannabinol (THC). We investigated how THC exposure relates to tissue microstructure of the cerebral cortex and subcortical nuclei using computational modeling of diffusion magnetic resonance imaging data in a large cohort of young adults from the Human Connectome Project. We report strong associations between biospecimen-defined THC exposure and microstructure parameters in discrete gray matter brain areas, including frontoinsular cortex, ventromedial prefrontal cortex, and the lateral amygdala subfields, with independent effects in behavioral measures of memory performance, negative intrusive thinking, and paternal substance abuse. These results shed new light on the relationship between THC exposure and microstructure variation in brain areas related to salience processing, emotion regulation, and decision making. The absence of effects in some other cannabinoid-receptor-rich brain areas prompts the consideration of cellular and molecular mechanisms that we discuss. Further studies are needed to characterize the nature of these effects across the lifespan and to investigate the mechanistic neurobiological factors connecting THC exposure and microstructural parameters.

Magnitude and timing of major white matter tract maturation from infancy through adolescence with NODDI.

White matter maturation is a nonlinear and heterogeneous phenomenon characterized by axonal packing, increased axon caliber, and a prolonged period of myelination. While current in vivo diffusion MRI (dMRI) methods, like diffusion tensor imaging (DTI), have successfully characterized the gross structure of major white matter tracts, these measures lack the specificity required to unravel the distinct processes that contribute to microstructural development. Neurite orientation dispersion and density imaging (NODDI) is a dMRI approach that probes tissue compartments and provides biologically meaningful measures that quantify neurite density index (NDI) and orientation dispersion index (ODI). The purpose of this study was to characterize the magnitude and timing of major white matter tract maturation with NODDI from infancy through adolescence in a cross-sectional cohort of 104 subjects (0.6-18.8 years). To probe the regional nature of white matter development, we use an along-tract approach that partitions tracts to enable more fine-grained analysis. Major white matter tracts showed exponential age-related changes in NDI with distinct maturational patterns. Overall, analyses revealed callosal fibers developed before association fibers. Our along-tract analyses elucidate spatially varying patterns of maturation with NDI that are distinct from those obtained with DTI. ODI was not significantly associated with age in the majority of tracts. Our results support the conclusion that white matter tract maturation is heterochronous process and, furthermore, we demonstrate regional variability in the developmental timing within major white matter tracts. Together, these results help to disentangle the distinct processes that contribute to and more specifically define the time course of white matter maturation.

Tractography reproducibility challenge with empirical data (TraCED): The 2017 ISMRM diffusion study group challenge.

BACKGROUND: Fiber tracking with diffusion-weighted MRI has become an essential tool for estimating in vivo brain white matter architecture. Fiber tracking results are sensitive to the choice of processing method and tracking criteria. PURPOSE: To assess the variability for an algorithm in group studies reproducibility is of critical context. However, reproducibility does not assess the validity of the brain connections. Phantom studies provide concrete quantitative comparisons of methods relative to absolute ground truths, yet do no capture variabilities because of in vivo physiological factors. The ISMRM 2017 TraCED challenge was created to fulfill the gap. STUDY TYPE: A systematic review of algorithms and tract reproducibility studies. SUBJECTS: Single healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T, two different scanners by the same manufacturer. The multishell acquisition included b-values of 1000, 2000, and 3000 s/mm2 with 20, 45, and 64 diffusion gradient directions per shell, respectively. ASSESSMENT: Nine international groups submitted 46 tractography algorithm entries each consisting 16 tracts per scan. The algorithms were assessed using intraclass correlation (ICC) and the Dice similarity measure. STATISTICAL TESTS: Containment analysis was performed to assess if the submitted algorithms had containment within tracts of larger volume submissions. This also serves the purpose to detect if spurious submissions had been made. RESULTS: The top five submissions had high ICC and Dice >0.88. Reproducibility was high within the top five submissions when assessed across sessions or across scanners: 0.87-0.97. Containment analysis shows that the top five submissions are contained within larger volume submissions. From the total of 16 tracts as an outcome relatively the number of tracts with high, moderate, and low reproducibility were 8, 4, and 4. DATA CONCLUSION: The different methods clearly result in fundamentally different tract structures at the more conservative specificity choices. Data and challenge infrastructure remain available for continued analysis and provide a platform for comparison. LEVEL OF EVIDENCE: 5 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:234-249.

Perivascular space fluid contributes to diffusion tensor imaging changes in white matter.

Diffusion tensor imaging (DTI) has been extensively used to map changes in brain tissue related to neurological disorders. Among the most widespread DTI findings are increased mean diffusivity and decreased fractional anisotropy of white matter tissue in neurodegenerative diseases. Here we utilize multi-shell diffusion imaging to separate diffusion signal of the brain parenchyma from non-parenchymal fluid within the white matter. We show that unincorporated anisotropic water in perivascular space (PVS) significantly, and systematically, biases DTI measures, casting new light on the biological validity of many previously reported findings. Despite the challenge this poses for interpreting these past findings, our results suggest that multi-shell diffusion MRI provides a new opportunity for incorporating the PVS contribution, ultimately strengthening the clinical and scientific value of diffusion MRI.

Neuroanatomical morphometric characterization of sex differences in youth using statistical learning.

Exploring neuroanatomical sex differences using a multivariate statistical learning approach can yield insights that cannot be derived with univariate analysis. While gross differences in total brain volume are well-established, uncovering the more subtle, regional sex-related differences in neuroanatomy requires a multivariate approach that can accurately model spatial complexity as well as the interactions between neuroanatomical features. Here, we developed a multivariate statistical learning model using a support vector machine (SVM) classifier to predict sex from MRI-derived regional neuroanatomical features from a single-site study of 967 healthy youth from the Philadelphia Neurodevelopmental Cohort (PNC). Then, we validated the multivariate model on an independent dataset of 682 healthy youth from the multi-site Pediatric Imaging, Neurocognition and Genetics (PING) cohort study. The trained model exhibited an 83% cross-validated prediction accuracy, and correctly predicted the sex of 77% of the subjects from the independent multi-site dataset. Results showed that cortical thickness of the middle occipital lobes and the angular gyri are major predictors of sex. Results also demonstrated the inferential benefits of going beyond classical regression approaches to capture the interactions among brain features in order to better characterize sex differences in male and female youths. We also identified specific cortical morphological measures and parcellation techniques, such as cortical thickness as derived from the Destrieux atlas, that are better able to discriminate between males and females in comparison to other brain atlases (Desikan-Killiany, Brodmann and subcortical atlases).

A Comparative evaluation of voxel-based spatial mapping in diffusion tensor imaging.

This paper presents a comparative evaluation of methods for automated voxel-based spatial mapping in diffusion tensor imaging studies. Such methods are an essential step in computational pipelines and provide anatomically comparable measurements across a population in atlas-based studies. To better understand their strengths and weaknesses, we tested a total of eight methods for voxel-based spatial mapping in two types of diffusion tensor templates. The methods were evaluated with respect to scan-rescan reliability and an application to normal aging. The methods included voxel-based analysis with and without smoothing, two types of region-based analysis, and combinations thereof with skeletonization. The templates included a study-specific template created with DTI-TK and the IIT template serving as a standard template. To control for other factors in the pipeline, the experiments used a common dataset, acquired at 1.5T with a single shell high angular resolution diffusion MR imaging protocol, and tensor-based spatial normalization with DTI-TK. Scan-rescan reliability was assessed using the coefficient of variation (CV) and intraclass correlation (ICC) in eight subjects with three scans each. Sensitivity to normal aging was assessed in a population of 80 subjects aged 25-65 years old, and methods were compared with respect to the anatomical agreement of significant findings and the R2 of the associated models of fractional anisotropy. The results show that reliability depended greatly on the method used for spatial mapping. The largest differences in reliability were found when adding smoothing and comparing voxel-based and region-based analyses. Skeletonization and template type were found to have either a small or negligible effect on reliability. The aging results showed agreement among the methods in nine brain areas, with some methods showing more sensitivity than others. Skeletonization and smoothing were not major factors affecting sensitivity to aging, but the standard template showed higher R2 in several conditions. A structural comparison of the templates showed that large deformations between them may be related to observed differences in patterns of significant voxels. Most areas showed significantly higher R2 with voxel-based analysis, particularly when clusters were smaller than the available regions-of-interest. Looking forward, these results can potentially help to interpret results from existing white matter imaging studies, as well as provide a resource to help in planning future studies to maximize reliability and sensitivity with regard to the scientific goals at hand.

Kernel regression estimation of fiber orientation mixtures in diffusion MRI.

We present and evaluate a method for kernel regression estimation of fiber orientations and associated volume fractions for diffusion MR tractography and population-based atlas construction in clinical imaging studies of brain white matter. This is a model-based image processing technique in which representative fiber models are estimated from collections of component fiber models in model-valued image data. This extends prior work in nonparametric image processing and multi-compartment processing to provide computational tools for image interpolation, smoothing, and fusion with fiber orientation mixtures. In contrast to related work on multi-compartment processing, this approach is based on directional measures of divergence and includes data-adaptive extensions for model selection and bilateral filtering. This is useful for reconstructing complex anatomical features in clinical datasets analyzed with the ball-and-sticks model, and our framework's data-adaptive extensions are potentially useful for general multi-compartment image processing. We experimentally evaluate our approach with both synthetic data from computational phantoms and in vivo clinical data from human subjects. With synthetic data experiments, we evaluate performance based on errors in fiber orientation, volume fraction, compartment count, and tractography-based connectivity. With in vivo data experiments, we first show improved scan-rescan reproducibility and reliability of quantitative fiber bundle metrics, including mean length, volume, streamline count, and mean volume fraction. We then demonstrate the creation of a multi-fiber tractography atlas from a population of 80 human subjects. In comparison to single tensor atlasing, our multi-fiber atlas shows more complete features of known fiber bundles and includes reconstructions of the lateral projections of the corpus callosum and complex fronto-parietal connections of the superior longitudinal fasciculus I, II, and III.

Genetic markers of cholesterol transport and gray matter diffusion: a preliminary study of the CETP I405V polymorphism.

Variations of the cholesteryl ester transfer protein polymorphism (CETP I405V/rs5882) have been associated with an increased risk for neurodegeneration, particularly when examined in conjunction with the epsilon 4 isoform of apolipoprotein E (ApoE4). Despite these identified relationships, the impact of I405V on gray matter microstructure remains unknown. The present study examined the impact of the CETP I405V polymorphism on gray matter integrity among 52 healthy adults between ages 51 and 85. Gray matter was measured bilaterally using diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Participants were grouped according to a dominant statistical model (II genotype vs. IV/VV genotypes) and secondary analyses were completed to examine the interactive effects of CETP and ApoE4 on DTI metrics. Compared to individuals with the IV/VV genotypes, II homozygotes demonstrated significantly higher MD in bilateral temporal, parietal, and occipital gray matter. Secondary analyses revealed higher FA and AD in the left temporal lobe of IV/VV genotypes with an ApoE4 allele. Our results provide preliminary evidence that CETP II homozygosity is a predisposing risk factor for gray matter abnormalities in posterior brain regions in healthy older adults, independent of an ApoE4 allele.

The spatial organization of ascending auditory pathway microstructural maturation from infancy through adolescence using a novel fiber tracking approach.

Auditory perception is established through experience-dependent stimuli exposure during sensitive developmental periods; however, little is known regarding the structural development of the central auditory pathway in humans. The present study characterized the regional developmental trajectories of the ascending auditory pathway from the brainstem to the auditory cortex from infancy through adolescence using a novel diffusion MRI-based tractography approach and along-tract analyses. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to quantify the magnitude and timing of auditory pathway microstructural maturation. We found spatially varying patterns of white matter maturation along the length of the tract, with inferior brainstem regions developing earlier than thalamocortical projections and left hemisphere tracts developing earlier than the right. These results help to characterize the processes that give rise to functional auditory processing and may provide a baseline for detecting abnormal development.

Spatiotemporal patterns of cortical microstructural maturation in children and adolescents with diffusion MRI.

Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. This study characterized cortical microstructural maturation using diffusion MRI (fwe-DTI and NODDI multi-compartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased and fwe-DTI metrics decreased with age. Using non-negative matrix factorization, we found cortical regions that correspond to lower-order sensory regions mature earlier than higher-order association regions. Our findings corroborate previous histological and neuroimaging studies that show spatially-varying patterns of cortical maturation that may reflect unique developmental processes of cytoarchitectonically-determined regional patterns of change.

Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging.

Background: Traumatic brain injury (TBI) can alter brain structure and lead to onset of persistent neuropsychological symptoms. This study investigates the relationship between brain injury and psychological distress after mild TBI using multimodal magnetic resonance imaging. Methods: A total of 89 patients with mild TBI from the TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) pilot study were included. Subscales of the Brief Symptoms Inventory 18 for depression, anxiety, and somatization were used as outcome measures of psychological distress approximately 6 months after the traumatic event. Glasgow Coma Scale scores were used to evaluate recovery. Magnetic resonance imaging data were acquired within 2 weeks after injury. Perivascular spaces (PVSs) were segmented using an enhanced PVS segmentation method, and the volume fraction was calculated for the whole brain and white matter regions. Cortical thickness and gray matter structures volumes were calculated in FreeSurfer; diffusion imaging indices and multifiber tracts were extracted using the Quantitative Imaging Toolkit. The analysis was performed considering age, sex, intracranial volume, educational attainment, and improvement level upon discharge as covariates. Results: PVS fractions in the posterior cingulate, fusiform, and postcentral areas were found to be associated with somatization symptoms. Depression, anxiety, and somatization symptoms were associated with the cortical thickness of the frontal-opercularis and occipital pole, putamen and amygdala volumes, and corticospinal tract and superior thalamic radiation. Analyses were also performed on the two hemispheres separately to explore lateralization. Conclusions: This study shows how PVS, cortical, and microstructural changes can predict the onset of depression, anxiety, and somatization symptoms in patients with mild TBI.

FMRI Complexity Correlates with Tau-PET and Cognitive Decline in Late-Onset and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Neurofibrillary tangle pathology detected with tau-PET correlates closely with neuronal injury and cognitive symptoms in Alzheimer's disease (AD). Complexity of rs-fMRI has been demonstrated to decrease with cognitive decline in AD. OBJECTIVE: We hypothesize that the rs-fMRI complexity provides an index for tau-related neuronal injury and cognitive decline in the AD process. METHODS: Data was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI3) and the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) study. Associations between tau-PET and rs-fMRI complexity were calculated. Potential pathways relating complexity to cognitive function mediated through tau-PET were assessed by path analysis. RESULTS: We found significant negative correlations between rs-fMRI complexity and tau-PET in medial temporal lobe of both cohorts, and associations of rs-fMRI complexity with cognitive scores were mediated through tau-PET. CONCLUSION: The association of rs-fMRI complexity with tau-PET and cognition, suggests that a reduction in complexity is indicative of tau-related neuropathology and cognitive decline in AD processes.