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Herting, M.

Publications and source records attributed to Herting, M..

16 recordsLinked to original sources

Cortical microarchitecture supports preadolescent functional brain network connectivity

A century ago, Brodmann suggested that local cortical microarchitecture dictates function, yet modern structure-function mapping overwhelmingly focuses on white matter macroarchitecture. Here, we reframe structure-function coupling by linking gray matter microarchitecture and macroscale connectomics, demonstrating how gray matter cellular and neurite density are linked to functional network organization in preadolescents. By applying partial least squares correlation to cortical microarchitecture (i.e., cellular and neurite density) estimates from diffusion MRI and network connectivity estimates from functional MRI, in 6,320 children ages 9-11 years from the U.S.-wide Adolescent Brain Cognitive Development (ABCD) Study, we identified several principles of structure-function coupling. First, we found that functional connectivity is associated with one dominant and global pattern of cellular density differences explaining nearly 80% of shared variance, but by several patterns of neurite density differences. Second, we found similar gradients of sensorimotor network connectivity related to this dominant cellular density pattern and the secondary, rostro-caudal neurite density pattern (explaining 17% of shared variance). Third, we found a profile of attention network connectivity associated with the primary neurite density pattern (44% of shared variance) and the secondary, rostro-caudal cellular density pattern (5% of shared variance). Altogether, this work suggests that cellular density (i.e., neuronal cell bodies, support cells) across cortex largely supports a sensorimotor network connectivity gradient. Conversely, there are several connectivity-related patterns of neurite density (i.e., axons, dendrites) across cortex, providing a glimpse into how local neurite connectivity may differentially support long-range functional connectivity of sensorimotor networks and attention networks.

neuroscience↗

Air Pollution, Early Adversity, and Amygdala: Environmental Correlates of Psychopathology in Preadolescents

Early life adversity (ELA) and ambient fine particulate matter (PM2.5) are hypothesized to be environmental risk factors for altered brain structure and psychopathology, but their unique and interactive effects in childhood remain unclear. This study examines the interactive associations of ELA and annual average residential PM2.5 exposure (total mass and 15 components) on total amygdala and basolateral amygdala subregion volumes and psychopathology symptoms in a subset of children (N=3,601, 45% assigned female at birth, 9-10 years) from the Adolescent Brain Cognitive Development Study. Linear mixed-effects models, adjusting for sociodemographic factors, co-pollutants, and neuroimaging covariates, showed that ELA was associated with greater bifactor model-defined general, specific internalizing, and specific externalizing symptoms of psychopathology. PM2.5 moderated ELA associations with specific externalizing symptoms, with greater symptoms in those exposed to higher ELA and higher PM2.5 exposures. Among youth with higher ELA, smaller basolateral paralaminar volumes were linked to greater general and specific externalizing symptoms. These findings underscore the importance of considering psychosocial and physical environmental co-exposures when identifying children at risk for psychopathology.

neuroscience↗

Genetic Architecture of Perivascular Space Morphology in the Pediatric Brain

IntroductionPerivascular spaces (PVS) support brain homeostasis through metabolite delivery and waste clearance, yet the genetic determinants of PVS morphology during childhood remain unknown. Here, we leveraged cross-sectional Adolescent Brain Cognitive Development Study data (N = 6,600; ages 9-10), including genomics and 3T structural MRI. MethodsLinear mixed-effects models examined associations between 45 single nucleotide polymorphisms (SNPs) previously linked to adult PVS structure or function and PVS count and volume fraction (VF) across six macroregions and 28 Desikan-Killiany subregions. ResultsFifteen SNPs demonstrated significant associations with PVS macroregion morphology, predominantly VF; 21 SNPs demonstrated associations with subregion morphology. Variants near SLC13A3 showed the strongest, most widespread associations with PVS VF. Additional replicated variants implicated Wnt signaling, cell adhesion, apoptosis, and glymphatic function. ConclusionThese findings suggest genetic associations with PVS morphology are detectable in childhood, while highlighting developmental and regional specificity. Longitudinal studies are now needed to determine whether childhood PVS genetic architecture predicts trajectories of glymphatic maturation and associated cognitive outcomes. Key PointsO_LIPerivascular space morphology, mapped across 28 white matter subregions, displays substantial regional and interindividual variability during childhood. C_LIO_LISix genetic associations with perivascular morphology were only detectable at subregion resolution, demonstrating that lobar averaging can obscure spatially restricted signals. C_LIO_LINearly 50% of adult-identified perivascular space risk variants replicated in 9-10 year-olds, with anatomically patterned associations reflecting patterns of neurovascular complexity and neurodevelopmental timing. C_LI

neuroscience↗

Developmental Differences in White Matter Microarchitecture in Youth with ADHD: Longitudinal Findings from the ABCD Study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder and is a risk factor for later brain disorders. Here, we characterize the relationship between ADHD status and white matter cellularity across development and examine associations with medication, using a novel biophysical diffusion MRI model in youth aged 9 to 14 years. Methods: The ABCD Study(R) is a longitudinal cohort study with three biennial waves of brain MRI collection. Twenty-seven white matter tracts were delineated using multi-shell diffusion-weighted imaging (DWI) and tractography. Intracellular isotropic (RNI) and directional (RND) diffusion were quantified using the Restriction Spectrum Imaging (RSI) model. Longitudinal linear mixed-effect models characterize the effects of ADHD status and medication use on white matter cellularity across three waves. Results: By wave: 9,426 participants at baseline (mean [SD] age: 9.92 [0.63] years; 48.7% Female; 12.2% with ADHD), 6745 participants at 2-year (11.95 [0.65] years; 46.8% Female; 11.3% with ADHD), and 2,483 participants at 4-year (14.07 [0.69] years; 46.0% Female; 11.8% with ADHD). ADHD was associated with decreased RNI in 20 tracts at age 9, with evidence of developmental trajectory differences suggesting attenuation over early adolescence. We found enduring ADHD-associated decreases in RND of 16 tracts spanning ages 9 to 14 years, with methylphenidate effects on 2 tracts. Low-motion sensitivity analyses confirmed robust RNI findings, but not RND findings. ConclusionsADHD was associated with reductions in isotropic diffusion in white matter tracts, and possibly with complementary reductions in directional diffusion of select tracts. Isotropic diffusion findings suggest atypical glial cellularity in white matter during late childhood.

neuroscience↗

Patterns of brain-wide associations reflect socioeconomics

Previous brain-wide association studies (BWAS) cross-sectionally linked a specific behavioral trait, most commonly IQ or psychopathology, to variation in brain function or structure. Here, we expanded the focus of BWAS from effect sizes to interpretability and generalizability by mapping 649 variables to brain function and structure. We compared the resultant BWAS maps to other types of brain data to annotate the BWAS patterns. Socioeconomic status (SES) -- not IQ or psychopathology -- showed the strongest associations with both resting-state functional connectivity (RSFC) and cortical thickness in the Adolescent Brain Cognitive Development (ABCD) Study. A principal exposome brain pattern, anchored to sensory and motor cortex, captured 34% of the variance across all BWAS maps. This exposome pattern was strongly correlated with the SES and IQ BWAS maps and non-BWAS maps of sleep (EEG), norepinephrine (PET), and stimulants (drug trial), but not cognitive activation maps (task fMRI). Adjusting for SES, reduced brain-IQ associations by 40%. Brain with IQ associations did not generalize, as they could no longer be detected in subsamples drawn from only higher SES backgrounds, while brain with SES associations remained strong in higher-IQ-only subsamples. These findings reveal SES as the principal axis of population-level brain variation, possibly stemming from the sleep deprivation and heightened stress associated with lower SES, since socioeconomics can only indirectly affect the brain.

neuroscience↗

ADHD Medications and Preadolescent Brain Structure: Patterns of Cortical Attenuation from the ABCD Study

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in the U.S., and the stimulant and nonstimulant medications used to treat ADHD are among the most widely prescribed treatments in youth. Stimulants--including amphetamine-based (AMP) and methylphenidate-based (MPH) medications--act primarily on dopaminergic and noradrenergic systems, while nonstimulants (NS) more selectively target noradrenergic pathways. Although pharmacotherapy is the most clinically effective treatment, its neurostructural effects remain poorly understood. Leveraging the Adolescent Brain Cognitive Development* Study (ABCD Study(R)), we used a machine learning approach to identify neuroanatomical targets of medications, followed by linear mixed-effects modeling to estimate the effects of ADHD status and medication class (AMP, MPH, NS) on cortical thickness, surface area, and cortical and subcortical volumes. ADHD was not associated with statistically significant differences; however, a consistent pattern emerged in which AMP and MPH effects attenuated ADHD effects, suggesting that stimulant medications may attenuate ADHD-related cortical patterns. NS medications showed a similar, albeit weaker, effect pattern. Notably, AMP and/or MPH use was associated with significant effects in the right entorhinal cortex and the right banks of the superior temporal sulcus, potentially reflecting overcompensatory effects, as well as in the left posterior cingulate, possibly indicating de novo medication-related differences.

neuroscience↗

Sex and gender differences in perivascular space in early adolescence

Perivascular spaces (PVS) surrounding cerebral blood vessels play an important role in the blood-brain barrier and glymphatic system. Although it was once thought that PVS were either absent or too small to be seen or quantified during healthy development with MRI, recent studies have found visible, quantifiable PVS exist throughout the white matter of the cerebrum in childhood and adolescence. As a result, researchers have begun to explore individual differences, including potential sex-based variations in developing PVS. Meta-analyses in adults have shown that PVS are larger on average in males than in females, and several studies have shown a similar relationship in children. In contrast, no studies to date have examined the association between gender and PVS at any age. This cross-sectional study examined 6,538 youths from a large, nationwide sample of 9- to 11-year-olds in the U.S. to examine the relationship between sex, felt-gender, and PVS count and volume. Using a model-building approach, we conducted a series of linear mixed-effects models to determine the maximum variance explained in PVS count and volume, including age, pubertal development status, race, parent education, BMI z-score, and regional white matter volume, while also adjusting for MRI scanner and site. BMI z-score, age, and parent education were significant predictors of both PVS volume and count. Adding sex to the model improved model fit in all regions, and the further addition of felt-gender significantly improved model fit for PVS count in 5/6 regions of interest. Moreover, we found increases in PVS volume and count were associated with reduced executive function, learning, and memory. As the first study to report an association between felt-gender and PVS, our findings demonstrate the importance of considering gender in addition to sex as a potential source of structural variance in PVS in adolescents.

neuroscience↗

Estimating individual-level changes in functional brain connectivity and correspondence with topology changes

With the rise of precision medicine and large neuroimaging datasets, measuring brain changes on an individual level becomes more possible and more important. However, functional connectivity has some mathematical and conceptual quirks that make estimating individual-level changes more complicated than, for example, estimating structural brain changes. Here, we compared six different change scores, i.e., metrics for quantifying change in functional connectivity, using a large sample with two time points, roughly 2 years apart, of low-motion data from the ABCD Study (N=2,719, ages 9-13 years). First, we compared distributions and potential interpretations of each metric. Then, we assessed how well different metrics captured topology change estimates by comparing them to individual-level changes in clustering coefficient, betweenness centrality, and network strength. As multivariate metrics may be more reliable than single connections and researchers often interpret connectivity changes in topological terms, this offers additional insight into the implications of change score choice. Overall, our analyses revealed widely different distributions between change scores that conferred vastly different results and interpretations of functional connectivity changes between time points. Thus, we provide recommendations for each change score and its optimal (or suboptimal) use cases, depending on the population, study design, and research question.

neuroscience↗

Hormonal contraceptive intake during adolescence and cortical brain measures in the ABCD Study

Adolescence is a critical period in human development, marked by rapid changes in brain structure and function, influenced, in part, by sex steroids. During adolescence, females may initiate the use of hormonal contraception, which suppresses ovarian production of estradiol and progesterone. Here, we examined the impact of hormonal contraceptive use on adolescent brain structures using magnetic resonance imaging data from 1,234 individuals from the ABCD Study (average age = 14 years). We investigated differences in cortical thickness, surface area, and volume in hormonal contraceptive-users compared to non-users. Statistically significant differences were observed in several regions, and differences in cortical thickness of the paracentral gyrus survived familywise error correction. Estradiol, testosterone and DHEA levels negatively correlated with cortical thickness, surface area, and volume across both hormonal contraceptive-users and non-users only at an uncorrected threshold. These findings highlight the need to further study longitudinal effects of hormonal contraceptives and endogenous hormone changes on brain development in the ABCD Study and related datasets as these data become available.

neuroscience↗

Outdoor Air Pollution Relates to Amygdala Subregion Volume and Apportionment in Early Adolescents

BackgroundOutdoor air pollution is associated with an increased risk for psychopathology. Although the neural mechanisms remain unclear, air pollutants may impact mental health by altering limbic brain regions, such as the amygdala. Here, we examine the association between ambient air pollution exposure and amygdala subregion volumes in 9-10-year-olds. MethodsCross-sectional Adolescent Brain Cognitive DevelopmentSM (ABCD) Study(R) data from 4,473 participants (55.4% male) were leveraged. Air pollution was estimated for each participants primary residential address. Using the probabilistic CIT168 atlas, we quantified total amygdala and 9 distinct subregion volumes from T1- and T2-weighted images. First, we examined how criteria pollutants (i.e., fine particulate matter [PM2.5], nitrogen dioxide, ground-level ozone) and 15 PM2.5 components related with total amygdala volumes using linear mixed-effect (LME) regression. Next, partial least squares correlation (PLSC) analyses were implemented to identify relationships between co-exposure to criteria pollutants as well as PM2.5 components and amygdala subregion volumes. We also conducted complementary analyses to assess subregion apportionment using amygdala relative volume fractions (RVFs). ResultsNo significant associations were detected between pollutants and total amygdala volumes. Using PLSC, one latent dimension (LD) (52% variance explained) captured a positive association between calcium and several basolateral subregions. LDs were also identified for amygdala RVFs (ranging from 30% to 82% variance explained), with PM2.5 and component co-exposure associated with increases in lateral, but decreases in medial and central, RVFs. ConclusionsFine particulate and its components are linked with distinct amygdala differences, potentially playing a role in risk for adolescent mental health problems. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/617429v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@e9f2ecorg.highwire.dtl.DTLVardef@14b677forg.highwire.dtl.DTLVardef@177f8daorg.highwire.dtl.DTLVardef@172dc0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Amygdala Subregion Volumes and Apportionment in Preadolescents -- Associations with Age, Sex, and Body Mass Index

The amygdala, a key limbic structure, is critical to emotional, social, and appetitive behaviors that develop throughout adolescence. Composed of a heterogeneous group of nuclei, questions remain about potential differences in the maturation of its subregions during development. In 3,953 9- and 10-year-olds from the Adolescent Brain Cognitive DevelopmentlZI Study, the CIT168 Amygdala Atlas was used to segment nine amygdala subregions. Linear mixed-effects models were used to examine the effects of age, sex, pubertal stage, and body mass index z-score (BMIz) on subregion volumes and their relative apportionment within the amygdala. Distinct associations were observed between age, sex, and BMIz and whole amygdala volume, subregion volumes, and subregion apportionment. Pubertal stage was not related to amygdala subregion volumes. Age was associated with near-global expansion of amygdala subregions during this developmental period. Female sex was linked to smaller volumes in most amygdala subregions, with larger relative apportionment in the dorsal subregions and smaller apportionment in the basolateral ventral paralaminar subregion. Higher BMIz was associated with smaller volumes in large basolateral subregions, with increased relative apportionment in smaller subregions. These findings provide a foundational context for understanding how developmental variables influence amygdala structure, with implications for understanding future risk for brain disorders. HighlightsO_LISegmentation of amygdala subregions in nearly 4,000 preadolescents. C_LIO_LIAge, but not puberty, was associated with a near-global expansion of the amygdala. C_LIO_LISex differences exist in preadolescent amygdala apportionment. C_LIO_LIChildhood obesity is linked to differences in the basolateral amygdala. C_LI

neuroscience↗

Age-Related Decline in BBB Function is More Pronounced in Males than Females

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders. Significance statementThe blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.

neuroscience↗

Air pollution from biomass burning disrupts early adolescent cortical microarchitecture development

Exposure to outdoor particulate matter (PM2.5) represents a ubiquitous threat to human health, and particularly the neurotoxic effects of PM2.5 from multiple sources may disrupt neurodevelopment. Studies addressing neurodevelopmental implications of PM exposure have been limited by small, geographically limited samples and largely focus either on macroscale cortical morphology or postmortem histological staining and total PM mass. Here, we leverage residentially assigned exposure to six, data-driven sources of PM2.5 and neuroimaging data from the longitudinal Adolescent Brain Cognitive Development Study (ABCD Study(R)), collected from 21 different recruitment sites across the United States. To contribute an interpretable and actionable assessment of the role of air pollution in the developing brain, we identified alterations in cortical microstructure development associated with exposure to specific sources of PM2.5 using multivariate, partial least squares analyses. Specifically, average annual exposure (i.e., at ages 8-10 years) to PM2.5 from biomass burning was related to differences in neurite development across the cortex between 9 and 13 years of age. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/563430v3_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@eed0c1org.highwire.dtl.DTLVardef@cb3dbeorg.highwire.dtl.DTLVardef@1428660org.highwire.dtl.DTLVardef@8440aa_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Sex, gender diversity, and brain structure in children ages 9 to 11 years old

There remains little consensus about the relationship between sex and brain structure, particularly in childhood. Moreover, few pediatric neuroimaging studies have analyzed both sex and gender as variables of interest - many of which included small sample sizes and relied on binary definitions of gender. The current study examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9-11 years-old (N=7693). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology, including subcortical volume, cortical thickness, gyrification, and white matter microstructure. The model with sex, but not gender diversity, was the best-fitting model in 75% of gray matter regions and 79% of white matter regions examined. The addition of gender to the sex model explained significantly more variance than sex alone with regard to bilateral cerebellum volume, left precentral cortical thickness, as well as gyrification in the right superior frontal gyrus, right parahippocampal gyrus, and several regions in the left parietal lobe. For mean diffusivity in the left uncinate fasciculus, the model with sex, gender, and their interaction captured the most variance. Nonetheless, the magnitude of variance accounted for by sex was small in all cases and felt-gender score was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9-11 years-old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity. HighlightsO_LISex-related variance in regional human brain structure is widespread at ages 9-11 C_LIO_LITogether, sex and gender diversity accounted for more variance in only a few regions C_LIO_LIFelt-gender diversity itself was not significantly related to any outcome at ages 9-11 C_LIO_LIEffect sizes for sex and felt-gender estimates were small C_LI

neuroscience↗

A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study (ABCD) Cohort at Baseline

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study(R)), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index, and how these measures vary across demographic groups. This paper outlines how the physical health of the ABCD sample corresponds with that of the US population and highlights important avenues for health disparity research. This manuscript will provide important information for ABCD users and help guide analyses investigating physical health as it pertains to adolescent and young adult development.

developmental biology↗

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.\n\nHighlightsO_LIAn overview of the MRI processing pipeline for the ABCD Study\nC_LIO_LIA discussion on the challenges of large, multisite population studies\nC_LIO_LIA methodological reference for users of publicly shared data from the ABCD Study\nC_LI

neuroscience↗