Biology subjects

Herting, M. M.

Publications and source records attributed to Herting, M. M..

At least 19 recordsLinked to original sources

bioRxiv2026

Dual ecological-cultural pathways of sociocultural environment and resting state functional connectivity among Hispanic adolescents in the ABCD Study

Hispanic Americans face persistent health disparities rooted in complex sociocultural and bioecodevelopmental dynamics. Identifying early neurodevelopmental trajectories that confer risk or resilience during adolescence is critical for developing targeted health equity interventions. Grounded in the NIMHD Research Framework and bioecodevelopmental theory, data from 12- to 14-year-old Hispanic adolescents in the Adolescent Brain Cognitive Development (ABCD) Study were analyzed (n=236). Partial least squares correlation (PLSC) was used to evaluate multivariate associations between sociocultural measures, spanning individual, family, and community levels, and resting-state functional connectivity (rsFC) networks. Post hoc linear mixed-effects models examined how derived sociocultural-rsFC patterns predicted measures of physical and mental health, linking bioecodevelopmental patterns to adolescent well-being. PLSC revealed dual community- and family-level neural pathways of biological embedding, diverging from traditional nested bioecodevelopmental assumptions. The community pathway linked child opportunity and neighborhood disadvantage to connectivity across Cingulo-Opercular, Default, Dorsal Attention, Visual Networks. This community-rsFC profile was associated with lower respiratory functioning, reflecting an allostatic load marker of environmental stress. The family pathway linked caregiver ethnic identity and heritage acculturation to Default, Ventral Attention, Sensorimotor-Mouth, and Visual Networks connectivity, suggesting that the family system shapes neural systems underlying social attunement and identity formation. Structural community factors and familial culture impose distinct neurobiological demands on the adolescent connectome among Hispanic youth. Findings highlight respiratory health as a biological marker of environmental adversity and underscore the necessity of structural and culturally sustaining interventions to promote health equity among Hispanic youth.

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bioRxiv2026

Prefrontal working memory activity partially mediates link between enriched neighborhood environments and episodic memory among 9-13-year-olds

BackgroundEnriched environments support neurodevelopment. The pathways linking enrichment to cognitive processes such as episodic memory among youth remain unclear. This study examined whether brain function and structure in episodic memory-implicated neurocircuitry mediate the relationship between neighborhood enrichment and episodic memory performance. MethodsWe analyzed data from the Adolescent Brain Cognitive Development Study (n = 9,028) at two timepoints (baseline: 9-11-years-old and two-year follow-up: 11-13-years-old). Neighborhood enrichment was estimated at the childs primary residential address proxied by the Child Opportunity Index 2.0 (COI). Episodic memory was assessed using the Picture Sequence Memory Test (PSMT). A multimodal neuroimaging approach examined task-based working memory-related functional activity, brain volume, and resting-state intrinsic activity in 26 bilateral brain regions, segmented using the Desikan-Killiany atlas, implicated in episodic memory. Following FDR-corrected linear mixed effects models, controlling for sociodemographic, neuroimaging factors, and site-related variability, two sets of mediation analyses were conducted per time point. ResultsGreater neighborhood enrichment (i.e., higher COI scores) was directly associated with better episodic memory, prefrontal cortex (PFC) task-based functional activity, and larger PFC and medial temporal lobe volume across timepoints. PFC task-based functional activity, but not brain volume or intrinsic activity, partially mediated these relationships. Specifically, PFC task-activity in the left and right caudal and rostral middle frontal gyri, and left pars opercularis, accounted for [~]2-7% of the mediated effect. ConclusionOur findings contribute to a rapidly growing body of literature linking environmental influences on neurocognitive outcomes during development. Given childhood and adolescence represent sensitive periods for neurodevelopment, interventions aimed at increasing neighborhood access to enriching experiences such as educational opportunities, cognitively stimulating activities, and social support may have lasting benefits for neurocognitive development.

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bioRxiv2025

Oestradiol and Progesterone Variability in Adolescent Females: Associations with Brain Structure and Mental Health Problems

ObjectiveAdolescent females are at increased risk for adverse mental health problems, and puberty is thought to be a critical factor. Pubertal onset involves substantial variability in oestradiol (E2) and progesterone (P4), yet the impact of these hormone dynamics remains unclear. We investigated whether within-individual E2 and P4 variability across one month relates to brain structure and mental health problems in adolescent females. MethodsParticipants were 147 females (11-17 years) from the community-based, cross-sectional Puberty and NeuroDevelopment in Adolescents (PANDA) study in Australia. Salivary E2 and P4 were collected weekly for one month, with variability indexed as within-subject standard deviation. Structural MRI was acquired on the final sampling day. Mental health problems were assessed via self- and parent-report. Linear regression and mediation analyses tested associations between hormone variability, brain structure, and mental health, adjusting for demographics. ResultsGreater P4 variability was associated with smaller left thalamus volume (Cohens d = -0.26, pFDR = 0.031). Higher E2 variability was associated with fewer anxiety (d = -0.170, pFDR = 0.043) and depressive symptoms (d = -0.179, pFDR = 0.036), lower emotion dysregulation (d = -0.179, pFDR = 0.036), and smaller right hippocampus volume in pre-menarchal adolescents (d = -0.192, p = 0.02). Weekly reductions in E2 predicted lower positive affect (d = 0.084, p = 0.048). ConclusionThese findings indicate that hormone variability may meaningfully shape brain and behavioural development in adolescent girls differently from hormone-related transitions in adulthood. Larger, replicable, and longer-term studies are needed to confirm these patterns. Oestradiol and Progesterone Variability in Adolescent Females: Associations with Brain Structure and Mental Health Problems. Muskan Khetan 1, Ye Ella Tian 2, Nandita Vijayakumar 3,4, Sarah Whittle 1,4 O_LICentre for Youth Mental Health, University of Melbourne, Australia C_LIO_LIDepartment of Psychiatry, University of Melbourne, Australia C_LIO_LIMurdoch Childrens Research Institute, Australia C_LIO_LISchool of Psychology, Deakin University, Australia C_LI

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bioRxiv2025

Outdoor Air Pollution, Perivascular Space Morphology, and Cognition in Preadolescence

BackgroundAmbient air pollution exposure is associated with structural brain differences and poorer cognition in children; however, mechanisms of toxicity remain unclear. Perivascular spaces (PVS), key for brain waste clearance, may play a role in the neurotoxicity of air pollution. This study explored associations between air pollution exposure, PVS morphology, and cognition in preadolescents. MethodsWe analyzed cross-sectional Adolescent Brain Cognitive DevelopmentSM (ABCD) Study(R) data from 6,949 9-10-year-old participants. Annual average exposures to PM2.5, O3, NO2, and 15 PM2.5 components were estimated using spatiotemporal models mapped to residential addresses. PVS count and volume were derived from T1w and T2w MRI, and cognition was estimated using NIH Toolbox scores. Linear mixed-effects models examined independent associations between air pollution, PVS, and cognition; weighted quantile sum regression assessed co-exposure effects of PM2.5 mixtures. FindingsLinear models revealed that exposures to Zn, NH4 +, and Br were positively associated with PVS count in several regions. Higher PVS count in five key regions was associated with poorer cognitive performance across several NIH Toolbox domains. Higher Ca, Zn, and NH 4 + exposures were associated with poorer cognition (PFDR < 0.01). Higher frontal lobe PVS count mediated the association between Zn exposure and poorer total cognition (P < 0.01). Co-exposure models revealed that PM2.5 mixtures were associated with higher temporal and cingulate PVS count, and poorer working memory and crystallized intelligence (P < 0.01). InterpretationOutdoor air pollution was associated with higher PVS count and reduced cognition, suggesting that brain clearance may be a novel mechanism linking pollution to neurodevelopmental harm in preadolescents. FundingThis work was supported by the National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS) (Grant Nos. R01ES032295 and R01ES031074 [to MMH]; T32ES013678 [to JM]; P30ES07048 [to JM and MAR]; 3P30ES000002-55S [to MAR]), National Institute of Mental Health (NIMH) (Grant RF1MH123223 [to JC]), National Institute of Neurological Disorders and Stroke (Grant R01NS128486 [to JC]), and EPA grants (Grant Nos. 83587201 and 83544101 [to JS]).

neuroscience↗

bioRxiv2025

Sources of outdoor air pollution exposure and child brain network development across the United States

Ambient fine particulate matter (PM2.5) pollution is a heterogeneous mixture of chemicals with documented neurotoxic effects. Developmental neuroimaging literature has linked childhood PM2.5 exposure to alterations in brain morphology, microarchitecture, and function, with implications for cognition and psychopathology. However, the extant literature remains largely cross-sectional and often considers PM2.5 a single pollutant, rather than a heterogeneous mixture of chemicals from different sources. This work addresses these gaps by leveraging estimates of exposure to six PM2.5 sources derived from positive matrix factorization, and longitudinal neuroimaging data from a large, geographically-diverse sample of Adolescent Brain Cognitive Development Study youth (N = 6,291) from across the United States (U.S.). To identify exposure-related differences in brain function and assess their geographical generalizability, we used a predictive modeling approach to assess both differences in functional brain network connectivity during childhood (9-11 years of age) and changes in functional brain network connectivity during the transition to adolescence (9-13 years of age) related to PM2.5 exposure. Childhood PM2.5 exposure from traffic emissions and industrial/residual fuel burning were linked to mixed patterns of both stronger and weaker connectivity of sensorimotor networks at ages 9-11 years. Conversely, childhood exposures to secondary pollutants (i.e., ammonium sulfates, nitrates) were linked to largely stronger connectivity of brain networks underlying higher-order cognition that decreased over the following two years. However, these patterns of exposure-related functional connectivity identified in youth across the U.S. better represented youth living in the northeast as compared to youth living in the west. Altogether, this work provides insights into the neurotoxicity of outdoor air pollution exposure in developing sensory and motor systems and potential for biomarkers of eventual psychopathology.

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bioRxiv2025

Ambient Pollution Components and Sources Associated with Hippocampal Architecture and Memory in Pre-Adolescents

BackgroundAmbient air pollution poses significant risks to brain health. The hippocampus may be particularly vulnerable, yet the extent to which it is impacted in children remains unclear. MethodsUsing partial least squares correlation, we cross-sectionally analyzed air pollution, brain, and cognitive data from the Adolescent Brain Cognitive Development Study to examine how multi-pollutant exposure influences hippocampal structure and memory in 9-11-year-olds (n= 7,940). Annual average air pollution exposures included PM2.5 (total mass, 15 components, and 6 source factors), NO2, and 8-hour maximum O3. Hippocampal outcomes included microstructure measured using Restriction Spectrum Imaging and hippocampus longitudinal-axis (i.e., head, body, tail) volumes. We examined hippocampal-dependent list-learning using the Rey Auditory Verbal Learning Test. Models were adjusted for demographic, socioeconomic, and neuroimaging factors. FindingsPM2.5 total mass was associated with hippocampal microstructure, but not long-axis volume or list-learning ability. Component and source analyses provided greater specificity: higher bromine, sulfate, and vanadium exposure was related to microstructure (72% shared variance), while higher copper and zinc exposure correlated with smaller left head and right body and tail volumes (75% shared variance). Source models implicated biomass burning and traffic pollution in microstructure (61% and 32% shared variance) and industrial and traffic sources in smaller hippocampal volumes (77% shared variance). Higher exposure to several components were also linked to poorer list-learning (67% shared variance). DiscussionCo-exposure to multiple pollutants is linked to differences in hippocampal structure and memory, showing that associations are driven not only by PM2.5 total mass but also by specific components and sources. This evidence underscores the necessity of targeting source-specific (e.g., biomass burning, traffic, and industrial emissions) and constituent components (e.g., metals) of air pollution during critical developmental windows to safeguard brain health.

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bioRxiv2025

Sex-specific Effects of Outdoor Air Pollution on Subcortical Microstructure and Weight Gain: Findings from the ABCD Study

Obesity is associated with structural alterations of brain regions that support eating behavior. Exposure to air pollutants might exacerbate this association through neurotoxic effects on the brain. This study evaluated whether air pollution exposure 9-10 years old children, coupled with brain microstructure development in appetite-regulating regions, is associated with body mass index (BMI) changes over two years, and whether these associations differ by sex. Data were gathered from the Adolescent Brain Cognitive Development Study(R) (nbaseline=4,802, ages=9-10, males=49.9%, nfollow-up=2,439, ages=11-12, males=51.1%). Annual average estimates of ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), ground-level ozone (O3), and redox-weighted oxidative capacity (Oxwt, a joint measure of NO2 and O3) were gathered from youths residential addresses. Brain microstructure in 16 subcortical regions was assessed using diffusion-weighted MRI, focusing on proxies of cellular and neurite density: restricted normalized isotropic (RNI) and directional (RND) diffusion, respectively. Linear mixed-effects models examined whether air pollution and brain microstructure are related to BMI changes over two years, and whether these associations differed by sex. Exposure to PM2.5 coupled with high RND estimates in right caudate nucleus, bilateral putamen, and pallidum were associated with higher BMI over time, with pronounced effects in males (all p<0.05). PM2.5 coupled with greater neurite density in regions involved in reward-processing and decision-making were associated with higher BMI over a 2-year follow-up, especially in males. This research highlights air pollution as a modifiable risk factor for how differences in basal ganglia neurite density map onto obesity risk, with important implications for public health policy. HIGHLIGHTSO_LIHigh PM2.5 exposure and subcortical neurite density is associated with weight gain C_LIO_LIPM2.5 and subcortical development associations with BMI are pronounced in males C_LIO_LISignificant associations with BMI were found in regions involved in food intake C_LI

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bioRxiv2025

Sleep duration and efficiency moderate the effects of prenatal and childhood ambient pollutant exposure on global white matter microstructural integrity in adolescence

BackgroundAir pollution is a ubiquitous neurotoxicant associated with alterations in structural connectivity. Good habitual sleep may be an important protective lifestyle factor due to its involvement in the brain waste clearance and its bidirectional relationship with immune function. Wearable multisensory devices may provide more objective measures of sleep quantity and quality. We investigated whether sleep duration and efficiency moderated the relationship between prenatal and childhood pollutant exposure and whole-brain white matter microstructural integrity at ages 10-13 years. MethodsWe used multi-shell diffusion-weighted imaging data collected on 3T MRI scanners and objective sleep data collected with Fitbit Charge 2 from the 2-year follow-up visit for 2178 subjects in the Adolescent Brain Cognitive Development Study(R). White matter tracts were identified using a probabilistic atlas. Restriction spectrum imaging was performed to extract restricted normalized isotropic (RNI) and directional (RND) signal fraction parameters for all white matter tracts, then averaged to calculate global measures. Sleep duration was calculated by summing the time spent in each sleep stage; sleep efficiency was calculated by dividing sleep duration by time spent in bed. Using an ensemble-based modeling approach, air pollution concentrations of PM2.5, NO2, and O3 were assigned to each childs residential addresses during the prenatal period (9-month average before birthdate) as well as at ages 9- 10 years. Multi-pollutant linear mixed effects models assessed the associations between global RNI and RND and sleep-by-pollutant interactions, adjusting for appropriate covariates. ResultsSleep duration interacted with childhood NO2 exposure and sleep efficiency interacted with prenatal O3 exposure to affect RND at ages 10-13 years. Longer sleep duration and higher sleep efficiency in the context of higher pollutant exposure was associated with lower RND compared to those with similar pollutant exposure but shorter sleep duration and lower sleep efficiency. ConclusionsLow-level air pollution poses a risk to brain health in youth, and healthy sleep duration and efficiency may increase resilience to its harmful effects on white matter microstructural integrity. Future studies should evaluate the generalizability of these results in more diverse cohorts as well as utilize longitudinal data to understand how sleep may impact brain health trajectories in the context of pollution over time.

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bioRxiv2024

Pubertal hormones and the early adolescent female brain: a multimodality brain MRI study

Puberty is a critical developmental process that is associated with changes in steroid hormone levels, which are believed to influence adolescent behaviour via their effects on the developing brain. So far, there are limited and inconsistent findings regarding the relationship between steroid hormones and brain structure and function in adolescent females, with many existing studies employing small sample sizes. Thus, in this study, we explored the association between oestradiol (E2), testosterone (Tes) and dehydroepiandrosterone (DHEA) and brain structure (gray matter volume, sulcal depth, cortical thickness and white matter microstructure) and function (resting-state connectivity, emotional n-back task-related function) in 3024 adolescent females (age 8.92 - 13.33 years, mean age (SD) = 10.37 (0.94) years) from the Adolescent Brain Cognitive DevelopmentSM (ABCD(R)) Study. We used elastic-net regression with cross- validation to investigate associations between hormones and brain phenotypes derived from multiple imaging modalities. We found that structural brain features, including cortical thickness, sulcal depth, and white matter microstructure, were among the most important features associated with hormones. E2 was most strongly associated with prefrontal and premotor regions involved in working memory and emotion processing, while Tes and DHEA were most strongly associated with parietal and occipital regions involved in visuospatial functioning. All three hormones were also associated with prefrontal, temporoparietal junction and insula cortices. Thus, using an advanced methodological approach, this study suggests both unique and overlapping neural correlates of pubertal hormones in adolescent females and sheds light on the mechanisms by which puberty influences adolescent development and behaviour.

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bioRxiv2024

Effects of one-night partial sleep deprivation on perivascular space volume fraction: Findings from the Stockholm Sleepy Brain Study

Increased waste clearance in the brain is thought to occur most readily during late-stage sleep (stage N3). Sleep deprivation disrupts time spent in deeper sleep stages, fragmenting the clearance process. Here, we have utilized the publicly available Stockholm Sleepy Brain Study to investigate whether various sleep-related measures are associated with changes in perivascular space (PVS) volume fraction following a late-night short-sleep experiment. Our sample consisted of 60 participants divided into old (65-75 years) and young (20-30 years) age groups. We found that partial sleep deprivation was not significantly associated with major PVS changes. In the centrum semiovale, we observed an interaction between percentage of total sleep time spent in N3 and sleep deprivation status on PVS volume fraction. In the basal ganglia, we saw an interaction between N2 (both percentage of total sleep time and absolute time in minutes) and sleep deprivation status. However, the significance of these findings did not survive multiple comparisons corrections. This work highlights the need for future longitudinal studies of PVS and sleep, allowing for quantification of within-subject morphological changes occurring in PVS due to patterns of poor sleep. Our findings here provide insight on the impacts that a single night of late-night short-sleep has on the perivascular waste clearance system. Statement of SignificanceSleep issues have been known to be associated with a variety of health risks. Recent research has shown the importance of sleep for brain clearance, with increases in brain clearance occurring during sleep. PVS seen on MRI are known to represent both influx and efflux pathways for the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the brain parenchyma, a key process underlying the waste clearance system.1 Numerous recent studies have found links between sleep disruption and PVS volume changes. However, no study to date has been able to examine within-subject changes in PVS resulting from experimental manipulation of sleep. Our study represents the first within-subject study looking at the effects of partial sleep deprivation on PVS volume fraction using an automated PVS segmentation technique.

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bioRxiv2024

Idiosyncrasy and generalizability of contraceptive- and hormone-related functional connectomes across the menstrual cycle

Neuroendocrinology has received little attention in human neuroscience research, resulting in a dearth of knowledge surrounding potent and dynamic modulators of cognition and behavior, as well as brain structure and function. This work addresses one such phenomenon by studying functional connectomics related to ovarian hormone fluctuations throughout the adult menstrual cycle. To do so, we used functional magnetic resonance imaging (fMRI) and hormone assessments from two dense, longitudinal datasets to assess variations in functional connectivity with respect to endogenous and exogenous endocrine factors throughout the menstrual cycle. First, we replicated prior findings that common, group-level and individual specific factors have similar relative contributions to functional brain network organization. Second, we found widespread connectivity related to hormonal contraceptive (HC) use, in addition to sparser estradiol- and progesterone-related connectivity, and differential generalizability of these subnetworks that suggests progestin-specific impacts on functional connectivity in HC users. These results provide novel insight into within-individual changes in brain organization across the menstrual cycle and the extent to which these changes are shared between individuals, illuminating understudied phenomena in reproductive health and important information for all neuroimaging studies that include participants who menstruate. Author SummaryEndocrine modulation of brain function across the menstrual cycle is poorly understood. Human neuroimaging research on the menstrual cycle has long relied on group- and or coarse, within-individual cycle stage-differences, overlooking considerable individual differences in brain organization, the menstrual cycle, and hormone concentrations. Here, we take a multi-dataset approach to identify idiosyncratic contraceptive- and hormone-related functional connectivity from within-individual neuroendocrine dynamics and then test the generalizability of this connectivity to other individuals. In doing so, we identified idiosyncratic hormone-responsive subnetworks that are somewhat generalizable to other individuals, though this generalizability is complicated by hormonal contraceptive use, potentially reflecting differential connectivity between contraceptive formulations. Thus, this work illuminates individual similarities and differences in neuroendocrine dynamics across the menstrual cycle.

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bioRxiv2024

More similarity than difference: comparison of within- and between-sex variance in early adolescent brain structure

BackgroundAdolescent neuroimaging studies of sex differences in the human brain predominantly examine mean differences between males and females. This focus on between-groups differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain. MethodsWe aimed to characterize the variance in brain macro-and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=7,723). Specifically, for global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within-and between-sex variance, overlap between male and female distributions, inhomogeneity of variance via the Fligner-Killeen test, and an analysis of similarities (ANOSIM). For completeness, we examined these sex differences using both uncorrected (raw) brain estimates and residualized brain estimates after using mixed-effects modeling to account for age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable. ResultsThe overlap between male and female distributions was universally greater than the difference (overlap coefficient range: 0.585 -0.985) and the ratio of within-sex and between-sex differences was similar (ANOSIM R range: -0.001 -0.117). All cortical and subcortical volumes showed significant inhomogeneity of variance, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Inhomogeneity of variance was reduced after accounting for other sources of variance. Overlap coefficients were larger and ANOSIM R values were smaller for residualized outcomes, indicating greater within-and smaller between-sex differences once accounting for other covariates. ConclusionsReported sex differences in early adolescent human brain structure may be driven by disparities in variance, rather than binary, sex-based phenotypes. Contrary to the popular view of the brain as sexually dimorphic, we found more similarity than difference between sexes in all global and regional measurements of brain structure examined. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure. HighlightsO_LIHigh male/female overlap is ubiquitous across all brain features in early adolescence C_LIO_LIMale variance exceeded female variance for global and regional brain volumes C_LIO_LIBetween-and within-sex differences were similar in magnitude for all features C_LI Plain English SummaryBrain imaging research has consistently revealed differences between males and females in the shape and size of adolescent brains. Studies usually compare the average male brain to the average female brain. However, brain structure varies greatly among individuals, even within the same sex. Without looking at both the variability within people of the same sex, and the degree of similarity between the sexes, it is unclear if separating adolescent brains into male and female categories will help us understand brain development. In this study, we looked at the overlap in brain structure among male and female youths (ages 9 to 11 years). We also compared variability between sexes and within each sex. Overall, we found that, there was more similarity than difference between male and female brains. The difference between any given male and any given female was similar to the difference between two individuals of the same sex. These findings suggest that, despite some small average differences, the brains of early adolescent males and females are more alike than different at ages 9-11 years.

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bioRxiv2024

Spatiotemporal patterns in cortical development: Age, puberty, and individual variability from 9 to 13 years of age

Humans and nonhuman primate studies suggest that timing and tempo of cortical development varies neuroanatomically along a sensorimotor-to-association (S-A) axis. Prior human studies have reported a principal S-A axis across various modalities, but largely rely on cross-sectional samples with wide age-ranges. Here, we investigate developmental changes and individual variability in cortical organization along the S-A axis between the ages of 9-13 years using a large, longitudinal sample (N = 2487-3747, 46-50% female) from the Adolescent Brain Cognitive Development Study (ABCD Study(R)). This work assesses multiple aspects of neurodevelopment indexed by changes in cortical thickness, cortical microarchitecture, and resting-state functional fluctuations. First, we evaluated S-A organization in age-related changes and, then, computed individual-level S-A alignment in brain changes and assessing differences therein due to age, sex, and puberty. Varying degrees of linear and quadratic age-related brain changes were identified along the S-A axis. Yet, these patterns of cortical development were overshadowed by considerable individual variability in S-A alignment. Even within individuals, there was little correspondence between S-A patterning across the different aspects of neurodevelopment investigated (i.e., cortical morphology, microarchitecture, function). Some of the individual variation in developmental patterning of cortical morphology and microarchitecture was explained by age, sex, and pubertal development. Altogether, this work contextualizes prior findings that regional age differences do progress along an S-A axis at a group level, while highlighting broad variation in developmental change between individuals and between aspects of cortical development, in part due to sex and puberty. Significance StatementUnderstanding normative patterns of adolescent brain change, and individual variability therein, is crucial for disentangling healthy and abnormal development. We used longitudinal human neuroimaging data to study several aspects of neurodevelopment during early adolescence and assessed their organization along a sensorimotor-to-association (S-A) axis across the cerebral cortex. Age differences in brain changes were linear and curvilinear along this S-A axis. However, individual-level sensorimotor-association alignment varied considerably, driven in part by differences in age, sex, and pubertal development.

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bioRxiv2022

Profiling intra- and inter-individual differences in child and adolescent brain development

As we move toward population-level developmental neuroscience, understanding intra- and inter-individual variability in brain maturation and sources of neurodevelopmental heterogeneity becomes paramount. Large-scale, longitudinal neuroimaging studies have uncovered group-level neurodevelopmental trajectories, and while recent work has begun to untangle intra- and inter-individual differences, they remain largely unclear. Here, we aim to quantify both intra- and inter-individual variability across facets of neurodevelopment across early adolescence (ages 8.92 to 13.83 years) in the Adolescent Brain Cognitive Development (ABCD) Study and examine inter-individual variability as a function of age, sex, and puberty. Our results provide novel insight into differences in annualized percent change in macrostructure, microstructure, and functional brain development from ages 9-13 years old. These findings reveal moderate age-related intra-individual change, but age-related differences in inter-individual variability only in a few measures of cortical macro- and microstructure development. Greater inter-individual variability in brain development were seen in mid-pubertal individuals, except for a few aspects of white matter development that were more variable between prepubertal individuals in some tracts. Although both sexes contributed to inter-individual differences in macrostructure and functional development in a few regions of the brain, we found limited support for hypotheses regarding greater male-than-female variability. This work highlights pockets of individual variability across facets of early adolescent brain development, while also highlighting regional differences in heterogeneity to facilitate future investigations in quantifying and probing nuances in normative development, and deviations therefrom.

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bioRxiv2022

Longitudinal assessment of brain structure and behavior in youth with rapid weight gain: Potential contributing causes and consequences

ObjectiveIndependent of weight status, rapid weight gain has been associated with underlying brain structure variation in regions associated with food intake and impulsivity among pre-adolescents. Yet, we lack clarity on how developmental maturation coincides with rapid weight gain and weight stability. MethodsWe identified brain predictors of two-year rapid weight gain and its longitudinal effects on brain structure and impulsivity in the Adolescent Brain Cognitive DevelopmentSM Study(R). Youth were categorized as Healthy Weight/Weight Stable (WSHW, n=225) or Weight Gainers (WG, n=221, >38lbs); 63% of the WG group were healthy weight at 9-to-10-years-old. ResultsA five-fold cross-validated logistic elastic-net regression revealed that rapid weight gain was associated with structural variation amongst 39 brain features at 9-to-10-years-old in regions involved with executive functioning, appetitive control, and reward sensitivity. Two years later, WG youth showed differences in change over time in several of these regions and performed worse on measures of impulsivity. ConclusionsThese findings suggest that brain structure in pre-adolescence may predispose some to rapid weight gain and that weight gain itself may alter maturational brain change in regions important for food intake and impulsivity. Behavioral interventions that target inhibitory control may improve trajectories of brain maturation and facilitate healthier behaviors.

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bioRxiv2021

Adolescent to young adult longitudinal development of subcortical volumes in two European sites with four waves

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age-related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls.

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bioRxiv2019

Brain Differences in the Prefrontal Cortex, Amygdala, and Hippocampus in Youth with Congenital Adrenal Hyperplasia

ContextClassical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain.\n\nObjectiveTo characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compared to age- and sex-matched controls.\n\nDesignA cross-sectional study of 27 CAH youth (16 female; 12.6 {+/-} 3.4 year) and 35 typically developing, age- and sex-matched healthy controls (20 female; 13.0 {+/-} 2.8 year) with 3-T magnetic resonance imaging scans. Brain volumes of interest included bilateral prefrontal cortex, and eight amygdala and six hippocampal subregions. Between-subject effects of group (CAH vs control) and sex, and their interaction (group-by-sex) on brain volumes were studied, while controlling for intracranial volume (ICV) and group differences in body mass index and bone age.\n\nResultsCAH youth had smaller ICV and increased cerebrospinal fluid volume compared to controls. In fully-adjusted models, CAH youth had smaller bilateral, superior and caudal middle frontal volumes, and smaller left lateral orbito-frontal volumes compared to controls. Medial temporal lobe analyses revealed the left hippocampus was smaller in fully-adjusted models. CAH youth also had significantly smaller lateral nucleus of the amygdala and hippocampal subiculum and CA1 subregions.\n\nConclusionsThis study replicates previous findings of smaller medial temporal lobe volumes in CAH patients, and suggests that lateral nucleus of the amygdala, as well as subiculum and subfield CA1 of the hippocampus are the most affected regions in CAH youth.\n\nPrecisWe collected brain scans of 27 youth with classical CAH and 35 healthy controls. Portions of the prefrontal cortex, amygdala, and hippocampus were smaller in CAH youth compared to controls.\n\nDisclosure SummaryMEG receives grant support from Novo Nordisk; consultant fees from Daiichi Sankyo, Ferring, Novo Nordisk, Nutrition & Growth Solutions, Pfizer, Sandoz, and Spruce Biosciences; serves on data safety monitoring boards for Ascendis, Millendo, and Tolmar; and receives royalties from McGraw-Hill and UpToDate.

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bioRxiv2019

Restructuring of amygdala subregion apportion across adolescence

Total amygdala volumes develop in association with sex and puberty, and postmortem studies find neuronal numbers increase in a nuclei specific fashion across development. Thus, amygdala subregions and composition may evolve with age. Our goal was to examine if amygdala subregion absolute volumes and/or relative proportion varies as a function of age, sex, or puberty in a large sample of typically developing adolescents (N=408, 43% female, 10-17 years). Utilizing the in vivo CIT168 atlas, we quantified 9 subregions and implemented Generalized Additive Mixed Models to capture potential non-linear associations with age and pubertal status between sexes. Only males showed significant age associations with the basolateral ventral and paralaminar subdivision (BLVPL), central nucleus (CEN), and amygdala transition area (ATA). Again, only males showed relative differences in the proportion of the BLVPL, CEN, ATA, along with lateral (LA) and amygdalostriatal transition area (ASTA), with age. Using a best-fit modeling approach, age, and not puberty, was found to drive these associations. The results suggest that amygdala subregions show unique developmental patterns with age in males across adolescence. Future research is warranted to determine if our findings may contribute to sex differences in mental health that emerge across adolescence.

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