Biology subjects

Gee, D. G.

Publications and source records attributed to Gee, D. G..

6 recordsLinked to original sources

bioRxiv2025

Corticolimbic structure-function coupling is sensitive to childhood adversity and buffers adversity-related symptoms during development

Childhood adversity is a potent predictor of mental health problems across the lifespan, and a rich cross-species literature implicates stress-sensitive corticolimbic circuits in adversity-related psychopathology. Structure-function coupling (SFC) is a promising multimodal marker that is sensitive to developmental plasticity. While emerging evidence suggests cortical SFC is sensitive to adversity exposure during early childhood, it is unknown how SFC in stress-sensitive corticolimbic circuits links adversity exposure with mental health across development. We examined associations between adversity exposure, transdiagnostic symptomatology, and both amygdala-cortical and hippocampal-cortical SFC across development in a large sample of youth (N = 607, 39% F). Results revealed that adversity exposure moderated age-related change in amygdala-vmPFC SFC (p = .007), such that youth exposed to higher, but not lower, levels of adversity showed an age-related increase in amygdala-vmPFC SFC. Further, amygdala-vmPFC SFC buffered the effect of adversity on internalizing symptoms (p = .012), such that those youth with higher adversity exposure who had stronger amygdala-vmPFC SFC also displayed lower internalizing symptoms. Separately, higher adversity exposure was associated with lower hippocampal-limbic network SFC (p = .037), which moderated the effect of adversity on internalizing symptoms (p = .010). These findings highlight that structural and functional neurodevelopment of amygdala-vmPFC and hippocampal-limbic network connections may adapt in distinct ways to support mental health following adversity, with implications for risk and resilience against internalizing psychopathology. Significance StatementDelineating how childhood adversity alters neurodevelopment is critical to understanding the origins of adversity-related risk for mental health disorders. Here, we leverage a multimodal marker of the correspondence between brain structure and function to test how corticolimbic circuits are jointly shaped by adversity exposure. Results reveal that the structure-function coupling of amygdala-vmPFC and hippocampal-limbic networks is associated with adversity exposure and differentially moderate risk for internalizing psychopathology. These findings suggest key roles for neural stress regulation and memory circuits in adapting to support optimal functioning following adversity exposure, and highlight the concordance of neural structure and function as an important indicator of individual-level risk and resilience.

neuroscience↗

bioRxiv2024

Transdiagnostic Symptom Domains are Associated with Head Motion During Multimodal Imaging in Children

BackgroundHead motion is a challenge for neuroimaging research in developmental populations. However, it is unclear how transdiagnostic symptom domains including attention, disruptive behavior (e.g., externalizing behavior), and internalizing problems are linked to scanner motion in children, particularly across structural and functional MRI. The current study examined whether transdiagnostic domains of attention, disruptive behavior, and internalizing symptoms are associated with scanner motion in children during multimodal imaging. MethodsIn a sample of 9,045 children aged 9-10 years in the Adolescent Brain Cognitive Development (ABCD) Study, logistic regression and linear mixed-effects models were used to examine associations between motion and behavior. Motion was indexed using ABCD Study quality control metrics and mean framewise displacement for the following: T1-weighted structural, resting-state fMRI, diffusion MRI, Stop-Signal Task, Monetary Incentive Delay task, and Emotional n-Back task. The Child Behavior Checklist was used as a continuous measure of symptom severity. ResultsGreater attention and disruptive behavior problem severity was associated with a lower likelihood of passing motion quality control across several imaging modalities. In contrast, increased internalizing severity was associated with a higher likelihood of passing motion quality control. Increased attention and disruptive behavior problem severity was also associated with increased mean motion, whereas increased internalizing problem severity was associated with decreased mean motion. ConclusionTransdiagnostic domains emerged as predictors of motion in youths. These findings have implications for advancing development of generalizable and robust brain-based biomarkers, computational approaches for mitigating motion effects, and enhancing accessibility of imaging protocols for children with varying symptom severities.

neuroscience↗

bioRxiv2024

Variation in moment-to-moment brain state engagement changes across development and contributes to individual differences in executive function

Neural variability, or variation in brain signals, facilitates dynamic brain responses to ongoing demands. This flexibility is important during development from childhood to young adulthood, a period characterized by rapid changes in experience. However, little is known about how variability in the engagement of recurring brain states changes during development. Such investigations would require the continuous assessment of multiple brain states concurrently. Here, we leverage a new computational framework to study state engagement variability (SEV) during development. A consistent pattern of SEV changing with age was identified across cross-sectional and longitudinal datasets (N>3000). SEV developmental trajectories stabilize around mid-adolescence, with timing varying by sex and brain state. SEV successfully predicts executive function (EF) in youths from an independent dataset. Worse EF is further linked to alterations in SEV development. These converging findings suggest SEV changes over development, allowing individuals to flexibly recruit various brain states to meet evolving needs.

neuroscience↗

bioRxiv2023

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

neuroscience↗

bioRxiv2021

Age-related change in task-evoked amygdala-prefrontal circuitry: a multiverse approach with an accelerated longitudinal cohort aged 4-22 years

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed - perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala-mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years- old; N=98; 183 scans; 1-3 scans/participant). Participants, recruited from the greater Los Angeles area, completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala-mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala--mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala-mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results. (Preprint: https://www.biorxiv.org/content/10.1101/2021.10.08.463601v1). Key PointsO_LIMultiverse analyses applied to fMRI data are valuable for determining the robustness of findings to varied analytical choices C_LIO_LIIn the current study, age-related change estimates for amygdala reactivity were relatively robust to analytical decisions, though gPPI functional connectivity analyses were much more sensitive, leading some estimates to flip sign C_LIO_LIBoth test-retest reliability and robustness to analytical choices are important considerations for developmental research C_LI

neuroscience↗

bioRxiv2020

Decomposing complex links between the childhood environment and brain structure in school-aged youth

Childhood experiences play a profound role in conferring risk and resilience for brain and behavioral development. However, how different facets of the environment shape neurodevelopment remains largely unknown. Here we sought to decompose heterogeneous relationships between environmental factors and brain structure in 989 school-aged children from the Adolescent Brain Cognitive Development Study. We applied a cross-modal integration and clustering approach called Similarity Network Fusion, which combined two brain morphometrics (i.e., cortical thickness and myelin-surrogate markers), and key environmental factors (i.e., trauma exposure, neighborhood safety, school environment, and family environment) to identify homogeneous subtypes. Depending on the subtyping resolution, results identified two or five subgroups, each characterized by distinct brain structure-environment profiles. Notably, more supportive caregiving and school environments were associated with increased myelination, whereas less supportive caregiving, higher family conflict and psychopathology, and higher perceived neighborhood safety were observed with increased cortical thickness. These subtypes were highly reproducible and predicted externalizing symptoms and overall mental health problems. Our findings support the theory that distinct environmental exposures differentially influence neurodevelopment. Delineating more precise associations between risk factors, protective factors, and brain development may inform approaches to enhance risk identification and optimize interventions targeting specific experiences.

neuroscience↗