Biology subjects

Parr, A. C.

Publications and source records attributed to Parr, A. C..

9 recordsLinked to original sources

bioRxiv2026

Developmental interactions between oscillatory and spontaneous neural activity support improvements in inhibitory control from adolescence into adulthood

Adolescence is a critical period of development marked by improvements in cognitive control driven by maturation of executive brain systems. Neural mechanisms supporting inhibitory control (the ability to suppress a prepotent response in favor of generating a goal-directed response) mature into adulthood in parallel with refinements in frequency-specific neural oscillations and broadband spontaneous activity, supporting more accurate and reliable performance on response inhibition tasks, such as the antisaccade oculomotor task. Prior work has established that the maturation of neural circuitry contributes to age-related decreases in spontaneous activity, supporting higher-fidelity transmission of task-relevant activity, such as frequency-specific neural oscillations, which are crucial for antisaccade performance. Using longitudinal electroencephalography (EEG) data from 146 participants (72 F, ages 10-34, 253 total sessions) collected while participants performed an antisaccade task, we sought to understand the interplay between frontal oscillatory and spontaneous activity during cognitive processing and how it supports developmental improvements in inhibitory control. We found that spontaneous activity decreased developmentally during the preparation of an inhibitory response, and that this was associated with reduced trial-to-trial variability in response latency, indicating that reductions in spontaneous activity may increase the reliability of inhibitory control processing. Furthermore, performance-related decreases in broadband spontaneous activity were associated with the suppression of preparatory high-beta oscillations in an age-dependent manner, such that this relationship became more pronounced through development. Together, these results illustrate how developmental enhancements in the coordination of frequency-specific oscillations and spontaneous activity during inhibitory response preparation support developmental improvements in inhibitory control, providing a potential mechanism through which inhibitory control becomes more accurate and reliable from adolescence into adulthood.

neuroscience↗

bioRxiv2026

Neurodevelopment of Corticostriatal Circuits and Risk for Alcohol Use During the Transition from Adolescence to Adulthood

Adolescence and early adulthood are marked by rapid neurobehavioral development in reward and decision-making processes, coinciding with the initiation and escalation of alcohol use. While adolescent and young adulthood alcohol initiation is not atypical, adult trajectories diverge: some individuals reduce or discontinue use, whereas others escalate to more frequent or problematic patterns leading to substance use disorders. Corticostriatal circuits, including the ventral striatum (nucleus accumbens; NAcc) and dorsal striatum (caudate and putamen), support reward processing, goal-directed behavior, and habit formation, and are thought to contribute to distinct stages of alcohol use. Yet, how the normative maturation of these circuits relates to alcohol initiation and the transition to habitual consumption remains unclear. We used data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence and Adulthood (NCANDA-A) cohort (822 participants, baseline ages 12 - 22 years old, 1 - 9 visits per participant, 4,356 total visits), a large multisite longitudinal neuroimaging sample spanning adolescence to young adulthood. We observed that rsfMRI functional connectivity (FC) patterns varied systematically across striatal subdivisions: NAcc FC followed an inverted U-shaped trajectory, peaking during adolescence; while caudate and putamen FC showed monotonic decreases with age. Adolescent peak NAcc connectivity was associated with alcohol use initiation, while a lack of normative decrease in putamen connectivity was linked to more frequent alcohol use in adulthood. Together, results suggest that the maturation of reward processing circuitry may support alcohol initiation, while a lack of habit system specialization may contribute to continued alcohol use, with potential implications for the timing of interventions aimed at limiting at-risk drinking.

neuroscience↗

bioRxiv2026

A Scalable fMRI Estimate of Basal Ganglia Brain Tissue Iron for Use in Developmental and Translational Neuroscience

Dopaminergic (DA) function and basal ganglia neurobiology are central to reward learning, motivation, and cognitive control, and dysregulation of these systems contributes to neuropsychiatric conditions that emerge during development. Adolescence is marked by profound reorganization of DAergic basal ganglia circuitry, yet direct in vivo assessment of the DA system remains limited in youth. Brain tissue iron is a developmentally sensitive marker of DA-related neurobiology that can be measured non-invasively via magnetic resonance imaging (MRI). Iron is an essential co-factor for DA synthesis and a foundational metabolic resource that supports cellular metabolism, myelination, and energetic demands of the basal ganglia. T2*-weighted echo-planar imaging (EPI), collected during functional MRI (fMRI), is sensitive to magnetic susceptibility of non-heme brain iron. Leveraging this property, we demonstrate the validity and broad applicability of an iron-sensitive metric that can be derived from conventional single-echo fMRI: {Delta}R2*. In a longitudinal developmental dataset (N = 151; age range 12-31), {Delta}R2* showed high reliability, strong longitudinal stability, and validity via robust convergence with established quantitative relaxometry-based iron measures (R2* and R2). Critically, {Delta}R2* can be retrospectively estimated from extant fMRI data and derived in large-scale consortium data repositories, demonstrated here in the Adolescent Brain and Cognitive Development (ABCD) baseline cohort (N = 8,366; ages 9-11). We show that {Delta}R2* captures known age-related increases in basal ganglia iron, highlighting neurodevelopmental sensitivity at population-scale. Together, these findings establish {Delta}R2* as a reliable, widely accessible marker of basal ganglia iron, enabling scalable investigation of lifespan trajectories and neuropsychiatric risk in existing and future datasets.

neuroscience↗

bioRxiv2025

Cross-species evidence for the refinement of intrinsic neural timescales supporting executive system maturation through adolescence

Brain functional, structural, and neurochemical maturation has been found to support the specialization of executive systems through adolescence that will lead to adult level processing. Importantly, animal models and initial EEG studies in humans indicate developmental improvements in neural processing of complex information that would be evident in changes in temporal dynamics, which are not well-understood. Intrinsic neural timescales (INTs), or the temporal windows over which neural populations integrate inputs, have been proposed to reflect circuit-level properties such as excitatory-inhibitory (E/I) balance, myelination, and functional properties supporting complex information processing such as in executive functioning. Here, we used a multimodal, cross-species approach to investigate how INTs develop across adolescence to support cognitive specialization. In parallel analyses using a large longitudinal human EEG cohort, adolescent intracranial sEEG recordings, and macaque local field potentials, we observed robust reductions in INTs through adolescence, particularly in frontal and parietal association cortices. These developmental reductions were shaped by local circuit physiology, as evidenced by associations between shorter INTs and both lower aperiodic exponents, indicative of increased E/I balance, and reduced spectral offsets, suggesting lower aggregate spiking. We also found structural contributions via developmental interactions between age and deep layer intracortical myelination which predicted shorter INTs, suggesting that long-range circuitry may play a key role in shaping spontaneous temporal dynamics. Functionally, shorter INTs in adolescence were linked to improved working memory accuracy and reduced response time variability, indicating a behavioral advantage of refined temporal integration windows through development. Together, these findings establish INTs as a conserved, biologically grounded signature of adolescent brain maturation, providing a mechanistic framework for how structural and physiological refinements reorganize temporal processing to support increasingly efficient cognitive function.

neuroscience↗

bioRxiv2025

Developmental variation in dopamine neurobiology, neurocognitive functioning, and impulsivity shape substance use trajectories in youth

Theoretical neurodevelopmental models implicate increases in dopamine (DA) function and limitations in neurocognitive control in risk-taking behavior, including substance use, during the transition from adolescence to adulthood. However, developmental relationships between DA, neurocognitive control, and the emergence of substance use are poorly understood. Here, we tested the role of basal ganglia tissue iron, reflecting DA neurophysiology, as well as impulsivity and inhibitory control in longitudinal developmental trajectories of substance use. We leveraged the National Consortium on Alcohol and NeuroDevelopment in Adolescence and Adulthood (NCANDA-A) cohort, a large, multisite longitudinal neuroimaging study of 807 participants (baseline ages 12 - 22 years old, 50% female, 1 - 9 annual visits per participant, 6164 sessions total). Substance use, inhibitory control, and tissue iron increased non-linearly during adolescence into young adulthood, concurrent with decreases in impulsivity. Non-linear Growth Mixture Models identified four common trajectories of substance use: low (no- or low levels of use across visits; 30% of participants), youth peak (peak use in adolescence/young adulthood followed by declines; 26%), adolescent increasing (early, steep linear increases in use from adolescence into adulthood; 17%), and adult increasing (low use in adolescence, followed by late linear increases into adulthood; 26%). We show that increased substance use was associated with a phenotype of high impulsivity, low inhibitory control, and low basal ganglia tissue iron, particularly in early adolescence in individuals who displayed youth peak patterns in substance use trajectories. These findings highlight that early developmental differences in DA-related neurobiology and associated impulsivity and cognitive control shape distinct trajectories of adolescent substance use, underscoring adolescence as a critical window for the early identification and implementation of neurodevelopmentally sensitive interventions for substance use disorders.

neuroscience↗

bioRxiv2025

Maturation of striatal dopamine supports the development of habitual behavior through adolescence

Developmental trajectories during the transition from adolescence to adulthood contribute to the establishment of stable, adult forms of operation. Understanding the neural mechanisms underlying this transition is crucial for identifying variability in normal development and the onset of psychiatric disorders, which typically emerge during this time. Habitual behaviors can serve as a model for understanding brain mechanisms underlying the stabilization of adult behavior, while also conferring risk for psychopathologies. Dopaminergic (DA) processes in the basal ganglia are thought to facilitate the formation of habits; however, developmental trajectories of habits and the brain systems supporting them have not been characterized in vivo in developing humans. The current study examined trajectories of habitual behavior from adolescence to adulthood and sought to understand how the maturing striatal DA system may act as a potential mechanism in the process of habit formation. We used data from two longitudinal studies (combined n = 217, 10 - 32 years of age, 1-3 visits each, 320 total sessions) to characterize normative developmental trajectories of basal ganglia tissue iron concentration (a proxy for DA-related neurophysiology) and goal-direct and habitual control behaviors in a two-stage decision-making task. Tissue iron concentrations across the basal ganglia and habitual responding during the two-stage sequential decision-making task both increased with age (all p < 0.001). Importantly, habitual responding was associated with tissue iron concentrations in the putamen (F = 4.34, p = 0.014), such that increases in habitual responding were supported by increases in putamen tissue iron concentration during childhood through late adolescence. Exploratory analyses of further subdivisions of anatomical regions found that this association was specific to the posterior putamen. These results provide novel evidence in humans that habitual behavior continues to mature into adulthood and may be supported by increased specialization of reward systems.

neuroscience↗

bioRxiv2022

Puberty contributes to adolescent development of fronto-striatal functional connectivity supporting inhibitory control

Adolescence is defined by puberty and represents a period characterized by neural circuitry maturation (e.g., fronto-striatal systems) facilitating cognitive improvements. Though studies have characterized age-related changes, the extent to which puberty influences maturation of fronto-striatal networks is less known. Here, we combine two longitudinal datasets to characterize the role of puberty in the development of fronto-striatal resting-state functional connectivity (rsFC) and its relationship to inhibitory control in 106 10-18-year-olds. Beyond age effects, we found that puberty was related to decreases in rsFC between the caudate and the anterior vmPFC, rostral and ventral ACC, and v/dlPFC, as well as with rsFC increases between the dlPFC and nucleus accumbens (NAcc) across males and females. Stronger caudate rsFC with the dlPFC and vlPFC during early puberty was associated with worse inhibitory control and slower correct responses, respectively, whereas by late puberty, stronger vlPFC rsFC with the dorsal striatum was associated with faster correct responses. Taken together, our findings suggest that certain fronto-striatal connections are associated with pubertal maturation beyond age effects, which, in turn are related to inhibitory control. We discuss implications of puberty-related fronto-striatal maturation to further our understanding of pubertal effects related to adolescent cognitive and affective neurodevelopment.

neuroscience↗

bioRxiv2021

Impulsivity and Emotional Dysregulation Predict Choice Behavior During a Competitive Multiplayer Game in Adolescents with Borderline Personality Disorder

Impulsivity and emotional dysregulation are two core features of borderline personality disorder (BPD), and the neural mechanisms recruited during mixed-strategy interactions overlap with frontolimbic networks that have been implicated in BPD. We investigated strategic choice patterns during the classic two-player game, Matching Pennies, where the most efficient strategy is to choose each option randomly from trial-to-trial to avoid exploitation by one's opponent. Twenty-seven female adolescents with BPD (mean age: 16 years) and twenty-seven age-matched female controls (mean age: 16 years) participated in an experiment that explored the relationship between strategic choice behavior and impulsivity in both groups and emotional dysregulation in BPD. Relative to controls, BPD participants showed fewer reinforcement learning biases, increased coefficient of variation in reaction times (CV), and more anticipatory decisions. A subset of BPD participants characterized by high levels of impulsivity and emotional dysregulation showed increased reward rate, increased entropy in choice patterns, decreased CV, and fewer anticipatory decisions relative to participants with lower indices, and emotion dysregulation mediated the relationship between impulsivity and CV in BPD. Finally, exploratory analyses revealed that increased vigilance to outcome was associated with higher reward rates, decreased variability in SRT, and fewer anticipatory decisions. In BPD, higher levels of emotion dysregulation corresponded to increased vigilance to outcome, and mediated its relationship with choice behavior. Together, our results suggest that impulsivity and emotional dysregulation contribute to variability in mixed-strategy decision-making in BPD, the latter of which may influence choice behavior by increasing attention to outcome information during the task.

neuroscience↗

bioRxiv2020

Dopamine-related striatal neurophysiology is associated with specialization of frontostriatal reward circuitry through adolescence

Characterizing developmental changes in frontostriatal circuitry is critical to our understanding of adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and sensation seeking, and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We combine longitudinal MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology with functional magnetic resonance imaging indices of resting-state and reward-state connectivity to investigate the contribution of dopaminergic processes to developmental changes in frontostriatal circuitry. Connectivity between the nucleus accumbens and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood. Nucleus accumbens tissue-iron mediated age-related changes and was associated with variability in connectivity. Our results provide evidence that developmental changes in dopamine-related striatal properties contribute to specialization of frontostriatal circuitry, potentially underlying changes in sensation seeking and reward sensitivity into adulthood.

neuroscience↗