Biology subjects

Foran, W.

Publications and source records attributed to Foran, W..

At least 19 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

Developmental Changes in Gray Matter Microstructure and Local Brain Connectivity Support Inhibitory Control from Adolescence to Young Adulthood

Background: Adolescence is marked by improvements in inhibitory control along with brain maturational processes affecting function and structure of cortical circuitry. Preliminary evidence shows a developmental decrease of local neuronal inputs, suggesting a weakening of local connectivity supporting circuit refinement and mature behavior. Microstructural changes in gray matter, arising from processes such as synaptic pruning and myelination, may support this refinement, though it remains unknown how microstructural features interact with the reconfiguration of functional circuitry, or how this unfolds in vivo in normative development to support mature cognitive functioning. Methods: In this study, 175 participants ages 10-26 (93F; 17.32{+/-}4.82yo) completed an anti-saccade task, a developmentally-validated measure of inhibitory control, as well as a 3T MRI scan involving a multi-shell diffusion weighted imaging acquisition, multi-echo resting state fMRI, and structural (T1w, T2w) scans. We computed measures of neurite density (NDI) in gray matter using neurite orientation dispersion and density imaging, local functional connectivity with surface-based and volumetric regional homogeneity (ReHo), and intracortical myelin using T1w/T2w ratio. Generalized additive models examined non-linear age-related trends across a number of cortical and subcortical regions implicated in inhibitory control, as well as associations with anti-saccade performance. Results: We found that NDI significantly increased with age in all regions while ReHo decreased. Greater NDI was associated with more accurate anti-saccade performance and lower ReHo, which remained after residualizing NDI for T1w/T2w ratio, suggesting that microstructural reorganization beyond myelination may underlie functional specialization throughout adolescence. Lower ReHo, specifically in young adolescents, also resulted in better anti-saccade performance. Finally, an interaction between ReHo and NDI, rather than either measure alone, best predicted inhibitory control performance, such that the maturity of neurite density had the greatest effect when local connectivity was high, suggesting immaturity. Conclusions: Our results suggest that the joint maturation of microstructural elements and associated specialization of local functional circuitry interact to support the emergence of stable adult-level inhibitory control.

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

Heterochronous laminar maturation in the human prefrontal cortex

The human prefrontal cortex (PFC) exhibits markedly protracted developmental plasticity, yet whether reductions in plasticity occur synchronously across prefrontal cortical layers is unclear. Animal studies have shown that intracortical myelin consolidates developing circuits by restricting ongoing neuronal plasticity. Here, we use longitudinal myelin-sensitive imaging collected at ultra-high field to investigate whether superficial and deep PFC layers exhibit different timeframes of malleability. We find that myelin matures earlier in deep than in superficial compartments of the cortical ribbon; this laminar divergence in maturational timing is differentially expressed across cytoarchitecturally and functionally distinct frontal regions. By integrating myelin mapping with EEG and behavioral phenotyping, we provide evidence that prefrontal myelin impacts timescales of neural activity, task learning rates, and cognitive processing speed. Heterochronous myelination across deep and superficial layers is an underrecognized mechanism through which human association cortex balances cognitively-relevant increases in circuit stability and efficiency with extended neuroplasticity.

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↗

bioRxiv2024

Prefrontal Excitation/ Inhibition Balance Supports Adolescent Enhancements in Circuit Signal to Noise Ratio

The development and refinement of neuronal circuitry allow for stabilized and efficient neural recruitment, supporting adult-like behavioral performance. During adolescence, the maturation of PFC is proposed to be a critical period (CP) for executive function, driven by a break in balance between glutamatergic excitation and GABAergic inhibition (E/I) neurotransmission. During CPs, cortical circuitry fine-tunes to improve information processing and reliable responses to stimuli, shifting from spontaneous to evoked activity, enhancing the SNR, and promoting neural synchronization. Harnessing 7T MR spectroscopy and EEG in a longitudinal cohort (N = 164, ages 10-32 years, 283 neuroimaging sessions), we outline associations between age-related changes in glutamate and GABA neurotransmitters and EEG measures of cortical SNR. We find developmental decreases in spontaneous activity and increases in cortical SNR during our auditory steady state task using 40 Hz stimuli. Decreases in spontaneous activity were associated with glutamate levels in DLPFC, while increases in cortical SNR were associated with more balanced Glu and GABA levels. These changes were associated with improvements in working memory performance. This study provides evidence of CP plasticity in the human PFC during adolescence, leading to stabilized circuitry that allows for the optimal recruitment and integration of multisensory input, resulting in improved executive function.

neuroscience↗

bioRxiv2023

Aperiodic EEG and 7T MRSI evidence for maturation of E/I balance supporting the development of working memory through adolescence

Postmortem animal and human models suggest changes through adolescence in aspects of excitatory glutamatergic and inhibitory GABAergic function (E/I) in prefrontal cortex (PFC) suggestive of critical period plasticity at a time of significant cognitive development. Recently, using high field 7T Magnetic Resonance Spectroscopic Imaging (MRSI), we found in vivo evidence for increases in PFC glutamate/GABA balance through adolescence into adulthood. We now extend these MRSI findings by investigating, in the same 164 10- 32-year-old participants, its correspondence with EEG aperiodic activity, an independent measure of E/I balance elucidating changes in neural activity. Results showed decreases in PFC aperiodic activity from adolescence to adulthood, that were associated with MRSI measures of glutamate/GABA balance as well as mediating the association between age and EEG aperiodic activity. Further, changes in aperiodic activity predicted performance on a working memory task, indicating a role for E/I based changes in PFC signaling mechanisms in supporting maturation of cognitive control. Taken together, these results suggest that PFC is undergoing critical period plasticity through adolescence evident in both neurotransmitter and neural function that supports cognitive development.

neuroscience↗

bioRxiv2023

Multivariate and Regional Age-Related Change in Basal Ganglia Iron in Neonates

In the perinatal period, reward and cognitive systems begin trajectories, influencing later psychiatric risk. The basal ganglia is important for reward and cognitive processing but early development has not been fully characterized. To assess age-related development, we used a measure of basal ganglia physiology, specifically brain tissue iron, obtained from nT2* signal in rsfMRI, associated with dopaminergic processing. We used data from the Developing Human Connectome Project (N=464) to assess how moving from the prenatal to the postnatal environment affects rsfMRI nT2*, modeling gestational and postnatal age separately for basal ganglia subregions in linear models. We did not find associations with tissue iron and gestational age [Range: 24.29-42.29] but found positive associations with postnatal age [Range:0-17.14] in the pallidum and putamen, but not the caudate. We tested if there was an interaction between preterm birth and postnatal age, finding early preterm infants (GA<35 weeks) had higher iron levels and changed less over time. To assess multivariate change, we used support vector regression to predict age from voxel-wise-nT2* maps. We could predict postnatal but not gestational age when maps were residualized for the other age term. This provides evidence subregions differentially change with postnatal experience and preterm birth may disrupt trajectories.

neuroscience↗

bioRxiv2023

Gestational and postnatal age associations for striatal tissue iron deposition in early infancy

Striatal development is crucial for later motor, cognitive, and reward behavior, but age-related change in striatal physiology during the neonatal period remains understudied. An MRI-based measure of tissue iron deposition, T2*, is a non-invasive way to probe striatal physiology neonatally, linked to dopaminergic processing and cognition in children and adults. Striatal subregions have distinct functions that may come online at different time periods in early life. To identify if there are critical periods before or after birth, we measured if striatal iron accrued with gestational age at birth [range=34.57-41.85 weeks] or postnatal age at scan [range=5-64 days], using MRI to probe the T2* signal in N=83 neonates in three striatal subregions. We found iron increased with postnatal age in the pallidum and putamen but not the caudate. No significant relationship between iron and gestational age was observed. Using a subset of infants scanned at preschool age (N=26), we show distributions of iron shift between timepoints. In infants, the pallidum had the least iron of the three regions but had the most by preschool age. Together, this provides evidence of distinct change for striatal subregions, a possible differentiation between motor and cognitive systems, identifying a mechanism that may impact future trajectories. HighlightsO_LINeonatal striatal tissue iron can be measured using the T2* signal from rsfMRI C_LIO_LInT2* changed with postnatal age in the pallidum and putamen but not in the caudate C_LIO_LInT2* did not change with gestational age in any of the three regions C_LIO_LIPatterns of iron deposition (nT2*) among regions shift from infancy to preschool C_LI

neuroscience↗

bioRxiv2022

Changes in gamma bursts supporting working memory development through adolescence derived from EEG spectral processing

Adolescence is a stage of development characterized by neurodevelopmental specialization of cognitive processes. In particular, working memory continues to improve through adolescence, with increases in response accuracy and decreases in response latency continuing well into the twenties. Human electroencephalogram (EEG) studies indicate that gamma oscillations (35-65 Hz) during the working memory delay period support the maintenance of mnemonic information guiding subsequent goal-driven behavior, which decrease in power with development. Importantly, recent electrophysiological studies have shown that gamma events, more so than sustained activity, may underlie working memory maintenance during the delay period. However, developmental differences in gamma events during working memory have not been studied. Here, we used EEG in conjunction with a novel spectral event processing approach to investigate age-related differences in transient gamma band activity during a memory guided saccade (MGS) task in 164 10- to 30-year-olds. Total gamma power was found to significantly decrease through adolescence, replicating prior findings. Results from the spectral event pipeline showed age-related decreases in the mean power of gamma events and trial-by-trial power variability across both the delay period and fixation epochs of the MGS task. In addition, we found that while event number decreased with age during the fixation period, it did not appear to change during the delay period resulting in an increasing difference between the number of events during fixation and delay period with development, suggesting that as working memory develops there is greater specificity for gamma events supporting working memory. While average power of the transient gamma events was found to mediate age-related changes in total gamma power, the number of gamma events was unrelated to total power, suggesting that the power of gamma events may underlie the sustained gamma activity seen in EEG literature while the number of events may directly support age-related improvements in working memory maintenance. Our findings provide compelling new evidence for mechanistic changes in neural processing characterized by refinements in neural function as behavior becomes optimized in adulthood.

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↗

bioRxiv2022

Pubertal Development Underlies Optimization of Inhibitory Control Through Specialization of Ventrolateral Prefrontal Cortex

Inhibitory control improves into young adulthood after specialization of relevant brain systems during adolescence. However, the biological mechanisms supporting this unique transition are not well understood. Given that adolescence is defined by pubertal maturation, we examined relative contributions of chronological age and pubertal maturation to inhibitory control development. 105 8-19-year-olds completed 1-5 longitudinal visits (227 visits total) in which pubertal development was assessed via self-reported Tanner stage and inhibitory control was assessed with an in-scanner antisaccade task. As expected, percent and latency of correct antisaccade responses improved with age and pubertal stage. When controlling for pubertal stage, chronological age was distinctly associated with correct response rate. In contrast, pubertal stage was uniquely associated with antisaccade latency even when controlling for age. Chronological age was associated with fMRI task activation in several regions including the right dorsolateral prefrontal cortex, while puberty was associated with right ventrolateral prefrontal cortex (VLPFC) activation. Furthermore, task-related connectivity between VLPFC and cingulate was associated with both pubertal stage and response latency. These results suggest that while age-related developmental processes may support maturation of brain systems underlying the ability to inhibit a response, puberty may play a larger role in the effectiveness of generating cognitive control responses.

neuroscience↗

bioRxiv2022

Changes in prefrontal GABA and glutamate through adolescence supports excitation/inhibition balance

Animal and human postmortem studies provide evidence for changes in gamma-aminobutyric acid (GABA) and glutamate in prefrontal cortex (PFC) during adolescence, suggesting shifts in excitation and inhibition balance consistent with critical period plasticity. However, how GABA and glutamate change through adolescence and how the balance of these inhibitory and excitatory neurotransmitters changes is not well understood in vivo in humans. High field (7 Tesla) Magnetic Resonance Spectroscopic Imaging was used to investigate age-related changes in the balance of GABA/creatine (Cr) and glutamate/Cr in multiple developmentally-relevant regions of PFC in 144 10 to 30-year-olds. Results indicated a homogenous pattern of age-related Glu/Cr decreases across PFC regions, while age-related changes in GABA/Cr were heterogenous, with a mix of stable and decreasing age effects. Importantly, balance between glutamate/Cr and GABA/Cr in areas of prefrontal cortex increased through adolescence, suggesting the presence of critical period plasticity in PFC at this significant time of development when adult trajectories are established.

neuroscience↗

bioRxiv2020

QSIPrep: An integrative platform for preprocessing and reconstructing diffusion MRI

Diffusion-weighted magnetic resonance imaging (dMRI) has become the primary method for non-invasively studying the organization of white matter in the human brain. While many dMRI acquisition sequences have been developed, they all sample q-space in order to characterize water diffusion. Numerous software platforms have been developed for processing dMRI data, but most work on only a subset of sampling schemes or implement only parts of the processing workflow. Reproducible research and comparisons across dMRI methods are hindered by incompatible software, diverse file formats, and inconsistent naming conventions. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing upon a diverse set of software suites to capitalize upon their complementary strengths, QSIPrep automatically applies best practices for dMRI preprocessing, including denoising, distortion correction, head motion correction, coregistration, and spatial normalization. Throughout, QSIPrep provides both visual and quantitative measures of data quality as well as "glass-box" methods reporting. Taken together, these features facilitate easy implementation of best practices for processing of diffusion images while simultaneously ensuring reproducibility.

bioinformatics↗

bioRxiv2020

Towards Reproducible Brain-Wide Association Studies

Magnetic resonance imaging (MRI) continues to drive many important neuroscientific advances. However, progress in uncovering reproducible associations between individual differences in brain structure/function and behavioral phenotypes (e.g., cognition, mental health) may have been undermined by typical neuroimaging sample sizes (median N=25)1,2. Leveraging the Adolescent Brain Cognitive Development (ABCD) Study3 (N=11,878), we estimated the effect sizes and reproducibility of these brain-wide associations studies (BWAS) as a function of sample size. The very largest, replicable brain-wide associations for univariate and multivariate methods were r=0.14 and r=0.34, respectively. In smaller samples, typical for brain-wide association studies (BWAS), irreproducible, inflated effect sizes were ubiquitous, no matter the method (univariate, multivariate). Until sample sizes started to approach consortium-levels, BWAS were underpowered and statistical errors assured. Multiple factors contribute to replication failures4-6; here, we show that the pairing of small brain-behavioral phenotype effect sizes with sampling variability is a key element in wide-spread BWAS replication failure. Brain-behavioral phenotype associations stabilize and become more reproducible with sample sizes of N{gap}2,000. While investigator-initiated brain-behavior research continues to generate hypotheses and propel innovation, large consortia are needed to usher in a new era of reproducible human brain-wide association studies.

neuroscience↗