Biology subjects

Calabro, F.

Publications and source records attributed to Calabro, F..

13 recordsLinked to original sources

bioRxiv2026

Trajectories of Response Inhibition Development in Adolescence

Adolescence is a pivotal developmental period during which cognitive control and the ability to suppress maladaptive impulses undergo profound refinement. Despite extensive behavioral and imaging studies in humans, the neural circuit mechanisms that drive the maturation of inhibitory control remain poorly understood. To address this gap, we performed a longitudinal multimodal study in macaque monkeys spanning the transition from puberty to adulthood, combining behavioral measurements, prefrontal neurophysiology, and structural neuroimaging within the same individuals. Behavioral performance in multiple variants of the antisaccade task improved dramatically across adolescence. In parallel, prefrontal cortical neurons exhibited robust developmental increases in task-related firing, particularly around the generation of goal-directed saccades, indicating maturation of neural representations supporting inhibitory control. Strikingly, trajectories of behavioral improvement and neural activity maturation were tightly predicted by the development of long-range white matter pathways linking frontal cortex with distributed brain networks. These findings identify white matter development as a key systems-level mechanism underlying the emergence of mature inhibitory control and prefrontal neural dynamics and establish a primate framework for understanding developmental vulnerabilities associated with neuropsychiatric disorders that emerge in adolescence and early adulthood.

neuroscience↗

bioRxiv2026

Brain criticality emerges with developmental shifts in frequency-specific excitation-inhibition balance

Adolescent brain maturation involves structural changes effecting a shift in excitation/inhibition (E/I) balance, yet the functional implications of these changes remain unclear. One implication is a shift with respect to criticality. Adult brains, at rest, operate near a critical phase transition - at the boundary between an active, excitation-dominant phase, and an absorbing, inhibition-dominant phase. Special properties emerge when neural systems are balanced at criticality, including maximal susceptibility to perturbation, dynamic range, and information transmission. Thus, a clear picture of how adolescent brain maturation affects E/I balance and criticality is needed to understand how maturational processes shape cognition. Here, we leverage the dynamical properties of longitudinally-collected resting-state EEG recordings during N = 310 sessions from 169 healthy human participants ranging in age from 10 to 33 years old to quantify E/I and proximity to criticality. We find that adult brains operate closer to criticality, including spectrally-widespread increases in long-range temporal correlations and amplitude bistability. We also find band-specific changes in excitation versus inhibition whereby the mechanisms driving low-frequency ({theta} to ) oscillations shift towards lower E/I-possibly because of increasing inhibition-while the mechanisms driving high-frequency ({gamma}) oscillations shift towards higher E/I, possibly because of decreasing inhibition. Opening eyes shifts brains towards lower E/I, and these state-dependent shifts are larger in adults. We simulate developmental effects with a neural mass model of coupled excitatory and inhibitory neurons providing a parsimonious account of how changes in brain dynamics could arise as a function of changes in local connectivity of excitatory and inhibitory neurons. Results indicate developmental movement towards criticality, and greater adaptability to state-specific demands, through adolescence to adulthood, reflecting changes in E/I balance with implications for cognitive development.

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bioRxiv2025

Basal Ganglia Dopamine Availability and Immune Activation Interact and Relate to Anhedonia Severity among Youth with Depression

Anhedonia emerges in adolescence, has putative substrates in neural reward and dopamine systems, and is a hallmark of poor course in depression. Psychoneuroimmunology models suggest altered immune and reward systems may jointly underlie its development. When dopamine availability (rather than function) is considered, immune activation may be understood as a moderator amplifying how lower dopamine levels translate into motivational deficits. This cross-sectional study analyzed data from 55 youth with current depression (Mage=21.4 years; Female=75%). Plasma was assayed for relative quantification of 92 immune proteins, followed by dimensionality reduction via principal component (PC) analysis, forming five PC scores. Dopamine availability was indexed by basal ganglia tissue iron, quantified by MRI R2, a measure detectable in youth. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS), thought to capture overall anhedonia, and Positive Valence Systems Scale (PVSS), which provides overall, anticipatory, and consummatory anhedonia scores. PC1 scores--whose loadings indicated broadly distributed immune protein elevations consistent with general immune activation--moderated the relationship between basal ganglia dopamine availability and anhedonia: At higher PC1 levels, lower dopamine availability was linked to greater overall anhedonia (as measured by SHAPS) and anticipatory anhedonia, but not to consummatory anhedonia. Lower PC2 scores were associated with greater PVSS overall and consummatory anhedonia. Analyses examining individual basal ganglia regions suggest potential differences in dopaminergic-immune interactions across these regions, with effects most consistently observed in the putamen. Findings highlight nuanced neuroimmune pathways underlying anhedonia components in youth and support inflammation-based models of depression emphasizing dopaminergic-immune interplay.

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↗

bioRxiv2024

Brain structure and activity predicting cognitive maturation in adolescence

Cognitive abilities of primates, including humans, continue to improve through adolescence 1,2. While a range of changes in brain structure and connectivity have been documented 3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans 5 did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.

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.

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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

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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

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.

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bioRxiv2021

Adolescent Brain Cognitive Development (ABCD) Community MRI Collection and Utilities

The Adolescent Brain Cognitive Development Study (ABCD), a 10 year longitudinal neuroimaging study of the largest population based and demographically distributed cohort of 9-10 year olds (N=11,877), was designed to overcome reproducibility limitations of prior child mental health studies. Besides the fantastic wealth of research opportunities, the extremely large size of the ABCD data set also creates enormous data storage, processing, and analysis challenges for researchers. To ensure data privacy and safety, researchers are not currently able to share neuroimaging data derivatives through the central repository at the National Data Archive (NDA). However, sharing derived data amongst researchers laterally can powerfully accelerate scientific progress, to ensure the maximum public benefit is derived from the ABCD study. To simultaneously promote collaboration and data safety, we developed the ABCD-BIDS Community Collection (ABCC), which includes both curated processed data and software utilities for further analyses. The ABCC also enables researchers to upload their own custom-processed versions of ABCD data and derivatives for sharing with the research community. This NeuroResource is meant to serve as the companion guide for the ABCC. In section we describe the ABCC. Section II highlights ABCC utilities that help researchers access, share, and analyze ABCD data, while section III provides two exemplar reproducibility analyses using ABCC utilities. We hope that adoption of the ABCCs data-safe, open-science framework will boost access and reproducibility, thus facilitating progress in child and adolescent mental health research.

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bioRxiv2019

Cognitive and default mode networks support developmental stability in functional connectome fingerprinting through adolescence

Pioneering studies have shown that individual correlation measures from resting-state functional magnetic resonance imaging studies can identify another scan from that same individual. This method is known as "connectotyping" or functional connectome "fingerprinting". We analyzed a unique dataset of 12-30 years old (N=140) individuals who had two distinct resting state scans on the same day and again 12-18 months later to assess the sensitivity and specificity of fingerprinting accuracy across different time scales (same day, ~1.5 years apart) and developmental periods (youths, adults). Sensitivity and specificity to identify ones own scan was high (average AUC=0.94), although it was significantly higher in the same day (average AUC=0.97) than 1.5-year years later (average AUC=0.91). Accuracy in youths (average AUC=0.93) was not significantly different from adults (average AUC=0.96). Multiple statistical methods revealed select connections from the Frontoparietal, Default, and Dorsal Attention networks that enhanced the ability to identify an individual. Identification of these features generalized across datasets and improved fingerprinting accuracy in a longitudinal replication data set (N=208). These results provide a framework for understanding the sensitivity and specificity of fingerprinting accuracy in adolescents and adults at multiple time scales. Importantly, distinct features of ones "fingerprint" contribute to ones uniqueness, suggesting that cognitive and default networks play a primary role in the individualization of ones connectome.

neuroscience↗

bioRxiv2019

Neurocognitive development of inhibitory control and substance use vulnerability

Previous research indicates that risk for substance use is associated with poor inhibitory control. However, it remains unclear whether at risk youth use follow divergent patterns of inhibitory control development. As part of the longitudinal National Consortium on Adolescent Neurodevelopment and Alcohol (NCANDA) study, participants (N = 113, baseline age: 12-21) completed a rewarded antisaccade task during fMRI, with up to three time points. We examined whether substance use risk factors, including dimensional measures of psychopathology (externalizing, internalizing) and family history of substance use disorder, were associated with developmental differences in inhibitory control performance and BOLD activation at both the trial-level and within individual antisaccade epochs (cue, preparation, and response). Among substance use risk factors, only externalizing psychopathology predicted developmental differences in inhibitory control, where high externalizing predicted lower correct response rates and faster latencies were observed in early adolescence, but normalized by late adolescence. Neuroimaging results revealed high externalizing was associated with developmentally-stable hypo-activation in the left middle frontal gyrus (trial-level), but divergent developmental patterns of posterior parietal cortex activation (cue epoch). Developmental differences in inhibitory control associated with externalizing suggest early adolescence may be a unique period of substance use vulnerability via cognitive and phenotypic disinhibition.\n\nHighlightsO_LICharacterized inhibitory control development in adolescents at-risk for substance use.\nC_LIO_LIExternalizing psychopathology is associated with lower antisaccade correct response rate and faster latencies in early adolescence.\nC_LIO_LIExternalizing performance differences normalize by late adolescence.\nC_LIO_LIExternalizing is associated with prefrontal hypo-activation across development.\nC_LIO_LIExternalizing moderates age-related increases in posterior parietal cortex activity.\nC_LI

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