Sex and pubertal stage as moderators of the association between resting-state connectivity of striatal circuitry and reward sensitivity in the Adolescent Brain Cognitive Development study.
Aug 2026· Developmental Cognitive Neuroscience· Vol 81, pp.
101796
· 0 citations· 103 references
Medicine
Abstract
Altered reward sensitivity (either heightened or blunted) has been observed in a range of psychiatric disorders. Understanding neurodevelopmental pathways associated with individual differences in reward sensitivity will therefore help inform prevention and intervention efforts for a range of disorders. In this Registered Report, we used data from the Adolescent Brain Cognitive Development℠ study (ABCD study®), from the baseline, 2-year follow-up, and 4-year follow-up waves of data collection, when participants were on average aged 10, 12, and 14 years old, respectively, to examine these pathways using resting-state functional magnetic resonance imaging. Our aims were to examine whether striatal connectivity with the default mode network and cingulo-opercular network were associated with individual differences in reward sensitivity, and whether effects differed by sex and pubertal stage. Results indicated that reward sensitivity was positively associated with ventral striatum connectivity with the default mode network and negatively associated with ventral striatum connectivity with the cingulo-opercular network. In addition, adolescents with higher connectivity between the dorsal striatum (the caudate and putamen) and the cingulo-opercular network exhibited greater declines in reward sensitivity with pubertal development. Overall, increased striatal connectivity with the cingulo-opercular network may be associated with decreased reward sensitivity due to heightened regulation of reward-related function by the cingulo-opercular network, which plays a role in self-regulation and cognitive control.
Pubertal maturation drives brain development, yet longitudinal evidence linking it to resting-state functional connectivity (rs-FC) in early adolescence remains limited, and adolescent mental-health trajectories differ by sex, motivating sex-specific analyses. In a general-population cohort (255 adolescents scanned at Time 1; 68 girls and 70 boys with analysable two-wave data), we examined longitudinal change in rs-FC between ages ~11.5 and ~13.6 years, separately by sex. Whole-brain analyses were applied without predefined regions of interest, using principal component analysis (PCA) as a data-driven screen and network-based statistics (NBS) to localize subnetworks associated with pubertal stage (Tanner stage). Among girls, Tanner breast stage at Time 2 was significantly associated with the fingerprint stability (within-individual similarity) of whole-brain rs-FC. NBS identified a subnetwork positively associated with Tanner breast stage, linking the thalamus to visual, auditory, and motor areas and the prefrontal operculum to frontoparietal association areas, with the PCA screen converging on thalamic involvement. No comparable associations were observed in boys. These findings suggest that the level of pubertal maturation is associated with the longitudinal stability of large-scale brain networks in girls.
Susumu Morita, K. Kasai, Masahiro Kiyota et al.· Neurosciences research· 0 citations
BACKGROUND
Variation in pubertal maturation relative to same-age, same-sex peers (pubertal timing) has been linked to increased risk for depressive symptoms during adolescence. This developmental period is also characterized by substantial reorganization of functional brain networks. However, how pubertal timing relates to resting-state functional connectivity (rsFC) changes and depression risk remains unclear.
METHODS
We examined pubertal timing and rsFC associations in 9-11-year-old preadolescents from the Adolescent Brain Cognitive Development (ABCD) Study. Pubertal timing was estimated using a puberty age gap approach based on parent-reported physical development. Linear mixed-effects and Bayesian multilevel models were used to assess cross-sectional and longitudinal associations between pubertal timing and rsFC across large-scale functional brain networks. We also tested whether rsFC differences explained associations between pubertal timing and later depressive symptoms.
RESULTS
Earlier pubertal timing was associated with heterogeneous rsFC patterns, with stronger and more widespread effects in females. Earlier pubertal timing was associated with rsFC increases and decreases across sensory-motor and association networks in females, whereas in males, associations were more limited and localized to sensorimotor and cerebellar systems. Longitudinally, earlier pubertal timing in females predicted reductions in rsFC at the 2-year follow-up, with no significant associations in males. rsFC differences did not explain the pubertal timing and later depressive symptoms association.
CONCLUSIONS
Pubertal timing is associated with sex-specific patterns of brain functional connectivity during early adolescence, with greater heterogeneity and broader network involvement in females. These findings suggest that pubertal maturation contributes to early reorganization of functional brain networks, although these changes did not explain subsequent depressive symptoms.
Athanasia Metoki, B. Kay, R. Chauvin et al.· Biological Psychiatry: Cogni...· 0 citations
A sex-specific pattern within the dopaminergic pathways may underlie the clinical divergences between male and female patients with Parkinson’s disease (PD) over the disease course. One hundred forty-seven drug-naive PD patients and 38 controls were enrolled. Anatomical and rs-fMRI images were acquired at baseline. Clinical assessments were performed at baseline and (yearly) at follow-ups for 4 years. Using connectivity-based parcellation, we obtained three ROIs for the sensorimotor, limbic, and cognitive striatal functional subregions, which were used as seeds for functional connectivity (FC) analyses. Baseline and longitudinal clinical data at 4 years were correlated with baseline imaging findings. Female PD showed reduced sensorimotor FC with the superior frontal gyrus compared with male PD patients, while no significant sex-related effects emerged for limbic or cognitive striatal seeds. Compared with controls, PD males and females showed both increased and decreased FC involving the three striatal subregions and frontal, insula, hippocampus, and cingulate areas, while voxel-based morphometry revealed no significant sex-related structural differences. Baseline FC changes in limbic and cognitive striatal circuits were associated with slower motor and cognitive progression over 4 years. Although not supported by formal interaction effects, this pattern may underlie sex-specific vulnerability, possibly reflecting different plasticity responses shaped by biological sex.
R. de Micco, S. Satolli, Noemi Piramide et al.· npj Parkinson's Disease· 0 citations
Importance: Adolescent cannabis use is a growing concern due to its associations with long-term adverse mental health outcomes. However, the distinct, temporal associations of neurodevelopmental factors and childhood adverse life experiences (ALEs) with adolescent substance use in have not yet been fully elucidated. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to prospectively examine neurobiological and socioenvironmental predictors of cannabis onset. Objective: To investigate magnetic resonance imaging-derived neurodevelopmental cortical brain Age Gap Estimate (brainAGE) and adverse life events as risk factors of early cannabis initiation. Design, Setting, and Participants: The ABCD Study is a longitudinal study across 22 sites in the United States. Data are collected starting at approximately 10 years old (currently at year-7 follow-up). Our analyses comprised 6688 (48% female) youth after exclusions. Main Outcomes and Measures: Cox proportional hazard models were computed to investigate brainAGE-sex interactions and 10 adversity dimensions at baseline as predictors of time to cannabis initiation up to age 18. Results: Mean age of initiation was 14.8 years (SD=1.43). Global brainAGE was modestly associated with cannabis initiation in females only (Hazard Ratio [HR]=1.05; 95% Confidence Interval [CI]=1.00-1.10, p = .049). Low socioeconomic status, caregiver substance use, family anger and arguments, and caregiver lack of supervision were associated with initiation (HRs = 1.11, 1.56, 1.09, 0.85, respectively; CIs = 1.04-1.19, 1.44-1.69, 1.09-1.19, 0.76-0.91, respectively; p's < .05). Other ALE dimensions and network-specific brainAGEs were not significantly associated with initiation. Conclusions and Relevance: Findings suggest that while cortical brainAGE may be somewhat increase vulnerability to adolescent cannabis use in females, its contributions are modest at best. In contrast, early childhood adversities such as socioeconomic factors and familial characteristics may present more substantive targets for prevention and intervention.
K. Thiessen, Y. Yu, L. Schmid et al.· medRxiv· 0 citations
Associations between patterns of brain connectivity and brain structural features have transdiagnostic relevance to psychopathology. There is considerable evidence for disruptions to the hippocampus and temporoparietal brain systems in psychotic disorders. The present study examines structure–function relationships—specifically, the relation of hippocampal volume with patterns of temporoparietal effective connectivity—in youth at clinical high-risk for psychosis (CHR-P) and healthy controls (HCs). Participants at CHR-P and HCs completed clinical symptom measures and magnetic resonance imaging at baseline (n = 388, 42.5% female, age = 19.8 ± 4.2) in the second cohort of the North American Prodrome Longitudinal Study. Group Iterative Multiple Model Estimation established a common functional network of temporoparietal effective connectivity in the full sample. Next, supervised (assuming the CHR-P and HC groups represent classes) and unsupervised (data-driven) clustering procedures interrogated effective connectivity parameters relevant to subsamples. Mean difference tests by unsupervised cluster membership determined whether clusters formed based on temporoparietal effective connectivity differed in hippocampal volume. Clusters were also compared on representation of CHR-P and positive and negative symptom totals to determine whether unsupervised clustering recovered clinical features. Unsupervised clustering generated two clusters that differed significantly in right hippocampal volume and attenuated positive and negative symptoms with small-to-medium effect sizes. The cluster demonstrating reduced right hippocampal volume reported greater symptoms. Unsupervised clustering did not recover diagnostic groups. Findings are consistent with literature indicating the transdiagnostic relevance of hippocampal volume to organizational properties of brain functional networks and patterns of temporoparietal connectivity.
K. Aberizk, B. Ku, Hengyi Cao et al.· Brain Structure and Function· 0 citations
First episodes of affective disorders often emerge during adolescence and young adulthood. Alterations in resting-state functional connectivity (RSFC) have been reported in affective disorders, yet findings are heterogeneous and associations of RSFC with subclinical affective symptoms in community samples remain limited. A better understanding of these underlying neurobiological mechanisms may aid in identifying early vulnerability markers of affective disorders. We examined associations between affective symptom severity and both static and dynamic RSFC using resting-state fMRI data from 512 adolescents and young adults (aged 14–23) drawn from an age- and sex-stratified population-based sample. Group independent component analysis was used to derive RSFC measures. Associations with depressive and manic symptom severity were assessed while controlling for age and sex. Dynamic RSFC was analyzed using a sliding-window approach. Static RSFC showed significant effects of age and sex but no associations with affective symptoms. Dynamic RSFC analysis identified four connectivity states. In one state, manic symptom severity and its interaction with depressive symptom severity were associated with connectivity between the postcentral gyrus and the right superior temporal gyrus. Additionally, the dynamic index fraction of time showed interactions of affective symptoms with age and sex. Overall, RSFC measures demonstrated limited sensitivity to subclinical affective symptom variation in community youth, with only a single state-specific association observed. These findings suggest that subtle alterations in somatomotor-default mode network connectivity may reflect early vulnerability-related processes, though replications and further research are required. Key limitations include the use of very brief symptom measures and developmental heterogeneity across the sample.
Paula M. Henneberg, Katja Beesdo-Baum, M. Marxen et al.· Translational Psychiatry· 0 citations
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