Biology subjects

Vijayakumar, N.

Publications and source records attributed to Vijayakumar, N..

11 recordsLinked to original sources

bioRxiv2026

Global Structural Brain-Age in Adolescence: Application of an Established Method to Short-Interval, Longitudinal Data

Brain-age estimates from grey matter structure provide a promising tool to examine the neurobiology of mental health. However, whether existing models generalise to longitudinal adolescent data remains unclear. The CentileBrain Global-BrainAGE Lifespan Model, was applied to N=138 participants (74 females, 64 males) from the Longitudinal Adolescent Brain Study. Participants completed 2-14 MRI scans between the ages of 12-17 years (752 datapoints). Model fit, prediction accuracy and longitudinal consistency were examined. Results showed moderate-to-good longitudinal consistency and reliability, consistent with high-performing cross-sectional age-to-brain-age correlations in youth cohorts. However, the model systematically overestimated brain-age changes relative to chronological changes, and prediction accuracy was unstable, with the mean absolute error increasing with age. Despite sex-specific brain-age calculations, on average, females showed older brain-ages compared with males. Further, younger adolescents were underpredicted, while older adolescents were overpredicted, indicating that standard model adjustments and assumptions may not be applicable.

neuroscience↗

bioRxiv2025

Oestradiol and Progesterone Variability in Adolescent Females: Associations with Brain Structure and Mental Health Problems

ObjectiveAdolescent females are at increased risk for adverse mental health problems, and puberty is thought to be a critical factor. Pubertal onset involves substantial variability in oestradiol (E2) and progesterone (P4), yet the impact of these hormone dynamics remains unclear. We investigated whether within-individual E2 and P4 variability across one month relates to brain structure and mental health problems in adolescent females. MethodsParticipants were 147 females (11-17 years) from the community-based, cross-sectional Puberty and NeuroDevelopment in Adolescents (PANDA) study in Australia. Salivary E2 and P4 were collected weekly for one month, with variability indexed as within-subject standard deviation. Structural MRI was acquired on the final sampling day. Mental health problems were assessed via self- and parent-report. Linear regression and mediation analyses tested associations between hormone variability, brain structure, and mental health, adjusting for demographics. ResultsGreater P4 variability was associated with smaller left thalamus volume (Cohens d = -0.26, pFDR = 0.031). Higher E2 variability was associated with fewer anxiety (d = -0.170, pFDR = 0.043) and depressive symptoms (d = -0.179, pFDR = 0.036), lower emotion dysregulation (d = -0.179, pFDR = 0.036), and smaller right hippocampus volume in pre-menarchal adolescents (d = -0.192, p = 0.02). Weekly reductions in E2 predicted lower positive affect (d = 0.084, p = 0.048). ConclusionThese findings indicate that hormone variability may meaningfully shape brain and behavioural development in adolescent girls differently from hormone-related transitions in adulthood. Larger, replicable, and longer-term studies are needed to confirm these patterns. Oestradiol and Progesterone Variability in Adolescent Females: Associations with Brain Structure and Mental Health Problems. Muskan Khetan 1, Ye Ella Tian 2, Nandita Vijayakumar 3,4, Sarah Whittle 1,4 O_LICentre for Youth Mental Health, University of Melbourne, Australia C_LIO_LIDepartment of Psychiatry, University of Melbourne, Australia C_LIO_LIMurdoch Childrens Research Institute, Australia C_LIO_LISchool of Psychology, Deakin University, Australia C_LI

neuroscience↗

bioRxiv2025

Linking Oestradiol (E2) Timing and Tempo, Brain Development, and Mental Health in Adolescent Females

Background: Earlier timing and faster tempo of puberty have been associated with altered brain development and increased mental health symptoms in adolescents, particularly females. However, the role of oestradiol (E2) in these associations is unclear. Methods: Using longitudinal data from the US-based Adolescent Brain Cognitive Development Study SM (ABCD Study (R), we investigated whether, in females (N ~ 3k), E2 timing (at age 10) and tempo (rate of change from age 10 to 12) were prospectively associated with mental health symptoms at age 13 via structural brain development from age 10 to 12. Linear mixed-effects models and Bayesian mediation models were fitted to investigate the aims of the study. Results: Findings showed that E2 timing was not associated with mental health symptoms. However, earlier E2 timing was associated with a greater reduction in total cortical volume, total surface area, and surface area in the superior and middle temporal cortex over time. Further, a faster E2 tempo was associated with an increase in mental health symptoms, and this association was mediated by a faster reduction in total cortical volume and total surface area over time. Conclusion: Findings suggest that earlier E2 timing and faster E2 tempo contribute to accelerated development of gray matter structure in adolescent females, and for E2 tempo, such associated brain changes may partly contribute to increased mental health risk.

neuroscience↗

bioRxiv2024

Pubertal hormones and the early adolescent female brain: a multimodality brain MRI study

Puberty is a critical developmental process that is associated with changes in steroid hormone levels, which are believed to influence adolescent behaviour via their effects on the developing brain. So far, there are limited and inconsistent findings regarding the relationship between steroid hormones and brain structure and function in adolescent females, with many existing studies employing small sample sizes. Thus, in this study, we explored the association between oestradiol (E2), testosterone (Tes) and dehydroepiandrosterone (DHEA) and brain structure (gray matter volume, sulcal depth, cortical thickness and white matter microstructure) and function (resting-state connectivity, emotional n-back task-related function) in 3024 adolescent females (age 8.92 - 13.33 years, mean age (SD) = 10.37 (0.94) years) from the Adolescent Brain Cognitive DevelopmentSM (ABCD(R)) Study. We used elastic-net regression with cross- validation to investigate associations between hormones and brain phenotypes derived from multiple imaging modalities. We found that structural brain features, including cortical thickness, sulcal depth, and white matter microstructure, were among the most important features associated with hormones. E2 was most strongly associated with prefrontal and premotor regions involved in working memory and emotion processing, while Tes and DHEA were most strongly associated with parietal and occipital regions involved in visuospatial functioning. All three hormones were also associated with prefrontal, temporoparietal junction and insula cortices. Thus, using an advanced methodological approach, this study suggests both unique and overlapping neural correlates of pubertal hormones in adolescent females and sheds light on the mechanisms by which puberty influences adolescent development and behaviour.

neuroscience↗

bioRxiv2023

Corticolimbic connectivity mediates the relationship between pubertal timing and mental health problems

BackgroundUndergoing puberty ahead of peers ("earlier pubertal timing") is an important risk factor for mental health problems during early adolescence. The current study examined pathways between pubertal timing and mental health via connectivity of neural systems implicated in emotional reactivity and regulation (specifically corticolimbic connections) in 9- to 14-year-olds. MethodResearch questions were examined in the Adolescent Brain Cognitive Development (ABCD) Study, a large population representative sample in the United States. Linear mixed models examined associations between pubertal timing and resting-state corticolimbic connectivity. Significant connections were examined as potential mediators of the relationship between pubertal timing and mental health (withdrawn depressed and rule-breaking delinquency) problems. Exploratory analyses interrogated whether the family environment moderated neural risk patterns in those undergoing puberty earlier than their peers. ResultsEarlier pubertal timing was related to decreased connectivity between limbic structures (bilateral amygdala and right hippocampus) and the cingulo-opercular network (CON), as well as between the left hippocampus and ventral attention network (VAN). Corticolimbic connections also mediated the relationship between earlier pubertal timing and increased withdrawn depressed problems (but not rule-breaking delinquency). Finally, parental acceptance buffered against limbic-CON connectivity patterns that were implicated in withdrawn depressed problems in those undergoing puberty earlier than their peers. ConclusionFindings highlight the role of decreased corticolimbic connectivity in mediating pathways between earlier pubertal timing and withdrawn depressed problems, and we present preliminary evidence that the family environment may buffer against these neural risk patterns during early adolescence.

neuroscience↗

bioRxiv2020

A longitudinal analysis of puberty-related cortical development

The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether individual differences in the rate of pubertal maturation (or "pubertal tempo") was associated with variations in cortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important individual differences in the coupling of these developmental processes.

neuroscience↗

bioRxiv2020

Development of attention networks from childhood to young adulthood: A study of performance, intraindividual variability and cortical thickness

Human cognitive development is manifold, with different functions developing at different speeds at different ages. Attention is an important domain of this cognitive development, and involves distinct developmental trajectories in separate functions, including conflict processing, selection of sensory input and alertness. In children, several studies using the Attention Network Test (ANT) have investigated the development of three attentional networks that carry out the functions of executive control, orienting and alerting. There is, however, a lack of studies on the development of these attentional components across adolescence, limiting our understanding of their protracted development. To fill this knowledge gap, we performed a mixed cross-sectional and longitudinal study using mixed methods to examine the development of the attentional components and their intraindividual variability from late childhood to young adulthood (n = 287, n observations = 408, age range = 8.5-26.7 years, mean follow up interval = 4.4 years). The results indicated that executive control stabilized during late adolescence, while orienting and alerting continued to develop into young adulthood. In addition, a continuous development into young adulthood was observed for the intraindividual variability measures of orienting and alerting. In a subsample with available magnetic resonance imaging (MRI) data (n =169, n observations = 281), higher alerting scores were associated with thicker cortices within a right prefrontal cortical region and greater age-related cortical thinning in left rolandic operculum, while higher orienting scores were associated with greater age-related cortical thinning in frontal and parietal regions. Finally, increased consistency of orienting performance was associated with thinner cortex in prefrontal regions and reduced age-related thinning in frontal regions.

neuroscience↗

bioRxiv2019

Feeling left out or just surprised? Neural correlates of social exclusion and expectancy violations in adolescence

Social belonging and affiliation are important human drives that impact decision-making and health outcomes. While neural responses to social exclusion are increasingly well-characterized, studies rarely identify whether these responses reflect the affective distress or expectancy violation associated with exclusion. The present study compares neural responses to exclusion and over-inclusion, a similarly unexpected social occurrence that violates fair play expectations, but does not involve rejection, with a focus on implications for models of dorsal anterior cingulate cortex (dACC) function. In an fMRI adaptation of the Cyberball paradigm with human adolescents 11.1-17.7 years of age (N=69), we employed parametric modulators to examine scaling of neural signal with cumulative exclusion and inclusion events. The use of parametric modulators overcomes arbitrary definitions of condition onsets and offsets imposed on fluid, continuous gameplay. In support of the notion that the dACC plays a role in processing affective distress, this region exhibited greater signal with cumulative exclusion than cumulative inclusion events. However, this difference was partly driven by diminished signal accompanying cumulative inclusion, a finding that does not conform to either affective distress or expectancy violation model predictions. Additionally, we found that signal in the insula and dorsomedial prefrontal cortex scaled uniquely with social exclusion and over-inclusion, respectively, while conjunction analyses revealed that the rostromedial prefrontal cortex and left intraparietal sulcus responded similarly to both conditions. These findings shed light on which neural regions may exhibit patterns of differential sensitivity to exclusion or over-inclusion, as well as those that are more broadly engaged by both types of social interaction.

neuroscience↗

bioRxiv2019

Affective reactivity during adolescence: Associations with age, puberty and testosterone

Adolescence is a period of heightened social engagement that is accompanied by normative changes in neural reactivity to affective stimuli. It is also a period of concurrent endocrine and physical changes associated with puberty. A growing body of research suggests that hormonal shifts during adolescence impact brain development, but minimal research in humans has examined the relationship between intra-individual changes in puberty and brain function. The current study examines linear and nonlinear changes in affective reactivity in a longitudinal sample of 82 adolescents who underwent three fMRI sessions between the ages of 9 and 18 years. Changes in response to affective facial stimuli were related to age, pubertal stage, and testosterone levels. Using multilevel modelling, we highlight extensive nonlinear development of socio-emotional responsivity across the brain. Results include mid-pubertal peaks in amygdala and hippocampus response to fearful expressions, as well as sex differences in regions subserving social and self-evaluative processes. However, testosterone levels exhibited inverse patterns of association with neural response compared to pubertal stage in females (e.g. U-shaped relationship with the amygdala and hippocampus). Findings highlight potentially unique roles of age, pubertal stage and testosterone on socio-emotional development during adolescence, as well as sex differences in these associations.

neuroscience↗

bioRxiv2017

Development of subcortical volumes across adolescence in males and females: A multisample study of longitudinal changes

The developmental patterns of subcortical brain volumes in males and females observed in previous studies have been inconsistent. To help resolve these discrepancies, we examined developmental trajectories using three independent longitudinal samples of participants in the age-span of 8-22 years (total 216 participants and 467 scans). These datasets, including Pittsburgh (PIT; University of Pittsburgh, USA), NeuroCognitive Development (NCD; University of Oslo, Norway), and Orygen Adolescent Development Study (OADS; The University of Melbourne, Australia), span three countries and were analyzed together and in parallel using mixed-effects modeling with both generalized additive models and general linear models. For all regions and across all samples, males were found to have significantly larger volumes as compared to females, and significant sex differences were seen in age trajectories over time. However, direct comparison of sample trajectories and sex differences identified within samples were not consistent. The trajectories for the amygdala, putamen, and nucleus accumbens were most consistent between the three samples. Our results suggest that even after using similar preprocessing and analytic techniques, additional factors, such as image acquisition or sample composition may contribute to some of the discrepancies in sex specific patterns in subcortical brain changes across adolescence, and highlight region-specific variations in congruency of developmental trajectories.

neuroscience↗

bioRxiv2017

Structural brain development: a review of methodological approaches and best practices

Continued advances in neuroimaging technologies and statistical modelling capabilities have improved our knowledge of structural brain development in children and adolescents. While this has provided an increasingly nuanced understanding of brain development, the field is still plagued by inconsistent findings. This review highlights the methodological diversity in existing longitudinal magnetic resonance imaging (MRI) studies on structural brain development during childhood and adolescence, and addresses how such variation might contribute to inconsistencies in the literature. We discuss the impact of method choices at multiple decision points across the research process, from study design and sample selection, to image processing and statistical analysis. We also highlight the extent to which different methodological considerations have been empirically examined, drawing attention to specific areas that would benefit from future investigation. Where appropriate, we recommend certain best practices that would be beneficial for the field to adopt, including greater completeness and transparency in reporting methods, in order to ultimately develop an accurate and detailed understanding of normative child and adolescent brain development.

scientific communication and education↗