The impact of puberty on adolescent brain development

Research has demonstrated that the human brain undergoes significant change in both structure and function during adolescence, but little is known about the role of puberty in this developmental process. The aim of this thesis is to investigate the relationship between puberty and brain development during adolescence. The first two chapters of this thesis summarise the current understanding of the behavioural and brain changes associated with both adolescence and puberty, and review the methods employed to assess puberty in research. Chapters 3 and 4 focus on the relationship between puberty and changes in brain structure. In Chapter 3, the influence of puberty on subcortical structural development is investigated in a large longitudinal MRI dataset, using a mixed effects modelling analysis method. Chapter 4 investigates the relationship between pubertal status, as measured by physical pubertal stage and levels of salivary sex steroid hormones, and white matter structural development in a cross-sectional sample of 12-16 year old boys, using diffusion tensor imaging. In Chapters 5-7, functional brain changes with puberty are explored. Chapters 5 and 6 focus on social emotion processing, where social emotions (e.g. embarrassment) are defined as emotions that require an awareness of other people’s mental states, while basic emotions (e.g. fear) are those which do not. In Chapter 5, the neural correlates of social and basic emotion processing are investigated in relation to pubertal status. In Chapter 6, the fMRI data are reanalysed using psycho-physiological interaction (PPI) analysis to investigate puberty-related changes in functional connectivity during the same task. Chapter 7 explores, in males, how developmental changes in brain function when performing a risk-taking task are related to puberty, independently of chronological age. Finally, in Chapter 8, the results of the empirical studies are summarised and the findings and implications of the thesis are discussed

Development of white matter microstructure and executive functions during childhood and adolescence: a review of diffusion MRI studies

Diffusion magnetic resonance imaging (dMRI) provides indirect measures of white matter microstructure that can be used to make inferences about structural connectivity within the brain. Over the last decade, a growing literature of cross-sectional and longitudinal studies have documented relationships between dMRI indices and cognitive development. In this review, we provide a brief overview of dMRI methods and how they can be used to study white matter and connectivity and review the extant literature examining the links between dMRI indices and executive functions during development. We explore the links between white matter microstructure and specific executive functions: inhibition, working memory and cognitive shifting, as well as performance on complex executive function tasks. Concordance in findings across studies are highlighted, and potential explanations for discrepancies between results, together with challenges with using dMRI in child and adolescent populations, are discussed. Finally, we explore future directions that are necessary to better understand the links between child and adolescent development of structural connectivity of the brain and executive functions

Puberty and risky decision-making in male adolescents

Pubertal development is a potential trigger for increases in risk-taking behaviours during adolescence. Here, we sought to investigate the relationship between puberty and neural activation during risky decision-making in males using functional magnetic resonance imaging (fMRI). Forty-seven males aged 12.5-14.5 years completed an fMRI risk-taking task (BART) and reported their tendencies for risky decision-making using a self-report questionnaire. Puberty was assessed through self-reported pubertal status and salivary testosterone levels. Testosterone concentration, but not physical pubertal status, was positively correlated with self-reported risk-taking behaviour, while neither was correlated with BART performance. Across the whole sample, participants had greater activation of the bilateral nucleus accumbens and right caudate on trials when they made a successful risky decision compared to trials when they made a safe choice or when their risky decision was unsuccessful. There was a negative correlation between pubertal stage and brain activation during unsuccessful risky decision-making trials compared within unsuccessful control trials. Males at a lower stage of pubertal development showed increased activation in the left insula, right cingulate cortex, dorsomedial prefrontal cortex (dmPFC), right putamen and right orbitofrontal cortex (OFC) relative to more pubertally mature males during trials when they chose to take a risk and the balloon popped compared to when they watched the computer make an unsuccessful risky decision. Less pubertally mature males also showed greater activation in brain regions including the dmPFC, right temporal and frontal cortices, right OFC, right hippocampus and occipital cortex in unsuccessful risky trials compared to successful risky trials. These results suggest a puberty-related shift in neural activation within key brain regions when processing outcomes of risky decisions, which may reduce their sensitivity to negative feedback, and in turn contribute to increases in adolescent risk-taking behaviours

The Developmental Mismatch in Structural Brain Maturation during Adolescence

Regions of the human brain develop at different rates across the first two decades of life, with some maturing before others. It has been hypothesized that a mismatch in the timing of maturation between subcortical regions (involved in affect and reward processing) and prefrontal regions (involved in cognitive control) underlies the increase in risk-taking and sensation-seeking behaviors observed during adolescence. Most support for this 'dual systems' hypothesis relies on cross-sectional data, and it is not known whether this pattern is present at an individual level. The current study utilizes longitudinal structural magnetic resonance imaging (MRI) data to describe the developmental trajectories of regions associated with risk-taking and sensation-seeking behaviors, namely, the amygdala, nucleus accumbens (NAcc) and prefrontal cortex (PFC). Structural trajectories of gray matter volumes were analyzed using FreeSurfer in 33 participants aged 7-30 years, each of whom had at least three high-quality MRI scans spanning three developmental periods: late childhood, adolescence and early adulthood (total 152 scans). The majority of individuals in our sample showed relatively earlier maturation in the amygdala and/or NAcc compared to the PFC, providing evidence for a mismatch in the timing of structural maturation between these structures. We then related individual developmental trajectories to retrospectively assessed self-reported risk-taking and sensation-seeking behaviors during adolescence in a subsample of 24 participants. Analysis of this smaller sample failed to find a relationship between the presence of a mismatch in brain maturation and risk-taking and sensation-seeking behaviors during adolescence. Taken together, it appears that the developmental mismatch in structural brain maturation is present in neurotypically developing individuals. This pattern of development did not directly relate to self-reported behaviors at an individual level in our sample, highlighting the need for prospective studies combining anatomical and behavioral measures. © 2014 S. Karger AG, Basel

The relationship between pubertal status and neural activity during risky decision-making in male adolescents

- Purpose: Adolescence is a time of dramatic changes in a range of behaviours, which occur in tandem with changes in brain structure and function. These coincide with the physiological changes of puberty, but little research has focussed on the possible contributing role of puberty. One important behaviour emerging in adolescence is the increased propensity to make risky decisions. A prominent theory to explain this increased propensity for risk is the ‘dual systems’ model (Casey et al., 2008), where risky decisions result from a dissociation in the timing of the maturation of the limbic system and the prefrontal cortex, both regions involved in risky decision-making. The limbic system (incorporating the ventral striatum) is hypothesised to mature relatively early in adolescence, and is thought to be related to pubertal maturation. In contrast, the prefrontal cortex is thought to undergo more protracted development throughout adolescence. This study explores how developmental changes in brain function when performing a risk-taking fMRI (functional Magnetic Resonance Imaging) task are related to puberty, independently of chronological age. - Methods: Forty-five male participants aged 13-14 years underwent fMRI scanning whilst performing a risk-taking task (BART task, adapted from Lejuez et al., 2002). In this age range, there is normal variability in pubertal development, with individuals being at all stages of puberty from pre-puberty to having completed puberty. In the BART task, participants had to decide whether to inflate a virtual balloon on a screen. Successful inflation of the balloon resulted in the opportunity to earn more money, but risked the balloon popping and the money being lost. Stopping allowed the participants to save the money towards their final earnings. Participants completed four six-minute runs of the task. Pubertal stage was assessed using self-report measures including a pictorial Tanner stage and the Pubertal Developmental Scale (Petersen et al., 1988). Salivary hormone levels were collected to measure levels of Testosterone, Oestradiol and DHEA. Participants also completed validated self-report questionnaires of risk-taking, impulsivity and sensation-seeking. - Results: The analysis focused on a main effect, across the entire group, of active decision-making compared to the control condition in regions including the prefrontal cortex and limbic system, which are known to be involved in risky decision-making. We also investigated whether this activation was differentially related to puberty across regions, using both group-wise and regression analyses. - Conclusions; This study investigated a role for puberty in the functional development of brain regions involved in risky decision-making in males, and further informs the usefulness of the dual systems model of risk taking during adolescence

Why a developmental perspective is critical for understanding human cognition

The evidence that Anderson (2014) marshals in support of his theory of neural reuse is persuasive. However, his theoretical framework currently lacks a developmental dimension. We argue that an account of the fundamental aspects of developmental change, as well as the temporal context within which change occurs, would greatly enhance Anderson's theory

Is earlier obesity associated with poorer executive functioning later in childhood? Findings from the Millennium Cohort Study

BACKGROUND: Children affected with overweight or obesity have been associated with having lower educational achievement compared to peers who are non-overweight/obese. One of the drivers of this association could be a link between obesity and poorer executive function. Evidence is limited to small, cross-sectional studies which lack adjustment for important common causes. OBJECTIVE: We investigate the association between weight status and executive function longitudinally in mid-childhood, accounting for potential common causes. METHODS: Linear regression analyses were conducted to examine associations between weight status between 5 and 7 years and executive functioning at 11 years in members of the Millennium Cohort Study (n = 7739), accounting for a wide range of potential common causes. Age- and sex-specific International Obesity Taskforce cut-points for body mass index (BMI) were used. Executive function, including decision-making, impulsivity and spatial working memory, was assessed using the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no unadjusted associations between weight status and decision-making or impulsivity. After adjustment for all potential common causes, there was a lack of consistent evidence to support an association between persistent obesity (including overweight) between 5 and 7 years and spatial working memory task at 11 years. CONCLUSIONS: We found little evidence that poorer spatial working memory contributes to the association of children with obesity having lower educational achievement

Growth and adrenarche: findings from the CATS observational study

BACKGROUND: There is increasing evidence that patterns of pubertal maturation are associated with different patterns of health risk. This study aimed to explore the associations between anthropometric measures and salivary androgen concentrations in pre-adolescent children. METHODS: We analysed a stratified random sample (N=1151) of pupils aged 8-9 years old from 43 primary schools in Melbourne, Australia from the Childhood to Adolescence Transition Study. Saliva samples were assayed for dehydroepiandrosterone (DHEA), DHEA-sulfate and testosterone. Anthropometric measures included height, weight, body mass index (BMI) and waist circumference. Associations between (1) anthropometric measures and each androgen, and (2) hormone status with obesity and parental report of pubertal development were investigated using linear regression modelling with general estimating equations. RESULTS: Greater height, weight, BMI and waist circumference were positively associated with higher androgen concentrations, after adjusting for sex and socioeconomic status. Being overweight or obese was associated with higher testosterone and DHEA concentrations compared with the normal BMI category. Those who were obese were more likely (OR=2.7, 95% CI 1.61 to 4.43, p<0.001) to be in the top tertile of age-adjusted androgen status in both sexes. CONCLUSION: This study provides clear evidence for an association between obesity and higher androgen levels in mid-childhood. The adrenal transition may be a critical time period for weight management intervention strategies in order to manage the risk for metabolic problems in later life for high-risk individuals

Modelling timing and tempo of adrenarche in a prospective cohort study

To better understand how health risk processes are linked to adrenarche, measures of adrenarcheal timing and tempo are needed. Our objective was to describe and classify adrenal trajectories, in terms of timing and tempo, in a population of children transitioning to adolescence with repeated measurements of salivary dehydroepiandrosterone (DHEA), DHEAsulphate, and testosterone. We analysed data from the Childhood to Adolescence Transition Study (CATS), a longitudinal study of 1239 participants, recruited at 8-9 years old and followed up annually. Saliva samples were assayed for adrenal hormones. Linear mixedeffect models with subject-specific random intercepts and slopes were used to model longitudinal hormone trajectories by sex and derive measures of adrenarcheal timing and tempo. The median values for all hormones were higher at each consecutive study wave for both sexes, and higher for females than males. For all hormones, between-individual variation in hormone levels at age 9 (timing) was moderately large and similar for females and males. Between-individual variation in hormone progression over time (tempo) was of moderate magnitude compared with the population average age-slope, which itself was small compared with overall hormone level at each age. This suggests that between-individual variation in tempo was less important for modelling hormone trajectories. Between-individual variation in timing was more important for determining relative adrenal hormonal level in childhood than tempo. This finding suggests that adrenal hormonal levels at age 8-9 years can be used to predict relative levels in early adolescence (up to 13 years)