Over the last decade, research on curiosity – the desire to seek new information – has been rapidly growing. Several studies have shown that curiosity elicits activity within the dopaminergic circuit and thereby enhances hippocampus-dependent learning. However, given this new field of research, we do not have a good understanding yet of (i) how curiosity-based learning changes across the lifespan, (ii) why some people show better learning improvements due to curiosity than others, and (iii) whether lab-based research on curiosity translates to how curiosity affects information seeking in real life. In this talk, I will present a series of behavioural and neuroimaging studies that address these three questions about curiosity. First, I will present findings on how curiosity and interest affect learning differently in childhood and adolescence. Second, I will show data on how inter-individual differences in the magnitude of curiosity-based learning depend on the strength of resting-state functional connectivity within the cortico-mesolimbic dopaminergic circuit. Third, I will present findings on how the level of resting-state functional connectivity within this circuit is also associated with the frequency of real-life information seeking (i.e., about Covid-19-related news). Together, our findings help to refine our recently proposed framework – the Prediction, Appraisal, Curiosity, and Exploration (PACE) framework – that attempts to integrate theoretical ideas on the neurocognitive mechanisms of how curiosity is elicited, and how curiosity enhances learning and information seeking. Furthermore, our findings highlight the importance of curiosity research to better understand how curiosity can be harnessed to improve learning and information seeking in real life.

My research focuses broadly on the lifelong health disparities associated with experiences of adversity early in life. In this talk I will present the results of our recently completed Teen Resilience Project, a prospective and longitudinal study of first onset depression during adolescence. First, I will present the results on whether and how inflammatory processes may be shaped by early life adversity. Second, I will present data on the role of stress-induced inflammation in reward-related psychological processes. Finally, I will discuss the biobehavioral predictors of first-onset depression in this sample.

Abuse, neglect, and other forms of uncontrollable stress during childhood and early adolescence can lead to adverse outcomes later in life, including especially perturbations in the regulation of mood and emotional states, and specifically anxiety disorders and depression. However, stress experiences vary from one individual to the next, meaning that causal relationships and mechanistic accounts are often difficult to establish in humans. This interdisciplinary talk considers the value of research in experimental animals where stressor experiences can be tightly controlled and detailed investigations of molecular, cellular, and circuit-level mechanisms can be carried out. The talk will focus on the widely used repeated maternal separation procedure in rats where rat offspring are repeatedly separated from maternal care during early postnatal life. This early life stress has remarkably persistent effects on behaviour with a general recognition that maternally-deprived animals are susceptible to depressive-like phenotypes. The validity of this conclusion will be critically appraised with convergent insights from a recent longitudinal study in maternally separated rats involving translational brain imaging, transcriptomics, and behavioural assessment.

Normative development in adolescence indicates that the prefrontal cortex is still under development thereby unable to exert efficient top-down inhibitory control on subcortical regions such as the basolateral amygdala and the nucleus accumbens. This imbalance in the developmental trajectory between cortical and subcortical regions is implicated in expression of the prototypical impulsive, compulsive, reward seeking and risk-taking adolescent behavior. Here we demonstrate that a chronic mild unpredictable stress procedure during adolescence in male Wistar rats arrests the normal behavioral maturation such that they continue to express adolescent-like impulsive, hyperactive, and compulsive behaviors into late adulthood. This arrest in behavioral maturation is associated with the hypoexcitability of prelimbic cortex (PLC) pyramidal neurons and reduced PLC-mediated synaptic glutamatergic control of BLA and nucleus accumbens core (NAcC) neurons that lasts late into adulthood. At the same time stress exposure in adolescence results in the hyperexcitability of the BLA pyramidal neurons sending stronger glutamatergic projections to the NAcC. Chemogenetic reversal of the PLC hypoexcitability decreased compulsivity and improved the expression of goal-directed behavior in rats exposed to stress during adolescence, suggesting a causal role for PLC hypoexcitability in this stress-induced arrested behavioral development. (https://www.biorxiv.org/content/10.1101/2021.11.21.469381v1.abstract)

Macroscopic brain organisation emerges early in life, even prenatally, and continues to develop through adolescence and into early adulthood. The emergence and continual refinement of large-scale brain networks, connecting neuronal populations across anatomical distance, allows for increasing functional integration and specialisation. This process is thought crucial for the emergence of complex cognitive processes. But how and why is this process so diverse? We used structural neuroimaging collected from a large diverse cohort, to explore how different features of macroscopic brain organisation are associated with diverse cognitive trajectories. We used diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child's connectome revealed that some brain networks were strongly organized around highly connected 'hubs'. The more children's brains were critically dependent on hubs, the better their cognitive skills. Conversely, having poorly integrated hubs was a very strong risk factor for cognitive and learning difficulties across the sample. We subsequently developed a computational framework, using generative network modelling (GNM), to model the emergence of this kind of connectome organisation. Relatively subtle changes within the wiring rules of this computational framework give rise to differential developmental trajectories, because of small biases in the preferential wiring properties of different nodes within the network. Finally, we were able to use this GNM to implicate the molecular and cellular processes that govern these different growth patterns.

Mental Health problems among youth constitutes an area of significant social, educational, clinical, policy and public health concern. Understanding processes and mechanisms that underlie the development of mental health problems during childhood and adolescence requires theoretical and methodological integration across multiple scientific domains, including developmental science, neuroscience, genetics, education and prevention science. The primary focus of this presentation is to examine the relative role of genetic and family environmental influences on children’s emotional and behavioural development. Specifically, a complementary array of genetically sensitive and longitudinal research designs will be employed to examine the role of early environmental adversity (e.g. inter-parental conflict, negative parenting practices) relative to inherited factors in accounting for individual differences in children’s symptoms of psychopathology (e.g. depression, aggression, ADHD ). Examples of recent applications of this research to the development of evidence-based intervention programmes aimed at reducing psychopathology in the context of high-risk family settings will also be presented.

The microbiota-gut-brain axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour during early life, adolescence & ageing. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. Studies in animal models have shown that the development of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics. Recently, the gut microbiota has been implicated in regulating the stress response, and social behaviour. Moreover, fundamental brain processes from adult hippocampal neurogenesis to myelination to microglia activation have been shown to be regulated by the microbiome. Further studies will focus on understanding the mechanisms underlying such brain effects and how they can be exploited by microbiota-targeted interventions including ‘psychobiotics’ and diet

Although substance use disorders (SUDs) occur commonly in patients with schizophrenia and significantly worsen their clinical course, the neurobiological basis of SUDs in schizophrenia is not well understood. Therefore, there is a critical need to understand the mechanisms underlying SUDs in schizophrenia in order to identify potential targets for therapeutic intervention. Since drug use usually begins in adolescence, it is also important to understand the long-term effects of adolescent drug exposure on schizophrenia- and reward- related behaviors and circuitry. This talk will combine pharmacological, behavioral, electrophysiologic (local field potential recordings) and pre-clinical magnetic resonance imaging (resting-state functional connectivity and magnetic resonance spectroscopy) approaches to study these topics with an eye toward developing better treatment approaches.

Adolescence is a period of life characterised by heightened sensitivity to social stimuli, an increased need for peer interaction and peer acceptance, and development of the social brain. Lockdown and social distancing measures intended to mitigate the spread of COVID-19 are reducing the opportunity to engage in face-to-face social interaction with peers. The consequences of social distancing on human social brain and social cognitive development are unknown, but animal research has shown that social deprivation and isolation have unique effects on brain and behaviour in adolescence compared with other stages of life. It is possible that social distancing might have a disproportionate effect on an age group for whom peer interaction is a vital aspect of development.