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.

Studies show that abuse, neglect or trauma during childhood can lead to lifelong struggles including with mental health. Fortunately research also indicates that solutions and interventions at various stages of life can be developed to help. But even among people who remain resilient or do not experience acute stresses, a lack of opportunity early in life due to poverty or systemic racism can still constrain their ability to realize their full potential. In what ways are health and other outcomes affected by early life difficulty? What can individuals and institutions do to enhance opportunity?" "This daylong event will feature talks by neuroscientists, policy experts, physicians, educators and activists as they discuss how our experiences and biology work together to affect how our minds develop and what can be accomplished in helping people overcome early disadvantages.

Focal Cortical Dysplasia (FCD) is the most common focal cortical malformation leading to intractable childhood focal epilepsy. In recent years, we and others have shown that FCD type II is caused by mosaic mutations in genes within the PI3K-AKT-mTOR-signaling pathway. Hyperactivation of the mTOR pathway accounts for neuropathological abnormalities and seizure occurrence in FCD. We further showed from human surgical FCDII tissue that epileptiform activity correlates with the density of mutated dysmorphic neurons, supporting their pro-epileptogenic role. The level of mosaicism, as defined by variant allele frequency (VAF) is thought to correlate with the size and regional brain distribution of the lesion such that when a somatic mutation occurs early during the cortical development, the dysplastic area is smaller than if it occurs later. Novel approaches based on the detection of cell-free DNA from the CSF and from trace tissue adherent to SEEG electrodes promise future opportunities for genetic testing during the presurgical evaluation of refractory epilepsy patients or in those that are not eligible for surgery. In utero-based electroporation mouse models allow to express somatic mutation during neurodevelopment and recapitulate most neuropathological and clinical features of FCDII, establishing relevant preclinical mouse models for developing precision medicine strategies.

We all have a sense of time. Yet it is a particularly intangible sensation. So how is our “sense” of time represented in the brain? Functional neuroimaging studies have consistently identified a network of regions, including Supplementary Motor Area and basal ganglia, that are activated when participants make judgements about the duration of currently unfolding events. In parallel, left parietal cortex and cerebellum are activated when participants predict when future events are likely to occur. These structures are activated by temporal processing even when task goals are purely perceptual. So why should the perception of time be represented in regions of the brain that have more traditionally been implicated in motor function? One possibility is that we learn about time through action. In other words, action could provide the functional scaffolding for learning about time in childhood, explaining why it has come to be represented in motor circuits of the adult brain.

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.

Whilst epilepsy may be a consequence of an acquired insult including trauma, stroke, and brain tumours, the genetic component to epilepsies has been greatly under-estimated. Considerable progress has recently occurred in the understanding of epilepsy genetics, both at a clinical genetic level and in the basic science of epilepsies. The clinical evidence for genetic components will be first briefly discussed including data from population studies, twin analyses and multiplex family studies. Initial molecular discoveries occurred via classical methods of linkage and gene identification. Recent large-scale hypothesis-free whole exome studies searching for rare variants and genome-wide association studies detecting common variants have been very rewarding. These discoveries have now impacted on clinical practice, especially in severe childhood epilepsies but increasingly so in adult patients. The “genetic background” of patients has long been posited as part of the reason that some patients have epilepsy, or perhaps why some have more severe epilepsy. This has been unmeasurable but now, with the development of polygenic risk scores, the “background” is now in the research foreground. The current and future impact of polygenic risk scores will be explored.

Evidence-based education programmes, like many clinical interventions, are multi-faceted and can be expensive to implement. In this talk I will describe an alternative: distilling the common elements across many evidence-based programmes. Published programme manuals are selected through systematic review, then extensively coded and cross-referenced. Finally, the common elements that emerge are shared with practitioners as part of a ‘library’ of practices (rather than a holistic programme manual). Although the common elements methodology has been used in the prevention and intervention sciences, this project reflects the first attempt at applying this approach to early childhood education. I will describe the common elements methods and preliminary findings from our Nuffield-funded project, in collaboration with the Early Intervention Foundation. I will discuss the challenges and opportunities we have encountered, alongside our strategies for sharing evidence with practitioners in a digestible way.

Malformations of cortical development (MCDs) result from alterations of one or combined developmental steps, including progenitors proliferation, neuronal migration and differentiation. They are important cause of childhood epilepsy and frequently associate cognitive deficits and behavioral alterations. Though the genetic basis of MCDs have known prominent progress during the past decade, including the identification of somatic, mosaic mutations responsible for focal MCDs, the pathophysiological mechanisms linking malformations to epileptogenesis remain elusive. In this seminar I will present data from my team and from the literature addressing this topic in two different MCDs types, the subcortical band heterotopia as a model of cortical migration defect and mTOR- dependent MCDs , that characterize by cortical dyslamination and neuronal differentiation defects.

I will begin by describing recent research taking a new, model-based approach to perceptual development. This approach uncovers fundamental changes in information processing underlying the protracted development of perception, action, and decision-making in childhood. For example, integration of multiple sensory estimates via reliability-weighted averaging – widely used by adults to improve perception – is often not seen until surprisingly late into childhood, as assessed by both behaviour and neural representations. This approach forms the basis for a newer question: the scope for the nervous system to deploy useful computations (e.g. reliability-weighted averaging) to optimise perception and action using newly-learned sensory signals provided by technology. Our initial model system is augmenting visual depth perception with devices translating distance into auditory or vibro-tactile signals. This problem has immediate applications to people with partial vision loss, but the broader question concerns our scope to use technology to tune in to any signal not available to our native biological receptors. I will describe initial progress on this problem, and our approach to operationalising what it might mean to adopt a new signal comparably to a native sense. This will include testing for its integration (weighted averaging) alongside the native senses, assessing the level at which this integration happens in the brain, and measuring the degree of ‘automaticity’ with which new signals are used, compared with native perception.

Though studies show that abuse, neglect or trauma during childhood can lead to lifelong lifelong struggles including in mental health, research also indicates that solutions and interventions at various stages of life can be developed to help. And while many people manage to remain resilient, a lack of opportunity early in life, including because of poverty and systemic racism, can constrain their ability to realize their full potential. In what ways are health and other outcomes affected? How can systems instead restore opportunity? "The Picower Institute for Learning and Memory's biennial spring symposium, 'Early Life Stress & Mental Health,' will examine these issues. The daylong event will feature talks by neuroscientists, policy experts, physicians, educators and activists as they discuss how our experiences and biology work together to affect how our minds develop and what can be accomplished in helping people overcome early disadvantages.

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 emergence of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms govern the diversity of these developmental processes? There are many existing descriptive theories, but to date none are computationally formalized. We provide a mathematical framework that specifies the growth of a brain network over developmental time. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over development. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the developmental simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity of childhood brain development, capable of integrating different levels of analysis – from genes to cognition. (Pre-print: https://www.biorxiv.org/content/10.1101/2020.08.13.249391v1)

The human cortical ribbon varies during the lifespan, from childhood to senescence. To study the effects of genetic and environmental factors on these dynamics, one needs to measure specific phenotypes (cortical volume, surface area, thickness, new neuroimaging phenotypes such as intracortical myelination or multimodal ones based on their combination, or their asymmetries) that characterize the cerebral grey matter accurately

Narratives of human evolution have focused on cortical expansion and increases in brain size relative to body size, but considered that changes in life history, such as in age at sexual maturity and thus the extent of childhood and maternal dependence, or maximal longevity, are evolved features that appeared as consequences of selection for increased brain size, or increased cognitive abilities that decrease mortality rates, or due to selection for grandmotherly contribution to feeding the young. Here I build on my recent finding that slower life histories universally accompany increased numbers of cortical neurons across warm-blooded species to propose a simpler framework for human evolution: that slower development to sexual maturity and increased post-maturity longevity are features that do not require selection, but rather inevitably and immediately accompany evolutionary increases in numbers of cortical neurons, thus fostering human social interactions and cultural and technological evolution as generational overlap increases.

Historically pregnant women and their unborn baby have been amongst those with the poorest outcomes in previous epidemics, most notably the Zika virus. For much of 2020, with the emergence of the novel coronavirus, the effect on the fetus remains unclear. While initial reports suggest that vertical transmission with SARS-CoV2 is reassuringly rare, the complex socioeconomic, domestic and broader maternal lifestyle factors which can influence a child’s lifelong well-being have been modulated during the experience of this pandemic. The developing brain is particularly susceptible to maternal stress, resulting in permanent structural changes and increased incidence of behavioural and mental health illness later in childhood. A large international longitudinal survey is being undertaken by the Department of Psychology to better understand the impact of the pandemic on those yet to be born.

I argue that the evolution of our life history, with its distinctively long, protected human childhood allows an early period of broad hypothesis search and exploration, before the demands of goal-directed exploitation set in. This cognitive profile is also found in other animals and is associated with early behaviours such as neophilia and play. I relate this developmental pattern to computational ideas about explore-exploit trade-offs, search and sampling, and to neuroscience findings. I also present several lines of new empirical evidence suggesting that young human learners are highly exploratory, both in terms of their search for external information and their search through hypothesis spaces. In fact, they are sometimes more exploratory than older learners and adults.

We will start our talk with a short video of our research, illustrating methods (some old and new) and findings that have provided our current understanding of how visual capabilities develop in infancy and early childhood. However, our research poses some outstanding questions. We will briefly discuss three issues, which are linked by a common focus on the development of visual attentional processing: (1) How do recurrent cortical loops contribute to development? Cortical selectivity (e.g., to orientation, motion, and binocular disparity) develops in the early months of life. However, these systems are not purely feedforward but depend on parallel pathways, with recurrent feedback loops playing a critical role. The development of diverse networks, particularly for motion processing, may explain changes in dynamic responses and resolve developmental data obtained with different methodologies. One possible role for these loops is in top-down attentional control of visual processing. (2) Why do hyperopic infants become strabismic (cross-eyes)? Binocular interaction is a particularly sensitive area of development. Standard clinical accounts suppose that long-sighted (hyperopic) refractive errors require accommodative effort, putting stress on the accommodation-convergence link that leads to its breakdown and strabismus. Our large-scale population screening studies of 9-month infants question this: hyperopic infants are at higher risk of strabismus and impaired vision (amblyopia and impaired attention) but these hyperopic infants often under- rather than over-accommodate. This poor accommodation may reflect poor early attention processing, possibly a ‘soft sign’ of subtle cerebral dysfunction. (3) What do many neurodevelopmental disorders have in common? Despite similar cognitive demands, global motion perception is much more impaired than global static form across diverse neurodevelopmental disorders including Down and Williams Syndromes, Fragile-X, Autism, children with premature birth and infants with perinatal brain injury. These deficits in motion processing are associated with deficits in other dorsal stream functions such as visuo-motor co-ordination and attentional control, a cluster we have called ‘dorsal stream vulnerability’. However, our neuroimaging measures related to motion coherence in typically developing children suggest that the critical areas for individual differences in global motion sensitivity are not early motion-processing areas such as V5/MT, but downstream parietal and frontal areas for decision processes on motion signals. Although these brain networks may also underlie attentional and visuo-motor deficits , we still do not know when and how these deficits differ across different disorders and between individual children. Answering these questions provide necessary steps, not only increasing our scientific understanding of human visual brain development, but also in designing appropriate interventions to help each child achieve their full potential.

Dravet syndrome is a severe childhood epilepsy due to heterozygous loss-of-function mutation of the gene SCN1A, which encodes the type 1 neuronal voltage gated sodium (Na+) channel alpha-subunit Nav1.1. Prior studies in mouse models of Dravet syndrome (Scn1a+/- mice) at early developmental time points indicate that, in cerebral cortex, Nav1.1 is predominantly expressed in GABAergic interneurons (INs) and, in particular, in parvalbumin-positive fast-spiking basket cells (PV-INs). This has led to a model of Dravet syndrome pathogenesis whereby Nav1.1 mutation leads to preferential IN dysfunction, decreased synaptic inhibition, hyperexcitability, and epilepsy. We found that, at later developmental time points, the intrinsic excitability of PV-INs has essentially normalized, via compensatory reorganization of axonal Na+ channels. Instead, we found persistent and seemingly paradoxical dysfunction of putative disinhibitory INs expressing vasoactive intestinal peptide (VIP-INs). In vivo two-photon calcium imaging in neocortex during temperature-induced seizures in Scn1a+/- mice showed that mean activity of both putative principal cells and PV-INs was higher in Scn1a+/- relative to wild-type controls during quiet wakefulness at baseline and at elevated core body temperature. However, wild-type PV-INs showed a progressive synchronization in response to temperature elevation that was absent in PV-INs from Scn1a+/- mice immediately prior to seizure onset. We suggest that impaired PV-IN synchronization, perhaps via persistent axonal dysfunction, may contribute to the transition to the ictal state during temperature induced seizures in Dravet syndrome.