Our ability to remember past events and experiences lies at the core of cognition and behaviour. But how do fleeting moments get converted into durable memory traces? Recent work has highlighted the pivotal role of post-learning sleep for successful memory consolidation, the process of stabilising new memories over time. However, little is known about the neurophysiological mechanisms through which the sleeping brain consolidates new memories. Not only has this left a gap in our understanding of memory formation as a whole, but also the means to modulate memories during sleep have remained underexplored. SPIN will test the exciting hypothesis that particular electrophysiological signatures of sleep, namely sleep spindles, are the mechanistic vehicle driving memory consolidation. Specifically, I hypothesise that in coordination with hippocampal reactivation events, sleep spindles are deployed to cortical learning sites where they induce lasting structural changes. Using intracranial recordings from the human hippocampus (measuring single neuron firing and associated ‘ripple’ oscillations) and from an array of cortical areas, we will first establish whether spindles are temporally aligned with hippocampal reactivation events. Next, we will use high-density scalp EEG and functional as well as structural MRI in healthy participants to test whether spindle deployment to cortical learning sites predicts structural changes in these regions. To assert causality, we will examine the effects of invasive spindle perturbation in patients on memory consolidation. Finally, we will experimentally enhance local spindles to harness their potential as a tool for boosting human memory. In sum, SPIN will use an unprecedented array of human brain recording and stimulation techniques to provide a mechanistic link between learning, sleep and structural brain changes, culminating in novel tools to enhance human learning and memory.

Early adolescence is a key window for human development. Strategic timing of interventions during this life stage may seize opportunities and prevent risks; bolster the impact of earlier investments; and ease damages from previous adversity. Yet evidence on whether such programs can fulfil this potential, for which children, and through which channels, is scant, especially in low-resource settings, where 90% of the world’s 1.2 billion adolescents live. I will tackle these gaps by relying on a cohort of ~2,500 children approaching early adolescence. In 2015, this sample participated in a trial evaluating quality preschool education in Ghana and has been followed-up since: the program improved child development through middle childhood. I will re-randomise this sample at 12 years to test a parenting skills program to enhance early adolescent development through improved parenting support and parent-adolescent interactions. Children and parents will be re-interviewed when children are 13, 15, and 17 years through mixed-method data collection. Outcomes include adolescent social-emotional and academic skills, health (including stress biomarkers), and adult-life transitions. This data will allow testing dynamic complementarities between interventions during early childhood and early adolescence, or whether interventions in adolescence might compensate for earlier adversity in the short- and longer-term. Methodologically, these questions can be convincingly studied only if data are available for the same individuals over time, and if variations in exposure to early childhood and early adolescence programs are exogenously driven. This is the first study that addresses both requirements, providing a breakthrough. Heterogeneity by child gender and socioeconomic status, and mechanisms are further research foci. LEAD’s high-risk components are well-balanced by my in-depth knowledge of the field, methods, and study context, with high potential for scientific and societal impact.