Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but methodological challenges have hindered assessments of this possibility in humans. Here, we delivered a previously learned song and a novel song to 2-year-old toddlers during natural nocturnal sleep and, using functional magnetic resonance imaging, found that hippocampal activation was stronger for the learned song compared with the novel song. This was true regardless of whether the song was presented intact or backwards. Toddlers who remembered where and in the presence of which toy character they heard the song exhibited stronger hippocampal activation for the song. The results establish that hippocampal activation in toddlers reflects past experiences, persists despite some alteration of the stimulus, and is associated with behavior. This research sheds light on early hippocampal and memory functioning and offers an approach to interrogate the neural substrates of early memory.

Episodic memory, or the ability to remember past events with specific detail, is central to the human experience and is related to learning and adaptive functioning in a variety of domains. In typically developing children, episodic memory emerges during infancy and improves during early childhood and beyond. Developmental processes within the hippocampus are hypothesized to be primarily responsible for both the early emergence and persistence of episodic memory in late infancy and early childhood. However, these hypotheses are based on non-human models. In-vivo investigations in early human development of hippocampal processes have been significantly limited by methodological challenges in acquiring neuroimaging data, particularly task-related functional neuroimaging data, from infants and toddlers. Recent studies in adults have shown neural activity in the brain regions supporting episodic memory during slow-wave sleep using functional magnetic resonance imaging (fMRI), and fMRI has been increasingly utilized in infancy and early childhood to address other research questions. We review initial evidence and present preliminary data showing the promise of this approach for examining hippocampal contribution to how infants and toddlers remember individual events, and their association with information about the context in which the event occurred. Overall, our review, integrated with the presentation of some preliminary data provides insight on leveraging sleep to gain new perspectives on early memory functioning.

Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but research in humans has been constrained by the difficulty of examining hippocampal function during early development. In the present study, we assessed 48 2-year-olds with a novel paradigm in which participants completed two games on a tablet that required remembering associations between unique characters, the places they visited, and the temporal order with which they did so. At the completion of each game, a unique, novel song played. Toddlers remembered spatial locations better than temporal order during an immediate test, after a 20-minute delay, and after a week delay. After the last behavioral session, toddlers underwent an fMRI task during natural nocturnal sleep evaluating hippocampal activation in response to learned and novel songs. We found that the extent of hippocampal activation for learned songs compared to novel songs during sleep was correlated with memory for temproal order across all time delays, but not with memory for spatial locations. The results confirm that that the functional contribution of the hippocampus to early memory can be assessed during sleep and suggest that assessment of temporal aspects of memory in the current task best capture this contribution.

Episodic memory, or the ability to remember past events with specific detail, is central to the human experience and is related to learning and adaptive functioning in a variety of domains. In typically developing children, episodic memory emerges during infancy and improves during early childhood and beyond. Developmental processes within the hippocampus are hypothesized to be primarily responsible for both the early emergence and persistence of episodic memory in late infancy and early childhood. However, these hypotheses are based on non-human models. In-vivo investigations in early human development of hippocampal processes have been significantly limited by methodological challenges in acquiring neuroimaging data, particularly task-related functional neuroimaging data, from infants and toddlers. Recent studies in adults have shown neural activity in the brain regions supporting episodic memory during slow-wave sleep using functional magnetic resonance imaging (fMRI), and fMRI has been increasingly utilized in infancy and early childhood to address other research questions. We review initial evidence and present preliminary data showing the promise of this approach for examining hippocampal contribution to how infants and toddlers remember individual events, and their association with information about the context in which the event occurred. Overall, our review, integrated with the presentation of some preliminary data provides insight on leveraging sleep to gain new perspectives on early memory functioning.

The human brain undergoes rapid development during the first years of life. Beginning in utero, a wide array of biological, social, and environmental factors can have lasting impacts on brain structure and function. To understand how prenatal and early life experiences alter neurodevelopmental trajectories and shape health outcomes, several NIH Institutes, Centers, and Offices collaborated to support and launch the HEALthy Brain and Child Development (HBCD) Study. The HBCD Study is a multi-site prospective longitudinal cohort study, that will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Influenced by the success of the ongoing Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) and in partnership with the NIH Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, the HBCD Study aims to establish a diverse cohort of over 7000 pregnant participants to understand how early life experiences, including prenatal exposure to addictive substances and adverse social environments as well as their interactions with an individuals genes, can affect neurodevelopmental trajectories and outcomes. Knowledge gained from the HBCD Study will help identify targets for early interventions and inform policies that promote resilience and mitigate the neurodevelopmental effects of adverse childhood experiences and environments.