Nora Moog, Ph.D., Charité – Universitätsmedizin Berlin, Berlin, Germany (Chair)
Katharina Pittner, Ph.D, Charité – Universitätsmedizin Berlin, Berlin, Germany (Co-Chair)
Sleep is an important factor for healthy brain functioning and disrupted sleep is a common feature of neurodevelopmental and psychiatric disorders. The role of early life sleep and its maturational process influencing brain development and long-term social, emotional and cognitive function is still poorly understood. In this symposium we explore the physiological maturation and environmental determinants of early life sleep as well as the neurobiological and behavioral consequences of variation in sleep quality across different species. In the first presentation, Dr. Sarah Schoch will show the link between sleep behavior, sleep EEG, gut microbiota, and infant behavioral development in a sample of 162 healthy human infants across the first year of life. In another infant cohort, Dr. Katharina Pittner will explore the prospective association between trajectories of sleep quality across the first year of life and cortical white matter development at 1 year of age. Next, Dr. Donald Wilson will present his work on two rodent models of early life adversity-induced sleep impairments and their consequences for GABAergic cells in the CNS as well as behavior and cognitive function. In the last presentation, Dr. Miranda Lim will examine the correspondence between prefrontal functional alterations resulting from early life sleep disruption and aberrant social behavior in the highly social prairie vole. Finally, Dr. Nora Moog will serve as the symposium discussant, facilitating discussion on how we can increase our understanding of what constitutes high quality sleep in early life and how we can promote it. This symposium combines studies investigating normal variation in sleep patterns with studies performing experimental manipulation of sleep early in life and integrates research exploring multiple physiological and behavioral systems with different research techniques (e.g. EEG, MRI) and across different species.
List of abstracts and presenters:
ASSOCIATIONS OF EARLY HUMAN SLEEP BEHAVIOR, SLEEP EEG, AND GUT MICROBIOTA WITH BEHAVIORAL DEVELOPMENT
Sarah F. Schoch, Ph.D.
University Hospital Zurich, Switzerland, Donders Institute, Nijmegen, Netherlands
The maturation of different physiological processes drives healthy infant development. Two critical maturation processes are the evolution of sleep rhythms and the growth of a complex ecosystem of gut microbiota. Previous studies have shown a bi-directional link between sleep and gut microbiota in animal models and human adults. Here, we present data from 162 healthy human infants tracked across the first year of life to show how sleep behavior, sleep EEG, gut microbiota, and infant behavioral development are linked together. Our previous work has demonstrated the emergence of a sleep-gut link in early infancy. Both sleep behavior and sleep EEG markers show a dynamic association with gut microbial markers with a potential early sensitive period (Schoch et al 2022 – Progress in Neurobiology). Furthermore, we will present ongoing work on how infant day-to-day sleep behavior is linked to sleep neurophysiology. We will show that daytime napping is associated with nighttime slow wave activity, nighttime movement is associated with spindle activity, and sleep timing is associated with brain connectivity during sleep. Lastly, we will present data on how sleep behavior, the sleep EEG, and gut microbiota are associated with concurrent and prospective behavioral development as measured by the Ages and Stages Questionnaire.
Support: University of Zurich (Clinical Research Priority Program “Sleep and Health”, Forschungskredit FK-18-047, Faculty of Medicine), the Swiss National Science Foundation (PCEFP1-181279, P0ZHP1-178697), Foundation for Research in Science and the Humanities (STWF-17-008), and the Olga Mayenfisch Stiftung.
SLEEP ACROSS THE FIRST YEAR OF LIFE IS ASSOCIATED WITH WHITE MATTER VOLUME AT 12 MONTHS
Katharina Pittner, Ph.D, Charité – Universitätsmedizin Berlin, Berlin, Germany
During the first year of life, infants spend more time asleep than awake suggesting that sleep serves a crucial function in development. However, there is considerable variation in sleep quality. Moreover, infancy is the postnatal period during which the brain undergoes the most rapid and substantial developmental changes. During the first 12 months, the total brain volume doubles, surface area increases by almost 80%, and the rate of white matter myelination peaks. Animal research suggests that the disruption of early sleep negatively affects the brain but evidence on the association between sleep and brain development in humans is mostly lacking. We will present findings from an infant cohort in which total sleep time was assessed with questionnaires at 1-, 3-, 6-, 9-, and 12-mo age. Individual intercepts and slopes across the first year of life for sleep duration were calculated for each infant. Both the sleep intercept as well as the sleep slope were significantly associated with white matter volume at 12-mo age, suggesting that infants with a higher initial sleep duration and whose sleep duration decreased less across the first year tended to have greater white matter volumes at 12-mo age. Gray matter volume at 12-mo age, on the other hand was not associated with sleep intercept or slope.
EARLY LIFE ADVERSE EVENTS IMPACT SLEEP TO MEDIATE LATER LIFE BEHAVIORAL PATHOLOGY
Donald A. Wilson, Ph.D., and Regina M. Sullivan, Ph.D.
Department of Child and Adolescent Psychiatry, NYU School of Medicine USA
Emotional Brain Institute, Nathan Kline institute for Psychiatric Research USA
Early-life adversity is one of the most robust predictors of psychiatric disorders in adolescence and adulthood. Recently, comorbid sleep deficits have been highlighted in adversity-induced psychiatric disorders, and sleep repair significantly reduces symptoms, including in children. Yet, a causal relationship between adversity-induced psychopathology and sleep disruption has not been established. Here, we will present evidence from two distinct rodent models of early life adversity – developmental ethanol exposure and trauma associated with maternal care (low bedding) – demonstrating the impact of such early-life events on sleep, and the role this sleep disruption plays in later life cognitive and emotional dysfunction. Each early-life adverse event impacts sleep in unique impairment clusters, including sleep fragmentation, reduced delta oscillations, and decreased sleep spindle density. These sleep impairments extend into adulthood as an insidious nightly remnant of the developmental adversity. Importantly, our data show sleep disturbances correlate with, and in some cases statistically mediate, behavioral outcomes. For example, trauma-maternal care results in enduring home cage behavioral hyperactivity mediated by. reduced sleep spindle density. Similarly, infant ethanol-exposure induced enduring sleep fragmentation which predicted contextual memory impairment. Finally, both infant adversity models impact GABAergic cell survival and function. Results of selective targeting of circuit-specific GABAergic cells for sleep and behavior will be described.
Supported by R01-AA023181 (DAW) and R37-HD083217 (RMS)
EARLY LIFE SLEEP DISRUPTION ALTERS PREFRONTAL CORTEX AND IMPAIRS BEHAVIOR IN THE HIGHLY SOCIAL PRAIRIE VOLE
Miranda M. Lim, M.D., Ph.D.
Oregon Health & Science University
VA Portland Health Care System, Portland, OR, USA
Sleep is important for brain development, and disrupted sleep early in life is common in developmental disorders, such as autism spectrum disorder. Autistic individuals have difficulty engaging in complex social behaviors. By studying the wild prairie vole, a highly social monogamous rodent, our previous work has shown that early life sleep disruption during a sensitive developmental window results in impaired social bonding between voles in a manner reminiscent of autism (Jones et al 2019 – Science Advances). However, it was previously unknown exactly how poor sleep impacted brain circuits to cause these impairments. To address this gap, we recently showed that early life sleep disruption caused increased dendritic spine density and alterations in synaptic structure within the prefrontal cortex, a late-maturing brain region important for social bonding (Jones et al 2021 – Current Research in Neurobiology). Ongoing work will examine the functional electrophysiological correlates of these structural dendritic changes in relation to aberrant social behavior in real-time. These data advance the hypothesis that one possible function of early life sleep is to ensure the proper development and tuning of neural circuits related to social behavior, and that sleep could represent a modifiable target in the pathogenesis of autism spectrum disorder.
Support: Brain & Behavior Foundation NARSAD Young Investigator Award #23700, NSF NCS Foundations Award #1926818, Portland VA Research Foundation (MML)
Symposium Discussant: Nora Moog, Ph.D., Charité – Universitätsmedizin Berlin, Berlin, Germany