Active (or REM) sleep is an abundant and ubiquitous feature of mammalian life early in development: Human newborns sleep 16 hours each day and 8 of those hours are spent in active sleep. The relatively high proportion of active sleep in early development inspired the hypothesis that active sleep is important for early brain development. But what is it about active sleep that might make it especially important for brain development? One feature, especially notable in newborns, is the abundant phasic activity that characterizes active sleep, comprising twitches of the limbs, head, face, and eyes. Over the past decade, research in infant rats has demonstrated that sensory feedback from twitching limbs triggers pronounced activity throughout the brain, including events (called spindle bursts) in sensorimotor cortex. Moreover, in a first-ever systematic study focusing on twitching in human infants, the PI and Co-I found abundant twitching in human infants that parallels that seen in rats. In addition to finding that human infants produce dozens of twitches per hour, they also found that patterns of twitching evolve differently in distinct muscle groups, thus supporting the notion that twitching reflects the neurological development of specific action systems. As proposed here, the next step is to determine whether twitches trigger brain activity in newborns and whether this twitch-dependent activity persists over the early postnatal period: This step is essential for determining whether there may be diagnostic and explanatory value in monitoring and assessing twitching in human newborns. Accordingly, this proposal combines behavioral analysis, motion sensing, electrooculography (EOG), and high-density electroencephalography (EEG) in sleeping human infants monitored cross-sectionally at 2 weeks and 1, 2, 3, 4, 5, and 6 months of age.
Specific Aim 1 focuses on whether twitches of the arms and legs trigger EEG events in topographically appropriate regions of sensorimotor cortex. In addition, one of the analytical challenges of this proposal is to determine whether twitch-triggered cortical events can be detected if, as expected, background EEG activity increasingly obscures them over the first six months.
Specific Aim 2 parallels the first but focuses on twitches of the facial muscles (e.g., mouth, cheeks) and associated rapid eye movements (measured using EOG). One major outcome of this aim will be to place the facial sensorimotor system within a broader context that will allow comparisons with sensorimotor development in the limbs. Overall, the work proposed here will lay a foundation for understanding the role that sleep plays in the developmental origins of the sensorimotor deficits that are known to accompany many neurodevelopmental disorders (e.g., cerebral palsy, autism). Ultimately, this research may lead us toward an understanding of how sleep deprivation or restriction (resulting from malnutrition, environmental factors, or neglect) can initiate a cascade of effects that begins with sensorimotor development and continues on to impair cognitive and emotional development.

Public Health Relevance

to public health. Spontaneous activity is one of the defining features of early life in humans and is thought to contribute critically to the healthy development of the visual and auditory systems. In the sensorimotor system, the most abundant spontaneous activity occurs during REM sleep in the form of myoclonic twitches of the arms and legs, fingers and toes, and face and eyes. Nonetheless, these movements? and their effects on brain activity?have never been systematically investigated in human infants, though they may provide critical insights into the processes that drive typical development as well as the sensorimotor deficits that characterize such neurodevelopmental disorders as autism and schizophrenia.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
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Miller, Brett
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University of Iowa
Schools of Arts and Sciences
Iowa City
United States
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