Sleep-related behavior and cortical activity in premature human infants as predictors of developmental outcomes.

PROJECT SUMMARY
Sleep permeates our early existence: A typical human newborn sleeps 16 hours each day, evenly divided
between active (REM) sleep and quiet sleep. The relatively high proportion of active sleep in newborns is the
foundation for the decades-old hypothesis that active sleep is important for infant brain development. In
considering this hypothesis, it is important to remember that active sleep is a complex state composed of a
variety of behavioral and physiological components that emerge and coalesce over development. Thus, it may
be that one or more of these components play outsized roles in promoting brain development. One such
candidate component is the phasic activity that comprises twitches of the limbs, face, and eyes. Over the past
15 years, research in infant rats has revealed that sensory feedback from twitching limbs triggers discrete and
abundant activity throughout the sensorimotor system, cascading from the spinal cord to the brainstem,
cerebellum, thalamus, sensorimotor cortex, and hippocampus. In recent years, with funding from the Gates
Foundation and an R21 from NICHD, investigations were extended to full-term human infants over the first seven
postnatal months. Using behavioral measures and high-density electroencephalographic (EEG) recordings, this
research revealed heretofore unknown features about the spatiotemporal organization of infant sleep and
twitching and introduced new developmental milestones and hypotheses. Here, we propose to extend these
efforts to preterm infants for two reasons: Preterm infants exhibit an even higher proportion of active sleep than
newborn full-term infants, and they are at increased risk for deficits in motor skill, cerebral palsy, autism, and
other neurodevelopmental disorders. Thus, we will determine whether twitching can enhance our understanding
of the origins and time course of atypical developmental trajectories and guide future interventions. Very preterm
human infants (<32 weeks postmenstrual age) and mildly preterm infants (32-36 weeks postmenstrual age) in
the neonatal intensive care unit (NICU) in the Stead Family Children’s Hospital at the University of Iowa will be
recruited to participate in a longitudinal study spanning the period before (Phase I) and after (Phase II) discharge
from the NICU. Every two weeks during Phase I, sleep behavior will be recorded along with EEG activity, and
respiratory rate. During Phase II, in the same preterm infants as well as full-term age-matched controls, sleep
behavior, EEG activity, and respiratory rate will be recorded three times between one week and six months
corrected age. Neurobehavioral and motor skill assessments will be performed at one and six months of age
and clinical follow-up assessments will be performed at two years of age. Because this study is longitudinal,
behavioral and physiological sleep data will be compared in the same infants across Phases I and II and related
to developmental outcomes. Ultimately, this project will provide an unprecedented opportunity to understand
how sleep and sleep-related behavior contribute to typical and atypical development in early life.

Grant Number: 5R01HD104616-04
NIH Institute/Center: NIH
Principal Investigator: Mark Blumberg