Arousal from sleep is an important component of the protective responses to physiological challenges during sleep, helping to protect the infant from potentially dangerous situations, even sudden death. Failure of arousal mechanisms may contribute to the etiology of SIDS. In human infants, arousals may be elicited by stimuli such as hypercapnia, hypoxia, laryngeal stimulation, changes in blood pressure, sound, or touch. It is clear that there are several 'levels' of arousal including subcortical (spinal and brainstem) and cortical (EEG) arousals. Information about the patterns and characteristics of spontaneous arousals in infants, however, is limited. Indeed, the criteria for identifying arousals in infants remain controversial. Importantly, the relative importance of the different levels of arousal for survival is unknown. Subcortical arousals associated with changes in breathing, blood pressure, heart rate, and heart rate variability, may be particularly important in infants. Other infant behaviors that are associated with changes in autonomic activity, such as feeding, may have important influences on arousal mechanisms. Our knowledge about arousals in infants has been largely derived from experiments where infants were exposed to external stimuli and where the observed response was a full 'awakening'. Much less is known about spontaneous arousals which do not result in a full awakening. Finally, there are no standards for the evaluation of spontaneous arousals in infants and little is known about their development. As part of the Collaborative Home Infant Monitoring Evaluation (CHIME) study, overnight polysomnograms were performed on 634 infants. These infants were divided into four groups for analysis including healthy term infants, infants suffering from at least one ALTE, siblings of SIDS victims, and premature infants. In addition, important demographic data were collected including maternal age, cigarette smoking, and alcohol use. The large CHIME dataset contains a wealth of information about sleep and arousal in infants at risk for SIDS, but has not been analyzed with regard to the frequency, duration, and level of arousals, or the relationship of arousals with autonomic function or with risk factors for SIDS, such as sustaining an ALTE or prematurity. The purpose of this proposal is to systematically examine spontaneous arousals in this large group of CHIME sleep recordings. We will evaluate the efficacy of an automated arousal analysis that will help standardize definitions. We will also make comparisons between the characteristics of arousals in healthy full term infants and those at risk for SIDS, including full term ALTE and premature infants, including the effects of maternal cigarette smoking. We will also focus on shifts in autonomic activity during different levels (subcortical and cortical) of arousals using sophisticated measures of heart rate variability. Finally, we will examine the relationships among the level of arousal, post-conceptional age, sleep state, and other infant behaviors such as feeding that are also associated with changes in autonomic activity.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD045653-01
Application #
6710789
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Willinger, Marian
Project Start
2004-01-15
Project End
2006-12-31
Budget Start
2004-01-15
Budget End
2004-12-31
Support Year
1
Fiscal Year
2004
Total Cost
$422,009
Indirect Cost
Name
Dartmouth College
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Myers, M M; Grieve, P G; Izraelit, A et al. (2012) Developmental profiles of infant EEG: overlap with transient cortical circuits. Clin Neurophysiol 123:1502-11
Brown, J W; Sirlin, E A; Benoit, A M et al. (2008) Activation of 5-HT1A receptors in medullary raphe disrupts sleep and decreases shivering during cooling in the conscious piglet. Am J Physiol Regul Integr Comp Physiol 294:R884-94
Hoffman, J M; Brown, J W; Sirlin, E A et al. (2007) Activation of 5-HT1A receptors in the paragigantocellularis lateralis decreases shivering during cooling in the conscious piglet. Am J Physiol Regul Integr Comp Physiol 293:R518-27
Darnall, Robert A; Harris, Michael B; Gill, W Hugh et al. (2005) Inhibition of serotonergic neurons in the nucleus paragigantocellularis lateralis fragments sleep and decreases rapid eye movement sleep in the piglet: implications for sudden infant death syndrome. J Neurosci 25:8322-32