Hippocampal volume reduction in congenital central hypoventilation syndrome.

Children with congenital central hypoventilation syndrome (CCHS), a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO(2) sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI) scans, with impaired responses in specific hippocampal regions, suggesting localized injury.We assessed total volume and regional variation in hippocampal surface morphology to identify areas affected in the syndrome. We studied 18 CCHS (mean age+/-std: 15.1+/-2.2 years; 8 female) and 32 healthy control (age 15.2+/-2.4 years; 14 female) children, and traced hippocampi on 1 mm(3) resolution T1-weighted scans, collected with a 3.0 Tesla MRI scanner. Regional hippocampal volume variations, adjusted for cranial volume, were compared between groups based on t-tests of surface distances to the structure midline, with correction for multiple comparisons. Significant tissue losses emerged in CCHS patients on the left side, with a trend for loss on the right; however, most areas affected on the left also showed equivalent right-sided volume reductions. Reduced regional volumes appeared in the left rostral hippocampus, bilateral areas in mid and mid-to-caudal regions, and a dorsal-caudal region, adjacent to the fimbria.The volume losses may result from hypoxic exposure following hypoventilation during sleep-disordered breathing, or from developmental or vascular consequences of genetic mutations in the syndrome. The sites of change overlap regions of abnormal functional responses to respiratory and autonomic challenges. Affected hippocampal areas have roles associated with memory, mood, and indirectly, autonomic regulation; impairments in these behavioral and physiological functions appear in CCHS.

Mother-infant bedsharing is associated with an increase in infant heart rate.

OBJECTIVES: We hypothesized that mother-infant bed sharing, compared to solitary sleeping, would be associated with higher infant heart rates. The objective was to compare infant heart rates between the 2 environments and, secondarily, to test for relationships between heart rate and other, previously reported, differences in the same infants. DESIGN: Heart rate was measured in 15 infants over a bed-sharing night and a solitary-sleeping night. Eight of the 15 infants routinely bed shared with the mother at home; the other 7 routinely slept in a room alone. SETTING: The Sleep Disorders Center, University of California, Irvine Medical Center. PARTICIPANTS: Fifteen mother-infant pairs who met criteria for routinely bed sharing or sleeping solitarily. All were healthy, and infants were more than 38 weeks gestation at birth and 11 to 15 weeks old at the time of the study. INTERVENTIONS: None. RESULTS: Analysis of variance indicated that, irrespective of routine sleeping condition, heart rate was lower during solitary sleeping than during bed sharing in all sleep stages. Significant regressions were found with infant temperature. Heart-rate variability was higher during solitary sleeping than during bed sharing (both routine groups) in stages 1 and 2 and rapid eye movement sleep, but only stages 1 and 2 sleep effects were independent of basal heart rate. CONCLUSIONS: Infant heart rate is affected by the mother's presence in the sleep environment. The increase in sympathetic activity in stages 3 and 4 and rapid eye movement sleep might be partly explained by differences in thermoregulation between bed-sharing and solitary-sleeping environments. These results support the notion that sensory differences between bed-sharing and solitary-sleeping environments account for some of the physiologic differences between infant sleep in the 2 sleeping conditions.

Late-developing rostral ventrolateral medullary surface responses to cardiovascular challenges during sleep.

Pressor and depressor manipulations are usually followed by compensatory autonomic, respiratory, somatomotor or arousal responses that limit the extent of blood pressure change. Of neural sites participating in blood pressure control, the rostral ventrolateral medullary surface (RVLMS) contributes significantly, and exhibits rapid-onset overall activity declines and increases to pressor and depressor challenges, respectively. In addition, longer-latency physiological responses develop that further compensate for the homeostatic challenge; some of these later influences are associated with arousal. Late-developing RVLMS activity changes accompanying physiologic responses that normalize a cardiovascular manipulation may provide insights into compensatory neural mechanisms during sleep following sustained or extreme blood pressure changes. We used intrinsic optical imaging procedures in seven unanesthetized adult cats to examine RVLMS and control site responses to pressor and depressor challenges during sleep that resulted in somatomotor, respiratory, heart rate or electroencephalographic indications of late-developing (post-baroreflex) compensatory responses. Although initial RVLMS responses differed in direction between pressor and depressor challenges, neural activity increased later in both manipulations, coincident with overt physiological manifestations indicative of compensatory responses, including arousal. Arousal occurred in 44% of blood pressure challenges. Comparable late-developing neural activity increases were not apparent in control sites. Latencies of late RVLMS responses during rapid eye movement sleep were significantly longer than in quiet sleep for pressor challenges. The pattern of the late RVLMS responses was not dependent on arousal, and suggests that the RVLMS participates in both the early baroreflex response and the late-developing compensatory actions.

Structural mechanisms underlying autonomic reactions in pediatric arousal.

Arousal provides an essential means to restore homeostasis following a system perturbation during a quiescent state. The classic definition of 'arousal' includes a constellation of cardiovascular, respiratory and somatic muscle characteristics, together with activation of the electrocorticogram (ECoG). At least two ascending activating systems, a ventral cholinergic and a serotonergic ascending system, both interacting with other regional neurotransmitter processes, contribute to electrocortical activation, with separate behaviors mediated by each system. A number of 'arousal' processes essential for survival operate at local levels, and interact with the systems that mediate cortical activation. These processes include cerebellar compensatory mechanisms which respond to extreme cardiovascular challenges, and limbic structures which respond to hypoxia or hypercarbia and the resultant dyspnea. The local processes show exceptional cortical arousing properties upon recruitment of some structures, such as the amygdala, which has major projections to ascending arousal systems. Components of arousal can emerge without ECoG activation and can be mediated at local levels which interact with ascending systems.