FMRI responses to hyperoxia in congenital central hypoventilation syndrome.

Pediatr Res

School of Nursing, Department of Neurobiology, University of California, Los Angeles, Los Angeles, California 90095, and Childrens Hospital, Los Angeles, California 90027, USA.

Published: April 2005

Congenital Central Hypoventilation Syndrome (CCHS) patients show partial retention of peripheral chemoreception despite impaired ventilatory responses to CO2 and hypoxia. The condition allows examination of central responses to hyperoxia, which minimizes afferent traffic from peripheral chemoreceptors. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals over the brain during a baseline and subsequent 2-min hyperoxia (100% O2) period in 14 CCHS and 15 control subjects. After partitioning gray matter and correcting for global effects, the images were analyzed using volume-of-interest time trends followed by repeated-measures ANOVA and conventional cluster analyses. Respiratory rates initially (first 20 s) fell in CCHS, but rose in control subjects; CCHS heart rate increased in the first minute, and then decreased in the second minute, as in controls, but with muted rise and extent of decline. Multiple sites within the cerebellum, midbrain, and pons responded similarly to the challenge in both groups. Response patterns differed early in the right amygdala, paralleling initial respiratory pattern deficits, and late in the right insula, concomitant with cardiac rate differences. Signals also differed between groups in the medial and anterior cingulate, hippocampus, head of caudate, and lentiform nuclei, as well as pontine and midbrain structures and regions within the superior temporal and inferior frontal cortical gyri. The findings emphasize that structures that can alter respiratory timing, such as the amygdala, and modulate sympathetic outflow, such as the right insula, are deficient in CCHS. Medullary and pontine areas targeted by PHOX2B expression are also affected.

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http://dx.doi.org/10.1203/01.PDR.0000155763.93819.46DOI Listing

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