Abstract â–¡ 9

Physiological characteristics of SIDS victims prior to death, together with cardiac and respiratory patterns in some victims during the event, suggest that a failure to maintain perfusion, or an inability of respiratory and other somatic systems to adequately compensate for cardiovascular dysfunction underlies the fatal sequence. A first step in determining the mechanisms of failure is to describe the neural structures involved in mediating compensatory responses to alterations in blood pressure. Apnea or depression of the respiratory musculature accompanies transient elevations in blood pressure, while substantially enhanced respiratory and somatic efforts assist restoration of perfusion with a loss of blood pressure. The objective of these studies was to determine the brain areas which activate and integrate appropriate responses to blood pressure and breathing challenges.

Normal adults and children, as well as infants with congenital central hypoventilation syndrome (CCHS; ventilator-dependent only during sleep; no Hirschsprung's Disease) were examined with functional magnetic resonance imaging (fMRI) techniques while undergoing ventilatory and blood pressure challenges. Blood pressure challenges included cold pressor application to the forehead or hand, and Valsalva maneuvers. Ventilatory challenges included mild hypoxia (15% O2) and hypercapnia (5% CO2). A series of 20 image slices (20 repetitions, Echo Planar technique) through the entire brain was collected during a baseline period and during each challenge; images taken under experimental conditions were compared to images obtained under baseline conditions and subjected to multiple paired t-tests with Bonferroni correction (p<0.01) using MedX software. The extents of changes were pseudo-colored and overlaid on the first image in the series.

Blood pressure and ventilatory challenges elicited widespread activation in several rostral brain sites as well as brain stem and cerebellar areas. Blood pressure increases were particularly effective in activating hippocampal, insular, and medial frontal areas, as well as deep cerebellar nuclei in controls. An unexpected finding was the responses to blood pressure elevation were frequently unilateral. Areas within the midline and lateral deep cerebellar nuclei, as well as portions of the midbrain did not respond to hypercapnia in substantial portion of CCHS patients; responses to hypoxia were diminished in a smaller proportion of cases.

The findings indicate a major role or cerebellar structures in mediating appropriate responses to blood pressure and ventilatory challenges. We speculate that this brain structure, classically associated with integration of motor functions, also serves compensatory and integrative roles for the somatic respiratory and autonomic motor systems.

Supported by HD36228 and HL-22418