Neuroanatomic deficits in congenital central hypoventilation syndrome

Abstract

Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation.

Associations Between Variants Near a Monoaminergic Pathways Gene (PHOX2B) and Amygdala Reactivity: A Genome-Wide Functional Imaging Study

“…The current result is in line with these earlier candidate gene studies, as it demonstrates how genetic variation in a regulatory step of monoaminergic signaling that affects cerebral monoaminergic tone subsequently relates to amygdala neuronal signaling. Moreover, volumetric effects of variants linked to the MAOA gene and the serotonin transporter gene on amygdala structures are consistent with emerging evidence that indicates some structural damage in amygdala and interconnected limbic structures in CCHS patients (Kumar et al, 2006;Kumar et al, 2005). These results indicate that genetic variation in monoaminergic signaling pathways affects not only amygdala neural activity, but also structural integrity.…”

Age‐related regional brain T2‐relaxation changes in healthy adults

“…T2-relaxometry procedures provide a noninvasive means to evaluate even subtle tissue changes not detectable on visual examination (18,23,24). The procedure measures free water content (9), and T2-relaxation values are indicative of the distribution of free tissue water and interactions with the neighboring tissue structural environment (25), in the absence of diamagnetic and paramagnetic substances.…”

Aberrant Central Nervous System Responses to the Valsalva Maneuver in Heart Failure

“…Several of these brain areas that showed impaired signals, especially insular, cerebellar, and hippocampal regions, have previously been shown to exhibit gray matter loss in HF 3 and are regions associated with reduced gray matter volume or neural injury in other patient populations with breathing disorders. 26,27 The muted heart rate patterns might be expected to result from less responsive central autonomic site activity. Unexpectedly, many of the areas associated with ANS control showed exaggerated responses in HF relative to the reactions in control subjects.…”