Neuroimaging evidence implicating cerebellum in the experience of hypercapnia and hunger for air

Abstract

Recent neuroimaging and neurological data implicate cerebellum in nonmotor sensory, cognitive, vegetative, and affective functions. The present study assessed cerebellar responses when the urge to breathe is stimulated by inhaled CO2. Ventilation changes follow arterial blood partial pressure CO2 changes sensed by the medullary ventral respiratory group (VRG) and hypothalamus, entraining changes in midbrain, pons, thalamus, limbic, paralimbic, and insular regions. Nearly all these areas are known to connect anatomically with the cerebellum. Using positron emission tomography, we measured regional brain blood flow during acute CO2-induced breathlessness in humans. Separable physiological and subjective effects (air hunger) were assessed by comparisons with various respiratory control conditions. The conjoint physiological effects of hypercapnia and the consequent air hunger produced strong bilateral, near-midline activations of the cerebellum in anterior quadrangular, central, and lingula lobules, and in many areas of posterior quadrangular, tonsil, biventer, declive, and inferior semilunar lobules. The primal emotion of air hunger, dissociated from hypercapnia, activated midline regions of the central lobule. The distributed activity across the cerebellum is similar to that for thirst, hunger, and their satiation. Four possible interpretations of cerebellar function(s) here are that: it subserves implicit intentions to access air; it provides predictive internal models about the consequences of CO2 inhalation; it modulates emotional responses; and that while some cerebellar regions monitor sensory acquisition in the VRG (CO2 concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO2, and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance. F or a century, the cerebellum was believed to be involved strictly in motor control functions (1-4). Over the last decade, a growing body of neuroimaging, neurological, and neurophysiological evidence suggests that the cerebellum has a more diverse role in brain function (5-8). ʈ Findings now implicate it in nonmotor aspects of the perception of visual motion, speed, and direction (9), auditory pitch discrimination,** visual attention (10), temporal processing (11), olfaction (12), kinesthetic processing (13), cutaneous and tactile information processing (14), language and memory tasks (8), spatial reasoning (15), and sensory and cognitive states related to thirst (16), hunger (17), affect (18), and music (19).Results indicating a role for the cerebellum in sensory processing and emotional states, including those with genesis in vegetative systems such as thirst and hunger, make it plausible that the cerebellum has a comparable role in other vegetative functions accompanied by compelling primal emotions. One such function is air hunger, and data from earlier studies of hypercapnia and air hunger note cerebellar activity (20,21).Air hunger results from increases in arterial blo...

Language of dyspnea in panic disorder

“…The factor ''sense of suffocation'' arises mainly from the stimulation of chemoreceptors [Meek and Schwartzstein, 1999] and involves the activation of the limbic/paralimbic and cerebellar regions [Banzett et al, 2000;Corfield et al, 1995;Evans et al, 2002;Liotti et al, 2001;Parson et al, 2001]. In our study, the CO 2 -induced panic attacks were linked to high factor scores for sense of suffocation, but this link disappeared after patients were subgrouped according to the similarity of CO 2 responses to their unexpected panic attacks.…”

Effects of mandibular advancement on brain activation during inspiratory loading in healthy subjects: a functional magnetic resonance imaging study

“…The cerebellum, which receives vagal inputs (24), plays an essential role in coordinating sensory aspects of loads with respiratory motor output. It has been reported that respiratory loading tasks are associated with activation of the cerebellum (11,20,27,35,46,47), as in our study. Parietal lobules are somatosensory association areas and are particularly concerned with vigilance.…”

“…Indeed, activation of these structures in response to respiratory challenges has been previously reported (5,8,11,31,35,47). The prefrontal cortex, including the middle and inferior frontal gyri, was also activated during respiratory challenge, as in previous studies (5,11,31,46). The cerebellum, which receives vagal inputs (24), plays an essential role in coordinating sensory aspects of loads with respiratory motor output.…”

A bilateral cortico-bulbar network associated with breath holding in humans, determined by functional magnetic resonance imaging

“…Interestingly, breath holding was not associated with increased activity within the cerebellum; cerebellar activity is commonly reported in human respiratory related imaging paradigms (Evans et al, 2002;McKay et al, 2003;Parsons et al, 2001) and in animals (Xu and Frazier, 2002) usually when task-related respiratory motor activity is increased.…”