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 CO(2). Ventilation changes follow arterial blood partial pressure CO(2) 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 CO(2)-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 CO(2) inhalation; it modulates emotional responses; and that while some cerebellar regions monitor sensory acquisition in the VRG (CO(2) concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO(2), and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance.

Figure 1

PET activity (red-yellow) shown on the average MR brain of the nine subjects where breathing the CO₂ mixture in a FM (CO₂ FM) is compared (a–c) and (f) to breathing a nitrogen/oxygen mixture in a FM (O₂ FM) or (d and e) to voluntary PB of room air (hyperventilation). (a) Activation (upper arrow) in quadrangular lobule (V, VI) and pyramis (vermis) (lower arrow) (coronal section y = −48). (b) Activation in bilateral biventer lobule (VIIIB) (transverse section z = −44). (c) Activation in bilateral declive (vermis) (VI) (coronal section y = −66). (d) Bilateral activation in quadrangular lobule (coronal section y = −52). (e) Activation in biventer lobule (transverse section z = −46). (f) Activation in central lobule (upper arrow) and tonsil (lower arrow) (sagittal section x = −14). The color coding of Z scores is shown in Fig. 2.

Figure 2

PET deactivations (blue-green) displayed on the average MR brain where breathing the CO₂ mixture in a FM (CO₂ FM) is compared with breathing a nitrogen/oxygen mixture in a FM (O₂ FM). Two foci in gracile lobule (VIIB) (coronal section y = −76) are shown.

Figure 3

PET activity displayed on the average MR brain where breathing the CO₂ mixture in a FM (CO₂ FM) is compared with the image of breathing CO₂ with a MP (CO₂ MP). (a) Activation in central lobule (III) (sagittal section x = −4). (b) Deactivation bilaterally in inferior semilunar (Crus II) (upper arrow) and gracile lobule (VIIB) (lower arrow). The color coding of Z scores is shown in Fig. 2.

Figure 4

The correlation of changes in cerebellar rCBF and breathlessness score. Activation in central lobule (III) (transverse section z = −28 mm) is shown.