Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air

Abstract

There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO(2) inhalation. Comparisons were made with inhalation of a N(2)/O(2) gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing.

Figure 1

Activations and deactivations for the CO₂ FM scans compared with the O₂ FM scans displayed on the average MR brain image of the nine subjects. (a) Extensive midbrain and brainstem activations (arrowed) (x = 0; z = −8), medial frontal and large posterior cingulate deactivations (x = 0), and bilateral middle frontal gyri deactivations (z = −8). (b) Hypothalamus (arrowed), brainstem, and cerebellum activations (x = 8), and highly significant bilateral amygdala activations (arrowed) (y = −12). The positive and negative Z-score color coding is shown.

Figure 2

(a) PB versus rest. Activation of right primary motor cortex (x = 50, y = −20, z = 36, Z score = 4.6) and bilateral inferior premotor cortex (x = 54, y = −4, z = 14, Z score = 3.5; and x = −48, y = −8, z = 14, Z score = 3.4). (b) CO₂ FM versus PB. Relative deactivations in right precentral cortex (x = 50, y = −16, z = 36, Z score = −5.1) and bilateral inferior premotor cortex (x = 54, y = −8, z = 11, Z score = −4.9; and x = −52, y = −4, z = 16, Z score = −4.7). Note the colocalization of the motor-premotor effects of volitional breathing.