Brain responses associated with consciousness of breathlessness (air hunger)

Abstract

Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO(2) was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO(2-) was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic/paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala/periamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic/paralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].

Figure 1

PET activations and deactivations for the CO₂FM vs. CO₂MP conditional contrast of displayed on the average MRI brain image of the nine subjects. a shows activations in the anterior cingulate region (x = 0), bilaterally in the middle temporal gyrus (y = −2), and in the right midbrain (y = −28). Deactivations are evident in the left caudate nucleus (y = −2), the medial anterior cingulum (x = 0), and the left pulvinar and left inferior parietal lobule (y = −28). b shows activations in the left lingual gyrus (x = −18) and right anterior cingulate, posterior thalamus, and lingual gyrus (x = 18). Deactivations can be observed in the left medial frontal gyrus, bilaterally in the cerebellum, and in the right lentiform nucleus (x = 18).

Figure 2

Positive and negative correlations of breathlessness scores with rCBF during CO₂ FM and CO₂ MP scans displayed on the average MRI brain image. Significant correlations are evident in the lingual gyrus, anteriorly and rostrally in the cingulate gyrus (x = −4), and in the sublenticular area and right temporal gyrus (z = −6). The color coding of the correlation coefficients is shown.

Figure 3

Locations in Talairach coordinates of the activations in the anterior cingulate cortex in published studies of hunger for air, thirst, hunger, micturition pain, and REM sleep (automatic rendering from brainmap search and view software, University of Texas Health Science Center, San Antonio). Air Hunger: Brannan and coworkers (9) CO₂FM inhalation vs. CO₂MP inhalation (red square); breathlessness correlation (red circle). Thirst: Denton et al. (25) maximum thirst vs. rest (green square); Denton et al. (13) plasma [Na⁺] correlation (green circle). Hunger: Tataranni et al. (30) 36-h fast vs. satiation (orange square). Micturition: Blok et al. (37, 50); a series of comparisons involving micturition, withholding urine, and empty bladder (magenta). Pain Rainville et al. (34); a series of comparisons involving painful hot vs. warm or neutral (blue); other comparisons (cyan or pink) involving painful heat vs. warm nonpainful or neutral (, –55). Sleep: Maquet et al. (41) REM sleep (black star).