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 CO2 was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO2-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 limbic͞paralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula͞claustrum, amygdala͞periamygdala, 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 limbic͞paralimbic 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)].

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 N2͞O2 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 amygdalar͞periamygdalar region may subserve functions of emotional representation and regulation of breathing. R egulatory physiologic processes occur continuously beyond the realm of consciousness, and only rarely do we volitionally attend to them or do they intrude and dominate conscious awareness. Feeling breathless or ''hunger for air'' is one process capable of making such an imperious intrusion. Intense breathlessness occurs in certain psychiatric states such as panic disorder (theorized to be due to a malfunction of the ''suffocation alarm'') (1), where no physiologic impairment accounts for the reaction. This fact indicates the involvement of higher brain centers, and that basic respiratory circuitry can be accessed and powerfully influenced by neural processes subserving emotion.Humans are extremely sensitive to carbon dioxide. The pathway for this effect involves pH changes (2) detected by the neurons of the ventral respiratory group. How this sensitivity leads to respiratory changes and the perception of air hunger has been explored in humans by elegant work by Banzett and colleagues (3, 4), and Gandevia and colleagues (5). Their work, including study of curarized subjects and quadriplegics, indicates that central neural processes are involved in the perception of air hunger and that peripheral afferents play a minor role.The CO 2 -sensitive neurons in the ventral respiratory group and Botzinger complexes, aligned along the ventrolateral medulla, are involved in generating respiratory rhythms. Studies in rats using anterograde and retrograde tracing of connections of the ventral respiratory group show widespread projections involving several cerebellar regions, brainstem, midbrain, hypothalamus, thalamus, amygdalohippocampal area, and i...