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 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...

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

“…Limbic areas, including the parahippocampal gyrus, insula, and cingulate gyrus, participate in emotive and visceral sensorimotor functions. 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).…”

“…This structure is also related to the control of certain autonomic (5), and emotion related to a need for air (11). Indeed, it has been demonstrated that the cingulate cortex has a complex and indirect relationship to central networks that control respiration (8,15). Therefore, we should expect that deactivation of the cingulate cortex might be observed in association with a relief from breathing difficulty by mandibular advancement.…”

“…It has been shown that respiratory loading is associated with the activation of basal ganglia (5,8,11,20,27,31,35,47). Limbic areas, including the parahippocampal gyrus, insula, and cingulate gyrus, participate in emotive and visceral sensorimotor functions.…”

Beyond the usual suspects: a cholinergic route for panic attacks

“…The inhalation of CO 2 in man activates a pathway of responses that originate in the ventral medulla 21,43,44 and extend to the pons, midbrain, limbic and paralimbic areas, the parahippocampal and fusiform gyrus, and the anterior insula. 43,44 This physiological response network connects an element of basic respiratory control to the affective states of air hunger and fear that are promoted when respiratory disturbance becomes a salient element of consciousness. 43 However, functional imaging data show that activation of the limbic and cortical regions in man also depend upon subjective sensations of respiratory constraint and air hunger, as obtainable by the application to volunteers of a facemask for breathing.…”

“…43,44 This physiological response network connects an element of basic respiratory control to the affective states of air hunger and fear that are promoted when respiratory disturbance becomes a salient element of consciousness. 43 However, functional imaging data show that activation of the limbic and cortical regions in man also depend upon subjective sensations of respiratory constraint and air hunger, as obtainable by the application to volunteers of a facemask for breathing. 43,44 There thus seem to be partially independent pathways that lead to limbic activation-and the corresponding emotions of anxiety or fear-in response to objective and perceived suffocation.…”