The Cerebral Cost of Breathing: An fMRI Case-Study in Congenital Central Hypoventilation Syndrome

<div><p>Certain motor activities - like walking or breathing - present the interesting property of proceeding either automatically or under voluntary control. In the case of breathing, brainstem structures located in the medulla are in charge of the automatic mode, whereas cortico-subcortical brain networks - including various frontal lobe areas - subtend the voluntary mode. We speculated that the involvement of cortical activity during voluntary breathing could impact both on the “resting state” pattern of cortical-subcortical connectivity, and on the recruitment of executive functions mediated by the frontal lobe. In order to test this prediction we explored a patient suffering from central congenital hypoventilation syndrome (CCHS), a very rare developmental condition secondary to brainstem dysfunction. Typically, CCHS patients demonstrate efficient cortically-controlled breathing while awake, but require mechanically-assisted ventilation during sleep to overcome the inability of brainstem structures to mediate automatic breathing. We used simultaneous EEG-fMRI recordings to compare patterns of brain activity between these two types of ventilation during wakefulness. As compared with spontaneous breathing (SB), mechanical ventilation (MV) restored the default mode network (DMN) associated with self-consciousness, mind-wandering, creativity and introspection in healthy subjects. SB on the other hand resulted in a specific increase of functional connectivity between brainstem and frontal lobe. Behaviorally, the patient was more efficient in cognitive tasks requiring executive control during MV than during SB, in agreement with her subjective reports in everyday life. Taken together our results provide insight into the cognitive and neural costs of spontaneous breathing in one CCHS patient, and suggest that MV during waking periods may free up frontal lobe resources, and make them available for cognitive recruitment. More generally, this study reveals how the active maintenance of cortical control over a continuous motor activity impacts on brain functioning and cognition.</p></div

Restoration of DMN under mechanical ventilation.

<p>(A). Comparison of BOLD signal between MV and SB revealed a specific increase of activation in the default-mode network associated in awake controls in introspection and self-consciousness. No significant result was observed in the opposite contrast. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107850#pone-0107850-t001" target="_blank">Table 1</a> for detailed fMRI results. (B&C). Functional connectivity assessed with a hypothesis-driven approach revealed a larger correlation with precuneus activity in posterior mesial areas during MV than during SB (B), and a larger correlation between brainstem activity and a large anterior cortico-subcortical network during SB than during MV (C). This large network resembles the executive attention network.</p

Functional MR connectivity assessed with an ICA method.

<p>(A).Default mode network (DMN): bilateral medial prefrontal and anterior cingulate cortices (1), bilateral precuneus (2), bilateral superior parietal cortices (3). (B).Mean values ± standard deviation of DMN integrations for the mechanical (MV) and the spontaneous (SB) breathing blocks of resting state. The asterisk indicates a significant difference between conditions. (C). Sensorimotor network (SMN): bilateral supplementary motor area (1) and bilateral sensorimotor cortices (2). (D).Mean values ± standard deviation of SMN integrations for the mechanical (MV) and the spontaneous (SB) breathing blocks of resting state. NS  =  non-significant difference between conditions; AU  =  arbitrary unit.</p

Stability of wakefulness under MV and SB indexed by EEG.

<p>(A). Scalp voltage topographies of alpha power (up) and theta (bottom) averaged across the 4 EEG-fMRI sessions reveal a typical pattern of wakefulness characterized by a high posterior alpha power and a low anterior mid-frontal power. (B). Dynamics of the (posterior alpha power)/(mid-frontal theta power) ration is plotted across time for the 4 EEG-fMRI sessions. This index of wakefulness was stable across the 4 sessions, and confirmed a stable level of wakefulness all along the fMRI experiments, with no difference between SB and MV.</p

Synthesis of fMRI results.

<p>Synthesis of fMRI results.</p