Electroencephalographic evidence for pre-motor cortex activation during inspiratory loading in humans

Abstract

Faced with mechanical inspiratory loading, awake animals and anaesthetized humans develop alveolar hypoventilation, whereas awake humans do defend ventilation. This points to a suprapontine compensatory mechanism instead of or in addition to the 'traditional' brainstem respiratory regulation. This study assesses the role of the cortical pre-motor representation of inspiratory muscles in this behaviour. Ten healthy subjects (age 19-34 years, three men) were studied during quiet breathing, CO2-stimulated breathing, inspiratory resistive loading, inspiratory threshold loading, and during self-paced voluntary sniffs. Pre-triggered ensemble averaging of Cz EEG epochs starting 2.5 s before the onset of inspiration was used to look for pre-motor activity. Pre-motor potentials were present during voluntary sniffs in all subjects (average latency (+/-s.d.): 1325 +/- 521 ms), but also during inspiratory threshold loading (1427 +/- 537 ms) and during inspiratory resistive loading (1109 +/- 465 ms). Pre-motor potentials were systematically followed by motor potentials during inspiratory loading. Pre-motor potentials were lacking during quiet breathing (except in one case) and during CO2-stimulated breathing (except in two cases). The same pattern was observed during repeated experiments at an interval of several weeks in a subset of three subjects. The behavioural component of inspiratory loading compensation in awake humans could thus depend on higher cortical motor areas. Demonstrating a similar role of the cerebral cortex in the compensation of disease-related inspiratory loads (e.g. asthma attacks) would have important pathophysiological implications: it could for example contribute to explain why sleep is both altered and deleterious in such situations.

Figures

Figure 1. Representative example of the pre-inspiratory EEG activity recorded in one subject during quiet breathing with a low dead space pneumotachograph, inspiratory threshold loading, inspiratory resistive breathing, quiet breathing with a low resistance pneumotachograph, CO2 breathing, and self-paced sniffs

Llow dead space pneumotachograph (control 1; top, left), inspiratory threshold loading (ITL; top, middle), inspiratory resistive breathing (IRL; top, right), quiet breathing with a low-resistance pneumotachograph (control 2; bottom, left), CO2 breathing (bottom, middle) and self-paced sniffs (bottom, right). The vertical arrows indicate the triggering point. The recording during CO2 breathing shown here was obtained using a preamplifier connected to the scalp electrode, whereas this was not the case for the other signals. Cz-A+, vertex EEG derivation; ScalEMG, root mean square scalene muscle EMG; Press, mouth or nasal pressure. The EEG positivity at the leftmost part of the ITL trace (and to a lesser extent of the IRL trace) corresponds to the end of the cortical activity related to the previous cycle.

Figure 2. Ensemble averaging of the inspiratory pre-motor activities recorded in all the subjects, under the control 1 condition, self-paced sniffs and mechanical loading

The vertical arrows indicate the triggering point. In the ‘sniffs’ panel, two EEG traces can be seen. The top one was obtained from all the subjects; it shows an initial positivity (also seen, to a lesser extent, on the IRL trace) that corresponds to the end of the cortical activity related to the previous cycle. The second EEG trace, that does not feature the initial positivity, corresponds to the ensemble averaging of the data gathered for the six subjects who performed low frequency sniffs.

Figure 3. Proportion of subjects exhibiting pre-motor potentials in the various study conditions

Control 1, quiet breathing with a low dead space pneumotachograph (see Methods); control 2, quiet breathing with a low resistance pneumotachograph (see Methods); FI,CO2 7%, 7% inspired fraction of CO2. *Significant difference versus the control 1 condition (P < 0.05).

Figure 4. Proportion of subjects exhibiting motor potentials in the various study conditions

Control 1, quiet breathing with a low dead space pneumotachograph (see Methods); control 2, quiet breathing with a low resistance pneumotachograph (see Methods); FI,CO2 7%, 7% inspired fraction of CO2. *Significant difference versus the control 1 condition (P < 0.05).

Figure 5. Ensemble averaging of the inspiratory pre-motor activities recorded in one subject on two separate occasions (top and bottom) during self-paced sniffs (left) and ITL (right)

The vertical arrows indicate the triggering point. The EEG positivity at the leftmost part of the ITL traces corresponds to the end of the cortical activity related to the previous breath (magnified on the day 2 recording because of an increased respiratory frequency reducing the inter-breath period). *Denotes the use of a preamplifier shown to eliminate cable movement artefacts (see Methods).