Areas of the brain concerned with ventilatory load compensation in awake man

Abstract

There is broad agreement that the awake human ventilatory response to a moderate inspiratory load consists of a prolongation of inspiratory time (T(I)) with a maintenance of tidal volume (V(T)) and end-tidal P(C)(O(2)) (P(ET,C)(O(2))), the response being severely blunted in sleep. There is no agreement on the mechanisms underlying this ventilatory response. Six naive healthy males (aged 39-44) were studied supine with their heads in a positron emission tomography (PET) scanner to allow relative regional cerebral blood flow (rCBF) to be measured with H(2)(15)O given intravenously. A linearised resistive load (24 cmH(2)O (l s(-1))(-1)) could be added to the inspiratory limb of a breathing valve inserted into a tightly fitting facemask; inspiratory flow was measured with a pneumotachograph. The load was applied, without alerting the subject, when the radioactivity first reached the head. Six scans were performed with and without the load, in each subject. Relative rCBF contrasts between the loaded and unloaded breathing states showed significant activations in inferior parietal cortex, prefrontal cortex, midbrain, basal ganglia and multiple cerebellar sites. No activations were found in the primary sensorimotor cortex. The findings suggest that there is a pattern of motor behavioural response to the uncomfortable sensation that inspiration is impeded. This results in a prolongation of T(I), the maintenance of V(T) and a reduction in the degree of discomfort, presumably because of the reduction of mean negative pressure in the airways.

Figure 1. Typical response to the addition of a 24 cmH₂O (l s⁻¹)⁻¹ inspiratory resistive load

V̇, inspiratory flow; V_T inspiratory tidal volume; P_mask, pressure in face mask; and P_ET,CO2, signal from the nose. The period over which the PET scan was taken is indicated. The increase in inspiratory time in response to the load is more clearly seen in the expanded section at the top of the figure. Note the immediate overshoot in V_T following the removal of the load.

Figure 2. Means ± s.d. for T_I and V_T across subjects for the two breaths before the application of the load (pre), the first two breaths after the application of the load (on), the last two breaths before the removal of the load (on), and the first two breaths after removal of the load (off)

Significant differences (using Fisher's LSD) are shown as *P < 0.05 and **P < 0.01; the first two breaths after load application are not significantly different from the preceding breath. Results derived from ANOVA.

Figure 3. Indicated respiratory variables averaged across runs for each subject for the 90 s period at the start of the scan

Inspiratory time (T_I), expiratory time (T_E), tidal volume (V_T), ventilation (V_I) end-tidal P_CO2 (P_ET,CO2) and the peak inspiratory mask pressure (P_mask). The mean values are shown with different symbols for each subject and are plotted in the ‘no-load’ condition (U) on the Y-axis and the ‘loaded’ condition (L) on the X-axis; the ‘line of identity’ is shown. The mean value across all subjects for each variable is shown as a circle with a cross. The P value (paired t test) is shown above each graph and compares unloaded with loaded breathing.

Figure 4. Group results of relative rCBF increases associated with inspiratory resistive loading are shown as through projections onto representations of stereotactic space in sagittal view (A), coronal view from behind (B) and transverse view from above (C), anterior to the right

The areas of activation reaching statistical significance (P < 0.0001; T > 3.93) without correction for multiple comparisons are shown. Increasing significance is shown by an arbitrary scale ranging from light gray to black.

Figure 5. Group results of relative rCBF increases associated with inspiratory resistive loading, shown on a surface-rendered representative MRI of the brain (Evans et al. 1993)

The rendering process follows the true brain surface and shows activations up to 3 cm below this surface, The colour scale indicates the statistical level (T) of the activations. Sagittal section in mid-line: A, left hemisphere showing both cerebella and midbrain activations; B, right hemisphere, showing both cerebella and midbrain activations. C, posterior view showing activations in the cerebellum and both parietal cortices; D, anterior view showing activation in the right parietal cortex. E, right lateral brain surface showing activations in the cerebellum, inferolateral precentral gyrus and inferior parietal lobule; F, left brain surface showing activations in the inferolateral precentral gyrus and the parietal supramarginal gyrus. G, inferior surface, right anterior, showing widespread activations in the cerebellum and probably thalamus; H, superior surface, right anterior, showing activations in the right and left parietal cortex and the right inferolateral precentral gyrus.

Figure 6. Group results of relative rCBF increases within the midbrain associated with inspiratory resistive loading are shown on sagittal and coronal sections of a T1-weighted magnetic resonance image of a representative brain (Evans et al. 1993)

The cross hairs are centred on the most significantly activated voxel; X, Y and Z are the standard MNI coordinates in stereotatic space (Evans et al. 1993). The images are displayed (P < 0.01) after correction for multiple comparisons. A, mid-brain activation as in Table 1; B, activation near aqueduct of Sylvius; C, activation close to red nucleus, extending into the right thalamus.