No abstract

Air hunger (uncomfortable urge to breathe) is a component of dyspnea (shortness of breath). Three human H(2)(15)O positron emission tomography (PET) studies have identified activation of phylogenetically ancient structures in limbic and paralimbic regions during dyspnea. Other studies have shown activation of these structures during other sensations that alert the organism to urgent homeostatic imbalance: pain, thirst, and hunger for food. We employed blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine activation during air hunger. fMRI conferred several advantages over PET: enhanced signal-to-noise, greater spatial resolution, and lack of ionizing radiation, enabling a greater number of trials in each subject. Six healthy men and women were mechanically ventilated at 12-14 breaths/min. The primary experiment was conducted at mean end-tidal PCO(2) of 41 Torr. Moderate to severe air hunger was evoked during 42-s epochs of lower tidal volume (mean = 0.75 L). Subjects described the sensation as "like breath-hold," "urge to breathe," and "starved for air." In the baseline condition, air hunger was consistently relieved by epochs of higher tidal volume (mean = 1.47 L). A control experiment in the same subjects under a background of mild hypocapnia (mean end-tidal PCO(2) = 33 Torr) employed similar tidal volumes but did not evoke air hunger, controlling for stimulus variables not related to dyspnea. During each experiment, we maintained constant end-tidal PCO(2) and PO(2) to avoid systematic changes in global cerebral blood flow. Whole-brain images were acquired every 5 s (T2*, 56 slices, voxel resolution 3 x 3 x 3 mm). Activations associated with air hunger were determined using voxel-based interaction analysis of covariance that compared data between primary and control experiments (SPM99). We detected activations not seen in the earlier PET study using a similar air hunger stimulus (Banzett et al. 2000). Limbic and paralimbic loci activated in the present study were within anterior insula (seen in all 3 published studies of dyspnea), anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia. Elements of frontoparietal attentional networks were also identified. The consistency of anterior insular activation across subjects in this study and across published studies suggests that the insula is essential to dyspnea perception, although present data suggest that the insula acts in concert with a larger neural network.

Dyspnea (shortness of breath, breathlessness) is a major and disabling symptom of heart and lung disease. The representation of dyspnea in the cerebral cortex is unknown. In the first study designed to explore the central neural structures underlying perception of dyspnea, we evoked the perception of severe 'air hunger' in healthy subjects by restraining ventilation below spontaneous levels while holding arterial oxygen and carbon dioxide levels constant. PET revealed that air hunger activated the insular cortex. The insula is a limbic structure also activated by visceral stimuli, temperature, taste, nausea and pain. Like dyspnea, such perceptions underlie behaviors essential to homeostasis and survival.

Strong evidence suggests that the 6MWT is responsive to clinical change following cardiac rehabilitation. Intra- and intertester reliability of the 6MWT and its validity in patients undergoing cardiac rehabilitation requires further research.

SUMMARY1. Positron emission tomographic imaging of brain blood flow was used to identify areas of motor activation associated with volitional inspiration in six normal male subjects.2. Scans were performed using intravenous infusion of H2150 during voluntary targeted breathing and positive pressure passive ventilation at the same level.3. Regional increases in brain blood flow, due to active inspiration, were derived using a pixel by pixel comparison of images obtained during the voluntary and passive ventilation phases.4. Pooling data from all subjects revealed statistically significant increases in blood flow bilaterally in the primary motor cortex (left, 54%; right, 4 3%), in the right pre-motor cortex (7-6 %), in the supplementary motor area (SMA; 341 %) and in the cerebellum (4-9%).5. The site of increased neural activation in the motor cortex, associated with volitional inspiration, is consistent with an area which when stimulated, either directly during neurosurgery or transcranially with a magnetic stimulus, results in activation of the diaphragm.6. The presence of additional sites of neural activation in the pre-motor cortex and SMA appears analogous to the results of studies on voluntary limb movement. The site of the increase in the SMA was posterior to that previously reported for arm movements. These areas are believed to have a role 'upstream ' of the motor cortex in the planning and organization of movement.7. This technique provides a means of studying the volitional motor control of respiratory related tasks in man.

SUMMARY1. Positron emission tomographic (PET) imaging of regional cerebral blood flow (rCBF), using a new 3-dimensional technique of data collection, was used to identify areas of neuronal activation associated with volitional inspiration and separately with volitional expiration in five normal male subjects. A comparison of the activated areas was also undertaken to isolate regions specific for one or other active task.2. Scans were performed during intravenous infusion of H2150 under conditions of (a) volitional inspiration with passive expiration, (b) passive inspiration with volitional expiration and (c) passive inspiration with passive expiration. Four measurements in these three conditions were performed in each subject. Breathing pattern was well matched between conditions. 3. Regional increases in brain blood flow, due to increased neural activity associated with either active inspiration or active expiration, were derived using a pixel by pixel comparison of images obtained during the volitional and passive ventilation phases. Data were pooled from all runs in all subjects and were then processed to detect statistically significant (P < 005) increases in rCBF comparing active inspiration with passive inspiration and active expiration with passive expiration.4. During active inspiration significant increases in rCBF were found bilaterally in the primary motor cortex dorsally just lateral to the vertex, in the supplementary motor area, in the right lateral pre-motor cortex and in the left ventrolateral thalamus.5. In active expiration significant increases in rCBF were found in the right and left primary motor cortices dorsally just lateral to the vertex, the right and left primary motor cortices more ventrolaterally, the supplementary motor area, the right lateral pre-motor cortex, the ventrolateral thalamus bilaterally, and the cerebellum.6. Using this modified and more sensitive PET technique, these findings essentially replicate those for volitional inspiration obtained in a previous study. 7. The technique used has been successful in demonstrating the regions of the brain involved in the generation of volitional breathing, and probably in the volitional modulation of automatic breathing patterns such as would be required for the production of speech.

1. Positron emission tomography (PET) was used to identify the neuroanatomical correlates underlying 'central command' during imagination of exercise under hypnosis, in order to uncouple central command from peripheral feedback.2. Three cognitive conditions were used: condition I, imagination of freewheeling downhill on a bicycle (no change in heart rate, HR, or ventilation, V I ): condition II, imagination of exercise, cycling uphill (increased HR by 12 % and V I by 30 % of the actual exercise response): condition III, volitionally driven hyperventilation to match that achieved in condition II (no change in HR).3. Subtraction methodology created contrast A (II minus I) highlighting cerebral areas involved in the imagination of exercise and contrast B (III minus I) highlighting areas activated in the direct volitional control of breathing (n = 4 for both; 8 scans per subject). End-tidal P CO 2 (P ET,CO 2 ) was held constant throughout PET scanning.4. In contrast A, significant activations were seen in the right dorso-lateral prefrontal cortex, supplementary motor areas (SMA), the right premotor area (PMA), superolateral sensorimotor areas, thalamus, and bilaterally in the cerebellum. In contrast B, significant activations were present in the SMA and in lateral sensorimotor cortical areas. The SMA/PMA, dorso-lateral prefrontal cortex and the cerebellum are concerned with volitional/motor control, including that of the respiratory muscles.5. The neuroanatomical areas activated suggest that a significant component of the respiratory response to 'exercise', in the absence of both movement feedback and an increase in CO 2 production, can be generated by what appears to be a behavioural response.

We have defined areas in the brain activated during speaking, utilizing positron emission tomography. Six normal subjects continuously repeated the phrase "Buy Bobby a poppy" (requiring minimal language processing) in four ways: A) spoken aloud, B) mouthed silently, C) without articulation, and D) thought silently. Statistical comparison of images from conditions A with C and B with D highlighted areas associated with articulation alone, because control of breathing for speech was controlled for; we found bilateral activations in sensorimotor cortex and cerebellum with right-sided activation in the thalamus/caudate nucleus. Contrasting images from conditions A with B and C with D highlighted areas associated with the control of breathing for speech, vocalization, and hearing, because articulation was controlled for; we found bilateral activations in sensorimotor and motor cortex, close to but distinct from the activations in the preceding contrast, together with activations in thalamus, cerebellum, and supplementary motor area. In neither subtraction was there activation in Broca's area. These results emphasize the bilaterality of the cerebral control of "speaking" without language processing.