States of peripheral autonomic arousal accompany emotional behaviour, physical exercise and cognitive effort, and their central representation may influence decision making and the regulation of social and emotional behaviours. However, the cerebral functional neuroanatomy representing and mediating peripheral autonomic responses in humans is poorly understood. Six healthy volunteer subjects underwent H215O positron emission tomography (PET) scanning while performing isometric exercise and mental arithmetic stressor tasks, and during corresponding control tasks. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored during scanning. Data were analysed using statistical parametric mapping (SPM99). Conjunction analyses were used to determine significant changes in regional cerebral blood flow (rCBF) during states of cardiovascular arousal common to both exercise and mental stressor tasks. Exercise and mental stressor tasks, relative to their control tasks, were associated with significantly (P < 0.001) increased MAP and HR. Significant common activations (increased rCBF) were observed in cerebellar vermis, brainstem and right anterior cingulate. In both exercise and mental stress tasks, increased rCBF in cerebellar vermis, right anterior cingulate and right insula covaried with MAP; rCBF in pons, cerebellum and right insula covaried with HR. Cardiovascular arousal in both categorical and covariance analyses was associated with decreased rCBF in prefrontal and medial temporal regions. Neural responses in discrete brain regions accompany peripheral cardiovascular arousal. We provide evidence for the involvement of areas previously implicated in cognitive and emotional behaviours in the representation of peripheral autonomic states, consistent with a functional organization that produces integrated cardiovascular response patterns in the service of volitional and emotional behaviours.

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.

To investigate the functional neuroanatomy of voluntary respiratory control, blood O2 level-dependent functional magnetic resonance imaging was performed in six healthy right-handed individuals during voluntary hyperpnea. Functional images of the whole brain were acquired during 30-s periods of spontaneous breathing alternated with 30-s periods of isocapnic hyperpnea [spontaneous vs. voluntary: tidal volume = 0.5 +/- 0.01 vs. 1.3 +/- 0.1 (SE) liters and breath duration = 4.0 +/- 0.4 vs. 3.2 +/- 0.4 (SE) s]. For the group, voluntary hyperpnea was associated with significant (P < 0.05, corrected for multiple comparisons) neural activity bilaterally in the primary sensory and motor cortices, supplementary motor area, cerebellum, thalamus, caudate nucleus, and globus pallidum. Significant increases in activity were also identified in the medulla (corrected for multiple comparisons on the basis of a small volume correction for a priori region of interest) in a superior dorsal position (P = 0.012). Activity within the medulla suggests that the brain stem respiratory centers may have a role in mediating the voluntary control of breathing in humans.