Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans

Abstract

1. 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. 2. 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. 3. 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. 4. 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. 5. 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.

Figure 1. Diagram of experimental design for acquisition of H₂¹⁵O-PET rCBF and physiological (Portapres) data

Subjects underwent 12 scans, representing 3 repetitions of 4 task conditions which were pseudorandomized in order within and between subjects: (1) effortful isometric exercise, (2) effortless isometric exercise control task, (3) effortful mental arithmetic (serial subtractions), and (4) effortless mental arithmetic control task (counting).

Figure 2. Changes in physiological measures during control tasks and during effortful isometric exercise and effortful mental arithmetic (mental stress) tasks

A, bar plot (means +s.d.) of changes in MAP (ΔMAP) for the 4 task conditions (increases in MAP from baseline during isometric exercise: effortful task, 24.9 ± 15.0 mmHg; effortless task, 8.5 ± 5.6 mmHg; P < 0.001, Student's t test; during mental arithmetic: effortful task, 16.2 ± 9.3 mmHg; effortless task, 5.6 ± 6.3 mmHg; P < 0.001). B, bar plot (means +s.d.) of changes in HR (ΔHR) for the 4 conditions (increases in HR from baseline during isometric exercise: effortful task, 16.2 ± 10.4 beats min⁻¹; effortless task, 4.2 ± 5.6 beats min⁻¹; P < 0.001; during mental arithmetic: effortful task, 13.6 ± 7.1 beats min⁻¹; effortless task, 3.7 ± 2.9 beats min⁻¹; P < 0.001).

Figure 3. Brain areas showing increased CBF during both stressor tasks compared to control conditions

Localized increases in rCBF common to effortful isometric exercise and effortful mental arithmetic conditions (minus their respective control conditions). Conjunction analysis of effortful vs. effortless exercise with effortful vs. effortless mental arithmetic was used to determine common increases in rCBF associated with performing the effortful tasks. Areas of significant common activation above P < 0.001 are colour scaled according to the Z-score (scale given in figure). Group data are presented on parasaggital and coronal slices of a standard template T1-weighted structural image derived from one subject, normalized to standard space (Talairach & Tournoux, 1988). Talairach co-ordinates in the x-dimension and y-dimension are given for parasaggital and coronal slices, respectively. The following areas are labelled: ac, cingulate area 32; p, pons; and cv, cerebellum (vermis).

Figure 4. Right anterior cingulate activity showing positive covariance with MAP in exercise and mental arithmetic tasks

Activity in the right anterior cingulate (ac) covaried significantly with increasing blood pressure. For all subjects regional activity covarying with MAP was computed for isometric exercise and mental arithmetic tasks. A conjunction analysis was then performed to identify brain areas in which rCBF positively covaried with MAP in both exercise and mental stress tasks. Voxels showing significant (P < 0.001, uncorrected) activity are depicted on a template T1-weighted structural image of a single subject. A, parasaggital view. B, coronal view. Regional rCBF activity (above P < 0.001, uncorrected) is colour scaled according to the Z-score (scale depicted in figure).