Identification of sites of sympathetic outflow at rest and during emotional arousal: concurrent recordings of sympathetic nerve activity and fMRI of the brain.

The sympathetic nervous system subserves many of the autonomic responses to mental stress and emotional processing. While peripheral markers of sympathetic activity can be obtained indirectly - by measuring heart rate, blood pressure, sweat release and skin blood flow - these effector-organ responses are slower compared to the directly recorded sympathetic nerve activity. Microneurography, in which a tungsten microelectrode is inserted percutaneously into a peripheral nerve in awake human subjects, allows one to record sympathetic nerve activity to either muscle or skin. Muscle sympathetic nerve activity (MSNA) is involved in the beat-to-beat control of blood pressure, and is elevated during mental stress; chronic stress can lead to high blood pressure. The primary role of skin sympathetic nerve activity (SSNA) is to regulate body temperature by controlling sweat release and skin blood flow, but it has also been commandeered for emotional expression. In this review we discuss our recent work in which we have performed concurrent microelectrode recordings of MSNA or SSNA and fMRI of the brain, with a view to identifying areas in the brain responsible for generating the increases in sympathetic outflow at rest and during emotional engagement. Spontaneous bursts of MSNA at rest were positively correlated to activity in the left dorsomedial hypothalamus and left insula, and bilaterally in the ventromedial hypothalamus, dorsolateral prefrontal cortex, posterior cingulate cortex and precuneus. Spontaneous bursts of SSNA at rest were positively correlated with activity in the left ventromedial nucleus of the thalamus, the left posterior and right anterior insula, the right orbitofrontal and frontal cortices and bilaterally in the mid-cingulate cortex and precuneus. Increases in SSNA occurred when subjects viewed emotionally charged images, resulting in increases in activity in the central and lateral amygdala, dorsolateral pons, thalamus, nucleus accumbens, and cerebellar cortex; surprisingly, there was no activation of the insula in response to these emotional stimuli. We have shown that concurrent microelectrode recordings of sympathetic outflow to either muscle or skin and fMRI of the brain can be used to identify areas of the brain involved in the generation of sympathetic nerve activity. We propose that this approach can be extended to examine specific disorders of emotional expression to increase our understanding of the underlying neural processes.