Cheree James

Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally-charged images

The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

Real-time imaging of cortical and subcortical control of muscle sympathetic nerve activity in awake human subjects

Blood pressure is controlled on a beat-to-beat basis through fluctuations in heart rate and the degree of sympathetically-mediated vasoconstriction in skeletal muscles. By recording muscle sympathetic nerve activity (MSNA) at the same time as performing functional magnetic resonance imaging (fMRI) of the brain, we aimed to identify cortical structures involved in central cardiovascular control in awake human subjects. Spontaneous bursts of MSNA were recorded via a tungsten microelectrode inserted percutaneously into the peroneal nerve of 14 healthy subjects in a 3T MRI scanner. Blood Oxygen Level Dependent (BOLD) contrast - gradient echo, echo-planar - images were continuously collected in a 4s ON, 4s OFF sampling protocol. MSNA burst amplitudes were measured during the OFF periods and BOLD signal intensity was measured during the subsequent 4s period to allow for neurovascular coupling and nerve conduction delays. Group analysis demonstrated regions showing fluctuations in BOLD signal intensity that covaried with the intensity of the concurrently recorded bursts of MSNA. Signal intensity and MSNA were positively correlated in the left mid-insula, bilateral dorsolateral prefrontal cortex, bilateral posterior cingulate cortex and bilateral precuneus. In addition, MSNA covaried with signal intensity in the left dorsomedial hypothalamus and bilateral ventromedial hypothalamus (VMH). Construction of a functional connectivity map revealed coupling between activity in VMH and the insula, dorsolateral prefrontal cortex, precuneus, and in the region of the left and right rostroventrolateral medulla (RVLM). This suggests that activity within suprabulbar regions may regulate resting MSNA by projections to the premotor sympathetic neurons in the rostroventrolateral medulla.

Real-time imaging of cortical areas involved in the generation of increases in skin sympathetic nerve activity when viewing emotionally charged images.

The sympathetic innervation of the skin not only primarily subserves thermoregulation, but has also been commandeered as a means of emotional expression. While the majority of brain imaging studies of emotion have utilised the galvanic skin response as a means of inferring changes in skin sympathetic nerve activity (SSNA), spontaneous fluctuations in the galvanic skin response bear little relation to spontaneous fluctuations in SSNA. To improve our understanding of the central neural processes involved in the generation of autonomic emotional markers, we recorded SSNA concurrently with brain functional magnetic resonance imaging in 13 subjects. Emotional changes were evoked by presentation of positively-charged (erotica) or negatively-charged (mutilation) images from the International Affective Picture System. Positive and negative emotionally-charged images evoked significant increases in total SSNA and signal intensity in the orbital, dorsolateral and ventromedial prefrontal cortices, amygdala, nucleus accumbens and anterior insula. Increases in signal intensity during increases in SSNA occurred in a number of brain regions, including the central and lateral amygdala, dorsolateral pons, thalamus, nucleus accumbens, and cerebellar cortex. Signal intensity decreases during SSNA increases occurred in the left orbitofrontal, frontal and right precuneus cortices. These data reveal for the first time, cortical and subcortical sites involved in generating SSNA changes during emotions.

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.

Real-time imaging of brain areas involved in the generation of spontaneous skin sympathetic nerve activity at rest.

In thermoneutral conditions resting skin sympathetic nerve activity (SSNA) is related to the level of arousal and emotional state. The brain regions responsible for the generation of spontaneous SSNA are not known. In the present study we used concurrent recordings of SSNA and brain activity in awake humans to identify cortical and subcortical areas involved in the generation of spontaneous SSNA in 13 healthy subjects. Blood oxygen level dependent signal intensity increases covaried with SSNA in the left thalamus in the region of the ventromedial nucleus, the left posterior and right anterior insula, the right orbitofrontal cortex, the right frontal cortex, and bilaterally in the mid-cingulate cortex and precuneus. Functional connectivity analysis revealed a strong positive coupling between the right orbitofrontal cortex and the right anterior insula. Furthermore, signal intensity changes within the precuneus were temporally coupled to the left anterior and posterior insula, cerebellum, cingulate cortex and thalamus. It has been hypothesized that these brain regions monitor the internal state of the body and may regulate emotional state changes. Our results show that the activities within these regions are also correlated to spontaneous fluctuations in SSNA.

Competitive interactions between vestibular and cardiac rhythms in the modulation of muscle sympathetic nerve activity

We tested the hypothesis that vestibular and cardiac rhythms compete to modulate muscle sympathetic nerve activity (MSNA) in human subjects. Sinusoidal galvanic vestibular stimulation was applied across the mastoid processes at each subjects cardiac frequency and at ±0.1, ±0.2, ±0.3 and ±0.6 Hz. Cyclic modulation of MSNA was weakest at this central frequency (44.8±2.3%; n=8); significantly lower than when delivered 0.1 Hz lower (57.7±3.3%) or 0.1 Hz higher (56.3±3.3%) than this frequency. We conclude that vestibular inputs compete with baroreceptor inputs operating at the cardiac rhythm, with vestibular modulation of MSNA being lowest when competition with the baroreceptors is highest.

Identification of Sites of Sympathetic Outflow During Concurrent Recordings of Sympathetic Nerve Activity and fMRI

The sympathetic division of the nervous system is critical for maintaining both resting arterial pressure and for producing changes in regional perfusion required by behavioral state changes. A primary determinant of arterial pressure is the level of vasoconstriction within skeletal muscle. It is well established that there is a tight relationship between dynamic changes in arterial pressure and muscle sympathetic nerve activity (MSNA) through the workings of the baroreflex. While the central circuitry underlying the baroreflex has been extensively investigated in anesthetized experimental animals, few studies have investigated the central circuitry responsible for the baroreflex in awake human subjects. Recently we were the first to record concurrently MSNA (using microneurography) and brain activity (using functional magnetic resonance imaging) in awake humans in a series of experiments designed to determine the central circuitry underlying the baroreflex in humans. We confirmed that the baroreflex involves activity changes within the nucleus tractus solitarius, caudal ventrolateral, and rostral ventrolateral medulla. Because conditions such as essential hypertension, obesity, and obstructive sleep apnea are all characterized by significant increases in resting MSNA, it is important to understand both brainstem and cortical sites involved in regulating resting levels of MSNA. Future investigations which define cortical sites involved in generating and modulating MSNA are important if we are to understand the underlying mechanisms of many conditions characterized by hypertension. Anat Rec, 2012.