Introduction: The dorsolateral prefrontal cortex (dlPFC) is primarily involved in higher-order executive functions, and little is known of its role in control of the autonomic nervous system. Our brain imaging studies have revealed links between the dlPFC and the generation of muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA) in humans (Macefield et al., 2013; Macefield & Henderson, 2016, 2019). We recently showed that sinusoidal electrical stimulation of the dlPFC causes a cyclic modulation of MSNA, heart rate and blood pressure, but had no effect on respiration (Sesa-Ashton et al., 2022). Here we assessed whether stimulation of the dlPFC can also modulate sympathetic outflow to skin. Methods: Spontaneous bursts of SSNA were recorded from cutaneous fascicles of the right common peroneal nerve via a tungsten microelectrode in 21 healthy participants. Negative-going sympathetic spikes were extracted from the neurogram. Low-frequency sinusoidal stimulation (-2 to 2mA, 0.08 Hz, 100 cycles) was applied to the right dlPFC (EEG electrode site F4, n=21) or left dlPFC (F3, n=12) and the nasion via surface electrodes. The modulation index (peak-trough/peak) was calculated for each stimulation paradigm by constructing cross-correlation histograms between the times of occurrence of the sympathetic spikes and the peak of the sinusoidal stimulus. Results: Sinusoidal stimulation of either the right or left dlPFC caused significant cyclic modulation of SSNA (Mann-Whitney, p<0.01), but there was no side-to-side difference. Stimulation also caused cyclic modulation of skin blood flow and sweat release. Conclusions: We have shown that sinusoidal stimulation of the dlPFC causes modulation of sympathetic outflow to skin as well as muscle in humans, as directly recorded via intraneural microelectrodes, as well as modulation of their effector-organ responses. This supports an important role for the dlPFC in the control of the sympathetic nervous system, which likely contributes to the ability of mental stress to bring about increases in MSNA, heart rate and blood pressure, and emotions to bring about increases in SSNA, cutaneous vasoconstriction and sweat release.
Physiology 2023 (Harrogate, UK) (2023) Proc Physiol Soc 54, C66
Oral Communications: Sinusoidal electrical stimulation of the dorsolateral prefrontal cortex modulates sympathetic nerve activity to muscle and skin in humans
Vaughan Macefield1, Rebecca Wong1, Gianni Sesa-Ashton1, Brendan McCarthy1, Sudipta Datta1, Luke Henderson1, Tye Dawood1,
1Department of Neuroscience, Monash University Melbourne Australia, 2Baker Heart and Diabetes Institute Melbourne Australia, 3Baker Department of Cardiometabolic Health, Melbourne University Melbourne Australia, 4School of Medical Sciences (Neuroscience), Brain and Mind Centre, The University of Sydney Sydney Australia,
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Where applicable, experiments conform with Society ethical requirements.