Muscle sympathetic nerve activity (MSNA) controls the diameter of arterioles in skeletal muscle, contributing importantly to the beat-to-beat regulation of blood pressure (BP). While brain imaging studies have shown that bursts of MSNA originate in the rostral ventrolateral medulla, other subcortical and cortical structures—including the dorsolateral prefrontal cortex (dlPFC)—contribute. We tested the hypothesis that MSNA and BP could be modulated by stimulating the dlPFC. In 22 individuals MSNA was recorded via microelectrodes inserted into the common peroneal nerve, together with continuous BP, ECG and respiration. Stimulation of the right (n = 22) or left dlPFC (n = 10) was achieved using transcranial alternating current (tcACS; +2 to −2 mA, 0.08 Hz, 100 cycles), applied between the nasion and electrodes over the F3 or F4 EEG sites on the scalp. Sinusoidal stimulation of either dlPFC caused cyclic modulation of MSNA, BP and heart rate, and a significant increase in BP. We have shown, for the first time, that tcACS of the dlPFC in awake humans causes partial entrainment of MSNA, heart rate and BP, arguing for an important role of this higher-level cortical area in the control of cardiovascular function.

The dorsolateral prefrontal cortex (dlPFC) is primarily involved in higher order executive functions, with there being evidence of lateralization. Brain imaging studies have revealed its link to the generation of skin sympathetic nerve activity (SSNA), which is elevated in states of emotional arousal or anxiety. However, no studies have directly explored dlPFC influences on SSNA. Transcranial alternating current stimulation (−2 to 2 mA, 0.08 Hz, 100 cycles) was applied between the left or right dlPFC and nasion via surface electrodes. Spontaneous bursts of SSNA were recorded from the common peroneal nerve via a tungsten microelectrode in 21 healthy participants. The modulation index was calculated for each stimulation paradigm by constructing cross-correlation histograms between SSNA and the sinusoidal stimulus. Stimulation of the dlPFC caused significant modulation of SSNA, but there was no significant difference in the median modulation index across sides. Stimulation also caused cyclic modulation of skin blood flow and sweat release. We have shown for the first time that stimulation of the dlPFC causes modulation of SSNA, also reflected in the effector-organ responses. This supports a role for the dlPFC in the control of SSNA, which likely contributes to the ability of emotions to bring about cutaneous vasoconstriction and sweat release.