Electrical stimulation of the ventromedial prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure.

We recently showed that transcranial alternating current stimulation of the dorsolateral prefrontal cortex modulates spontaneous bursts of muscle sympathetic nerve activity, heart rate, and blood pressure (Sesa-Ashton G, Wong R, McCarthy B, Datta S, Henderson LA, Dawood T, Macefield VG. Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans. Cereb Cortex Comm. 2022:3:2tgac017.). Stimulation was delivered between scalp electrodes placed over the nasion and electroencephalogram (EEG) electrode site F3 (left dorsolateral prefrontal cortex) or F4 (right dorsolateral prefrontal cortex), and therefore the current passed within the anatomical locations underlying the left and right ventromedial prefrontal cortices. Accordingly, we tested the hypothesis that stimulation of the left and right ventromedial prefrontal cortices would also modulate muscle sympathetic nerve activity, although we predicted that this would be weaker than that seen during dorsolateral prefrontal cortex stimulation. We further tested whether stimulation of the right ventromedial prefrontal cortices would cause greater modulation of muscle sympathetic nerve activity, than stimulation of the left ventromedial prefrontal cortices. In 11 individuals, muscle sympathetic nerve activity was recorded via microelectrodes inserted into the right common peroneal nerve, together with continuous blood pressure, electrocardiogram, and respiration. Stimulation was achieved using transcranial alternating current stimulation, +2 to -2 mA, 0.08 Hz, 100 cycles, applied between electrodes placed over the nasion, and EEG electrode site FP1, (left ventromedial prefrontal cortices) or FP2 (right ventromedial prefrontal cortices); for comparison, stimulation was also applied over F4 (right dorsolateral prefrontal cortex). Stimulation of all three cortical sites caused partial entrainment of muscle sympathetic nerve activity to the sinusoidal stimulation, together with modulation of blood pressure and heart rate. We found a significant fall in mean blood pressure of ~6 mmHg (P = 0.039) during stimulation of the left ventromedial prefrontal cortices, as compared with stimulation of the right. We have shown, for the first time, that transcranial alternating current stimulation of the ventromedial prefrontal cortices modulates muscle sympathetic nerve activity and blood pressure in awake humans at rest. However, it is unclear if this modulation occurred through the same brain pathways activated during transcranial alternating current stimulation of the dorsolateral prefrontal cortex.