Electrical stimulation of the midbrain increases heart rate and arterial blood pressure in awake humans

Abstract

Electrical stimulation of the hypothalamus, basal ganglia or pedunculopontine nucleus in decorticate animals results in locomotion and a cardiorespiratory response resembling that seen during exercise. This has led to the hypothesis that parallel activation of cardiorespiratory and locomotor systems from the midbrain could form part of the 'central command' mechanism of exercise. However, the degree to which subcortical structures play a role in cardiovascular activation in awake humans has not been established. We studied the effects on heart rate (HR) and mean arterial blood pressure (MAP) of electrically stimulating the thalamus and basal ganglia in awake humans undergoing neurosurgery for movement disorders (n = 13 Parkinson's disease, n = 1 myoclonic dystonia, n = 1 spasmodic torticollis). HR and MAP increased during high frequency (> 90 Hz) electrical stimulation of the thalamus (HR 5 +/- 3 beats min(-1), P = 0.002, MAP 4 +/- 3 mmHg, P = 0.05, n = 9), subthalamic nucleus (HR 5 +/- 3 beats min(-1), P = 0.002, MAP 5 +/- 3 mmHg, P = 0.006, n = 8) or substantia nigra (HR 6 +/- 3 beats min(-1), P = 0.001, MAP 5 +/- 2 mmHg, P = 0.005, n = 8). This was accompanied by the facilitation of movement, but without the movement itself. Stimulation of the internal globus pallidus did not increase cardiovascular variables but did facilitate movement. Low frequency (< 20 Hz) stimulation of any site did not affect cardiovascular variables or movement. Electrical stimulation of the midbrain in awake humans can cause a modest increase in cardiovascular variables that is not dependent on movement feedback from exercising muscles. The relationship between this type of response and that occurring during actual exercise is unclear, but it indicates that subcortical command could be involved in 'parallel activation' of the locomotor and cardiovascular systems and thus contribute to the neurocircuitry of 'central command'.

Figure 1. Cardiovascular response to midbrain stimulation in an awake patient

Top panel illustrates stereotaxic placement of electrode in patient. Bottom panel: raw data trace showing the cardiovascular effects of electrical stimulation of the subthalamic nucleus (frequency 100 Hz, voltage 1 V then increased to 4 V, pulse width 1 ms) in an awake Parkinson's patient. Electrical stimulation results in an increase in heart rate (HR) and mean arterial pressure (MAP) that is maintained for the duration of the stimulation.

Figure 2. Group data (n = 9 thalamus, n = 8 STN and substantia nigra, n = 8 GPi) for the effects of high frequency electrical stimulation on HR (A) and MAP (B)

Filled bars are control, open are during stimulation. Thalamus refers to either the ventralis intermedius (n = 8) or ventralis oralis posterior nuclei (n = 1). Stimulation parameters were 0.5 ± 0.2 ms pulse width, frequency 100 Hz, 1.3 ± 0.2 V (thalamus), 0.5 ± 0.1 ms, 100 ± 3 Hz, 1.5 ± 0.2 V (STN), 0.4 ± 0.2 ms, 101 ± 1 Hz, 1.9 ± 0.4 V (SN). All data are means ± s.e.m. STN, subthalamic nucleus. * P < 0.05, ** P < 0.01; NS, not significant; paired t test.

Figure 3. Group data (n = 3 thalamus, n = 5 STN, n = 4 SN, n = 7 GPi) for the effects of low frequency electrical stimulation on HR (A) and MAP (B)

Filled bars are control, open are during stimulation. Thalamus refers to either the ventralis intermedius (n = 2) or ventralis oralis posterior nuclei (n = 1). STN, subthalamic nucleus. There was no significant change in HR or MAP during low frequency stimulation of any nucleus. Stimulation parameters were 0.5 ± 0.3 ms pulse width, frequency 3 ± 1 Hz, 2.2 ± 0.2 V (thalamus), 0.5 ± 0.2 ms pulse width, frequency 14 ± 9 Hz, 2.1 ± 0.3 V (STN), 0.5 ± 0.2 ms pulse width, frequency 18 ± 12 Hz, 1.6 ± 0.3 V (SN). All data are means ± s.e.m.