Effect of tDCS with an extracephalic reference electrode on cardio-respiratory and autonomic functions

Abstract

BackgroundTranscranial direct current stimulation (tDCS) is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. Its safety profile places tDCS in the pole-position for translating in real-world therapeutic application. However, an episode of transient respiratory depression in a subject receiving tDCS with an extracephalic electrode led to the suggestion that such an electrode montage could modulate the brainstem autonomic centres.We investigated whether tDCS applied over the midline frontal cortex in 30 healthy volunteers (sham n = 10, cathodal n = 10, anodal n = 10) with an extracephalic reference electrode would modulate brainstem activity as reflected by the monitoring and stringent analysis of vital parameters: heart rate (variability), respiratory rate, blood pressure and sympatho-vagal balance.We reasoned that this study could lead to two opposite but equally interesting outcomes: 1) If tDCS with an extracephalic electrode modulated vital parameters, it could be used as a new tool to explore the autonomic nervous system and, even, to modulate its activity for therapeutic purposes. 2) On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could thus be used safely in healthy human subjects. This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. Indeed, on the one hand, using an extracephalic electrode as a genuine neutral reference (as opposed to the classical "bi-cephalic" tDCS montages which deliver bi-polar stimulation of the brain) would help to comfort the conclusions of several modern studies regarding the spatial location and polarity of tDCS. On the other hand, using an extracephalic reference electrode may impact differently on a given cortical target due to the change of direct current flow direction; this may enlarge the potential interventions with tDCS.ResultsWhereas the respiratory frequency decreased mildly over time and the blood pressure increased steadily, there was no differential impact of real (anodal or cathodal) versus sham tDCS. The heart rate remained stable during the monitoring period. The parameters reflecting the sympathovagal balance suggested a progressive shift over time favouring the sympathetic tone, again without differential impact of real versus sham tDCS.ConclusionsApplying tDCS with an extracephalic reference electrode in healthy volunteers did not significantly modulate the activity of the brainstem autonomic centres. Therefore, using an extracephalic reference electrode for tDCS appears safe in healthy volunteers, at least under similar experimental conditions.

Polarity- and valence-dependent effects of prefrontal transcranial direct current stimulation on heart rate variability and salivary cortisol

“…These studies showed mixed findings. Vandermeeren et al (2010) applied anodal, cathodal or sham tDCS in 30 healthy volunteers, finding no specific effects on HRV. In this study, the active reference was over the midline frontal cortex and an extra-cephalic reference was used.…”

Nonlinear effects of respiration on the crosstalk between cardiovascular and cerebrovascular control systems

“…Despite this promising scenario and modelling work suggesting its feasibility in humans, just a handful of studies have investigated the application of tDCS for the modulation of cardiovascular human functions [125], with current literature showing very conflicting results [143,144]. Most of the studies involved the delivery of tDCS using a classic bipolar, cephalic electrode montage (i.e.…”

“…Whenever documented, positive autonomic effects of tDCS were related to anodal stimulation, with only two studies supporting effects for cathodal tDCS delivered on the DLPFC [146] or on M1, the latter addressing vasomotor reactivity changes [147]. However, only two studies were designed ad hoc to investigate the effect of tDCS on brainstem structures through a unipolar scalp montage linked with an extracephalic (arm/shoulder) electrode positioning: both studies, one targeting M1 [148] and the other one targeting the frontal midline [144], suggest null or mild effects on cardiovascular and respiratory functions, with a progressive shift over time in favour of the sympathetic tone, a finding that however was present during sham (i.e. placebo) tDCS.…”

Transcranial Current Brain Stimulation (tCS): Models and Technologies

“…Another method to avoid stimulating two brain regions simultaneously is to place one of the two electrodes below the neck [52]. Concern regarding stimulation of brainstem structures when using an extracephalic electrode may be unjustified [53]. Contrary to expectation, experimental evidence suggests that the duration and magnitude of after effects depends on the distance between the cranial and the extracephalic electrodes [54].…”