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.
Highlights
Transcranial direct current stimulation is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability
Using an extracephalic reference electrode for (transcranial direct current stimulation) (tDCS) appears safe in healthy volunteers, at least under similar experimental conditions
We deliberately decided to apply 20 minutes of 1 mA tDCS because 1) these parameters were used in the majority of the modern tDCS studies, 2) the blinding of healthy subjects is questionable when using high tDCS intensities such as 3 mA, and 3) this study was designed as a first step towards other experiments exploring different parameters. Conclusions this comprehensive study expands and confirms recent reports suggesting a lack of interference of tDCS with an extracephalic reference electrode with vital functions [20,21,22,23,34,35], it has several limitations
Summary
Transcranial direct current stimulation (tDCS) is used in human physiological studies and for therapeutic trials in patients with abnormalities of cortical excitability. 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. 2) On the opposite, if applying tDCS with an extracephalic electrode had no effect, it could be used safely in healthy human subjects This outcome would significantly impact the field of non-invasive brain stimulation with tDCS. It is generally admitted that the effects of tDCS are less focal than those of rTMS and despite the development of realistic head models uncertainties remain about the distribution of the direct current (DC) within the brain. An episode of transient respiratory depression in a healthy volunteer under frontal tDCS with an extracephalic reference electrode suggested that this electrode montage could lead to a modulation of the brainstem respiratory centres [14,15]. When Nitsche and Paulus meticulously expanded the seminal findings of the impact of tDCS on the primary motor cortex (M1) excitability described by Priori and collaborators [16,17,18], they cautiously banned the use of an extracephalic electrode and proposed the “classical” montage for modulating M1 excitability with tDCS: the “active” electrode over the target M1 and the other “reference” electrode over the contralateral orbita [19]
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