Time Course of Corticospinal Excitability and Autonomic Function Interplay during and Following Monopolar tDCS

Abstract

While polarity-specific after-effects of monopolar transcranial direct current stimulation (tDCS) on corticospinal excitability are well-documented, modulation of vital parameters due to current spread through the brainstem is still a matter of debate, raising potential concerns about its use through the general public, as well as for neurorehabilitation purposes. We monitored online and after-effects of monopolar tDCS (primary motor cortex) in 10 healthy subjects by adopting a neuronavigated transcranial magnetic stimulation (TMS)/tDCS combined protocol. Motor evoked potentials (MEPs) together with vital parameters [e.g., blood pressure, heart-rate variability (HRV), and sympathovagal balance] were recorded and monitored before, during, and after anodal, cathodal, or sham tDCS. Ten MEPs, every 2.5-min time windows, were recorded from the right first dorsal interosseous (FDI), while 5-min epochs were used to record vital parameters. The protocol included 15 min of pre-tDCS and of online tDCS (anodal, cathodal, or sham). After-effects were recorded for 30 min. We showed a polarity-independent stabilization of cortical excitability level, a polarity-specific after-effect for cathodal and anodal stimulation, and an absence of persistent excitability changes during online stimulation. No significant effects on vital parameters emerged both during and after tDCS, while a linear increase in systolic/diastolic blood pressure and HRV was observed during each tDCS condition, as a possible unspecific response to experimental demands. Taken together, current findings provide new insights on the safety of monopolar tDCS, promoting its application both in research and clinical settings.

Keywords: neuromodulation; safety; transcranial direct current stimulation; transcranial magnetic stimulation; vital parameters.

Figure 1

Experimental details. (A) Shows the experimental set-up with active-reference electrode positionings, the neuronavigated TMS coil placement over the active electrode, and settings for the EMG and vital parameter recordings. (B) Reports the time course of data acquisition, illustrating the different time windows utilized in the statistical analysis. MEPs and vital parameters were acquired, respectively, every 2.5 and 5 min. Analysis was performed on both high-resolution data and 15 min collapsed windows (before, during, tDCS, post 1 and post 2). Additional vital parameter and MEP data were collected 5 min before and after the experiment, in order to obtain basal-level values for data normalization.

Figure 2

Time course of tDCS effects. (A) Shows the high-resolution time course of MEP values for sham (green line), anodal (red line), and cathodal (blue line) tDCS conditions. Time points define different experimental conditions, namely pre-tDCS (2.5–15′), online tDCS (17.5–30′, gray band), post-tDCS1 (32.5–45′), and post-tDCS2 (47.5–60′). The y-axis refers to the corticospinal excitability values normalized using baseline MEPs acquired 5 min before the experiment for each condition. Each time point represents the average value of eight consecutive MEPs acquired within the 2.5 s wide window. Asterisks indicate time points showing a significant difference with respect to S-tDCS (p < 0.05). (B) Represents the average percentage of increase or decrease in cortical excitability for A-tDCS and C-tDCS respect with S-tDCS (straight line).

Figure 3

Collapsed time windows analysis. (A) Shows corticospinal excitability values collapsed in the 15 min before, 15 min during, 15 min post-1 and 30 min post-2 each tDCS condition. A repeated measures ANOVA highlighted significant differences between C-tDCS and S-tDCS/A-tDCS during the first 15 min after the stimulator had been switched off, while A-tDCS induced an increase in the average MEP level during the second 15 min blocks (post-tDCS2) with respect to S-tDCS and C-tDCS. (B) Reports tDCS condition-wide corticospinal excitability values showing a significant difference between post-tDCS2 compared to online tDCS for A-tDCS, as well for post-tDCS1 and 2 with respect to online tDCS during C-tDCS. P values refer to Bonferroni corrected pairwise comparisons.

Figure 4

Correlations between corticospinal excitability and vital parameters. (A) Shows the results of partial correlation analyses between vital parameters and MEP amplitudes computed by properly converting the latter to a 5-min time window resolution. The last matrix rows refers solely to motor evoked potential correlation coefficients (color-coded according to the right side bar) for different tDCS conditions, with Pearson’s r coefficients and P values reported for sympathovagal parameters, showing a significant correlation. Insert A₁ highlights the increased positive correlation between systolic (sBP), diastolic (dBP), mean blood pressure (mBP), and LFnu-RRI values during anodal stimulation, and the negative correlation between these values and HFnu-RRI (*p < 0.05; ⁺p < 0.01). Significant values entered a further linear regression analysis, whose results are shown in (B). A linear fit line with confidence intervals and the amount of variance in vital parameters explained by MEP values (R²) are reported.