Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans

Abstract

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.

Figures

Figure 1. Course of the study

In the beginning of each session, 20 baseline single-pulse MEPs of SI1mv intensity, resting motor threshold (RMT), active motor threshold (AMT), input–output (I–O) curve, I-waves, short-latency intracortical inhibition, intracortical facilitation (SICI-ICF) and cortical silent period (CSP) were recorded. Afterwards, 2 or 1 mA tDCS over 20 min was administered and then the above-mentioned parameters were recorded again. From 60 min after the stimulation, single- and double-pulse TMS parameters were recorded as follows: single-pulse MEPs of SI1mv intensity, RMT, AMT and SICI-ICF 60, 90 and 120 min after the end of tDCS and at the evening on the same day (∼18:00; SE = same evening). For Experiment 1 we also performed these measurements on the next morning (∼9:00; NM), next noon (∼12:00; NN) and next evening (∼18:00; NE).

Figure 2. After-effects of anodal and cathodal tDCS on single-pulse MEP amplitudes

A–C, after-effects of (A) 2 mA anodal and 2 mA cathodal tDCS (number of participants = 14), (B) 2 mA cathodal and 1 mA cathodal tDCS (number of participants = 9) and (C) sham tDCS (number of participants = 8) on the single-pulse MEP amplitudes (means ± SEM) at the TMS intensity which elicited 1 mV MEP amplitudes at baseline. Asterisks indicate significant differences of MEP amplitudes from baseline values (P < 0.05). Anodal stimulation at 2 mA shows a significant increase of MEP amplitudes 60 and 90 min after stimulation, compared with 2 mA cathodal stimulation 90 and 120 min after tDCS. Cathodal stimulation at 1 mA shows a significant decrease in MEP amplitudes at 0–120 min after stimulation. Sham tDCS did not induce any significant changes.

Figure 3. Intracortical inhibition and facilitation is modulated by tDCS

A–D, single-pulse standardized double stimulation MEP amplitude ratios ± SEM are depicted for ISIs revealing inhibitory (ISIs of 2, 3 and 5 ms) and facilitatory (ISIs of 10 and 15 ms) effects for (A) 2 mA anodal, (B) 2 mA cathodal, (C) 1 mA cathodal and (D) sham tDCS. Anodal tDCS at 2 mA decreases inhibition and increases facilitation immediately after stimulation for ISIs of 5 and 10 ms and 60 and 90 min after stimulation for an ISI of 5 ms; similar effects were observed 90 and 120 min after 2 mA cathodal tDCS. After 1 mA cathodal tDCS, facilitation is decreased for an ISI of 10 ms immediately after stimulation and inhibition is increased for ISIs of 5 ms at 90 min and 3 and 5 ms at 120 min after stimulation. Sham tDCS did not induce any significant changes. Asterisks indicate significant differences of standardized double stimulation MEP amplitudes from respective before stimulation values (P < 0.05).

Figure 4. Effect of 1 mA cathodal tDCS on input–output curve

MEP amplitudes (means ± SEM) are displayed before and after application of 1 mA cathodal tDCS. A trend towards a decrease of MEP amplitudes after tDCS can be observed, in line with a previous study of our group (Nitsche et al. 2005).