Increasing human brain excitability by transcranial high-frequency random noise stimulation

Abstract

For >20 years, noninvasive transcranial stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS) have been used to induce neuroplastic-like effects in the human cortex, leading to the activity-dependent modification of synaptic transmission. Here, we introduce a novel method of electrical stimulation: transcranial random noise stimulation (tRNS), whereby a random electrical oscillation spectrum is applied over the motor cortex. tRNS induces consistent excitability increases lasting 60 min after stimulation. These effects have been observed in 80 subjects through both physiological measures and behavioral tasks. Higher frequencies (100-640 Hz) appear to be responsible for generating this excitability increase, an effect that may be attributed to the repeated opening of Na(+) channels. In terms of efficacy tRNS appears to possess at least the same therapeutic potential as rTMS/tDCS in diseases such as depression, while furthermore avoiding the constraint of current flow direction sensitivity characteristic of tDCS.

Figure 1.

The output signal of DC-Stimulator PLUS, as a frequency distribution of the signal, the time plot of the signal, and a histogram. The signal was generated by a computer. In the stimulation mode “noise,” there is a random level of current generated for every sample (sampling rate 1280 samples/s). The random numbers are normally distributed; the probability density function follows a bell-shaped curve. The amplitude of 1 mA pp means that 99% of all generated amplitude values were between +500 μA and −500 μA.

Figure 2.

Effect of 10 min RN stimulation on motor-evoked potentials. Time course of motor cortex excitability changes lasting for 60 min after stimulation, shown after 10 min RN stimulation over M1 at 1 mA compared with sham stimulation. The figure shows mean amplitudes and their SEMs up to 60 min (including all subjects, n = 17) and between 90 min and 24 h (including 8 subjects). Asterisks indicate significant differences between MEP amplitudes after 5 and 10–60 min after stimulation and those at baseline.

Figure 3.

Effect of 10 min of low (0.1–100 Hz)- and high (101–640 Hz)-frequency RN stimulation on motor-evoked potentials. Time course of motor cortex excitability changes lasting for 60 min after stimulation, shown after 10 min of high-frequency RN stimulation over M1 at 1 mA compared with low-frequency and sham stimulation. The figure shows mean amplitudes and their SEMs up to 60 min (including all subjects, n = 12).

Figure 4.

tRNS of the primary motor cortex improves implicit motor learning in its early phase. Reaction times decrease faster in the tRNS condition when compared with the sham stimulation condition (top). Moreover, the RT difference comparing blocks 5 and 6, which indicates implicit sequence learning, is bigger for the tRNS condition, when compared with sham condition. The asterisk indicates a significant difference regarding reaction time differences between blocks 5 and 6 between RN and sham stimulation. In 1 and 2 h after stimulation, this significant difference was no longer detectable (bottom panels).