Anodal Transcranial Direct Current Stimulation Induces High Gamma-Band Activity in the Left Dorsolateral Prefrontal Cortex During a Working Memory Task: A Double-Blind, Randomized, Crossover Study

Abstract

Transcranial direct current stimulation (tDCS) has been shown to have mixed effects on working memory (WM) capacity in healthy individuals. Different stimulation paradigms may account for these discrepancies, with certain features being favored. To determine the effect in the context of anodal tDCS, we investigated whether anodal tDCS induced cortical oscillatory changes during a WM task. Specifically, we tested whether anodal offline tDCS over the left prefrontal cortex (PFC) enhances WM capacity by modulating the oscillatory activity in the left dorsolateral PFC (DLPFC) using magnetoencephalography (MEG). This study employed a double-blind, randomized, crossover design, in which 24 healthy right-handed participants conducted MEG recordings during a 3-back task after administration of 2 mA tDCS or sham stimulation as a placebo. Our results showed that the effect of tDCS did not appear in the behavioral indices-WM accuracy (d') or reaction time (RT). From the results of the time-frequency analysis, significant event-related synchronization (ERS) in the high-gamma band (82-84 Hz) of the left DLPFC was found under the tDCS condition; however, ERS was not correlated with WM capacity. Furthermore, we calculated the modulation index (MI), which indicates the strength of phase-amplitude coupling (PAC). tDCS significantly decreased MI of the left DLPFC, representing the theta-gamma PAC during the n-back task using color names as verbal stimuli. Our results suggest that although tDCS increased the gamma-band oscillation indicating greater neural activity in the left DLPFC, it did not lead to an improvement of WM capacity; this may be due to the inability of gamma-band oscillation to couple with the task-induced theta wave. WM capacity might not increase unless theta-gamma PAC is not enhanced by tDCS.

Keywords: DLPFC; MEG; color; n-back task; phase-amplitude coupling; tDCS; working memory.

Figure 1

(A) Study design: a double-blind, randomized, crossover design was employed. Twenty-four participants were recruited and randomly assigned to receive either transcranial direct current stimulation (tDCS) or Sham stimulation during the first session. After a washout period of at least 1 month, the second session was conducted. (B) Task flow of the experiments in each session: practice of the n-back task was conducted in the order of 1-, 2-, and 3-back conditions. tDCS or sham stimulus as a placebo was administrated. Two sponge electrodes, anode and cathode were on the F3 and F4 according to the international 10–20 system, respectively. Electrodes were removed and preparation for magnetoencephalography (MEG) recordings in a shielded room was initiated. The first MEG task was an auditory task reported in Miyagishi et al. (2018). The 3-back task was started approximately 25 min after the end of stimulation.

Figure 2

Schematic figure of an experimental block showing three conditions and the corresponding 3-back responses: stimuli for the Word condition are represented here in English instead of Japanese Kana used within the tDCS-MEG study. *Means that no response is needed.

Figure 3

Box plots with individual participant data of (A) d′ and (B) reaction time (RT): stars denote significant difference at p < 0.05.

Figure 4

Effect of intervention on oscillatory cortical activity: event-related spectral perturbation (ERSP) plots from the results of time-frequency analysis are given for the tDCS condition and Sham condition in the left and right dorsolateral prefrontal cortex (DLPFC). The bottom panels show the results of the permutation t-test (tDCS—Sham). The rectangle regions surrounded by a dotted line indicate significant event-related synchronization (ERS) or desynchronization (ERD) with false discovery rate (FDR) correction (p < 0.05).

Figure 5

Box plots with individual participant data of percent signal change in (A) the left DLPFC and (B) the right DLPFC. Data from the left DLPFC were extracted from 270 to 600 ms at 82–84 Hz, and data from the right DLPFC were extracted from 1,180 to 1,400 ms at 47–49 Hz, during which tDCS had significant effects. Stars denote the significance at p < 0.05; however, the stars indicating the significant main effect of intervention are omitted. Scatter plots (C,D) show the correlation between d′, indicating working memory (WM) capacity, and percent signal change that appeared above in the (A) left and (B) right DLPFC, respectively. The results of correlation analysis (Pearson’s correlation coefficient, r) at each intervention are shown in (C,D).

Figure 6

(A) Box plots with individual participant modulation index (MI) data showing the strength of phase-amplitude coupling (PAC) in the left DLPFC: stars denote significant difference at p < 0.05. (B) Scatter plots showing the correlation between d′, and MI.