Theta oscillations over the posterior medial frontal cortex (pMFC) and lateral prefrontal cortex (LPFC) play vital roles in sustained attention. Specifically, pMFC power and pMFC-LPFC synchronization correlate with cognitive control in sustained-attention-related tasks, but the causal relationships remain unknown. In the present study, we first analyzed the correlation between EEG theta oscillations (characterized by time-frequency power and phase-based connectivity) and the level of sustained attention (Experiment 1) and then utilized transcranial alternating current stimulation (tACS) to modulate theta oscillations and in turn observed its effects on sustained attention (Experiment 2). In Experiment 1, two time-frequency regions of interest (ROIs) were determined, in which high/low time-frequency power and high/low phase-based connectivity corresponded to high/low-level sustained attention. In Experiment 2, time-frequency power and phase-based connectivity of theta oscillations were compared between the sham and tACS groups within the time-frequency ROIs determined in Experiment 1. Results showed that phase-based connectivity between pMFC and LPFC significantly decreased in the tACS group compared with the sham group during the first five minutes of the poststimulation period. Moreover, a marginal trend existed that sustained attention was downregulated by tACS in the same time interval, suggesting that theta phase synchronization between pMFC and LPFC may play a causal role in sustained attention.
Sustained attention could be defined as “the ability to self-sustain mindful, conscious processing of stimuli whose repetitive, non-arousing qualities would otherwise lead to habituation and distraction to other stimuli” [
A large number of studies have suggested that sustained attention correlates closely with cortical oscillations, extracted often from electroencephalography (EEG) signals. Integrated into the model proposed by Clayton et al., frontomedial theta (fm-theta) oscillations and the coordination between the posterior medial frontal cortex (pMFC) and the lateral prefrontal cortex (LPFC) play vital roles in sustained attention [
Transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique, is capable of providing causal evidence concerning the role of cortical oscillations in cognition [
The present study is aimed at investigating the causal roles of theta-band pMFC-LPFC oscillations in sustained attention via tACS. To this end, we conducted two close-knit experiments in two steps. In Experiment 1, we used EEG to explore whether and how theta-band pMFC-LPFC oscillations were correlated with sustained attention. Two types of EEG features—time-frequency power on pMFC and phase-based connectivity between pMFC and LPFC—were analyzed. Based on the correlative evidence between these two features and the sustained attention obtained from Experiment 1, we further conducted Experiment 2 by applying theta-tACS (6 Hz) to specifically modulate the power as well as phase synchronization between pMFC and LPFC to affect the behavioral performance of sustained attention. Experiment 2 was expected to provide causal evidence between theta-band pMFC-LPFC oscillations and sustained attention, which would be fundamentally helpful in advancing our understanding of the neural mechanisms of sustained attention.
A total of 10 volunteers (6 males, mean age
The psychomotor vigilance task (PVT) is a simple but mentally demanding reaction time test, which is often used in research on sustained attention and fatigue [
Schematic illustration of one trial in Experiment 1.
EEG signals were acquired from 64 Ag/AgCl scalp electrodes at 1000 Hz using the Neuroscan EEG acquisition apparatus (Neuroscan Inc., USA) according to the international 10-20 system. Electrode impedances were kept below 10 k
The RTs of the trials were computed in custom-written MATLAB programs. Firstly, to see the overall trend of sustained attention, we presented RTs averaged across all subjects. Secondly, all trials were rearranged sequentially from short to long RT. Then, the first one-third trials were grouped and analyzed as representing high-level sustained attention, and the last one-third trials were grouped and analyzed as low-level sustained attention, as similarly done in the previous study [
First, EEG data were segmented into epochs from -1000 ms to 1200 ms relative to the onset of the stimulus. According to RTs, the epochs corresponding to two levels of sustained attention, the same way as behavioral analysis did, were selected. Next, single-trial epochs were decomposed into their time-frequency representation via convolution with a family of complex Morlex wavelets, defined as Gaussian-tapered complex sine waves. Forty logarithmically spaced frequencies between 2 Hz and 40 Hz were utilized. The number of cycles increased from 3 to 10 in logarithmical steps. The convolution was conducted through frequency-domain multiplication, in which the Fourier-derived spectrum of epochs was multiplied by the spectrum of wavelets, and then, the inverse Fourier transform was performed. Power and phase were defined and thus extracted as the squared magnitude of the complex result and the angle relative to the positive real axis, respectively. Note that the power was normalized using a decibel (dB) transform (
Phase-based connectivity is also known as phase synchronization or phase coherence [
in which
The Fz and F3 electrodes were used to measure activities over pMFC and LPFC, respectively, consistent with prior studies [
Fifteen volunteers (8 males, mean age
In Experiment 2, we used a revised version of the psychomotor vigilance test (Figure
Schematic illustration of Experiment 2: (a) timeline of experiment events; (b) schematic illustration of one trial.
tACS was delivered by a battery-operated stimulator (DC-Stimulator Plus, neuroConn, Germany). The stimulator was connected to two Ag/AgCl electrodes with a 1 cm radius, which thus provided
For every participant under each stimulation (sham stimulation or tACS), the behavior baseline was defined by the sum of the mean and the standard deviation of reaction times in the first 5 minutes. To rule out the possible confounding effect of individual baseline differences, we chose not to compare RTs directly, but the proportions of negative responses as follows. First, we specified six time intervals, namely, 0-5 min, 5-10 min, …, 20-25 min, and 25-30 min, respectively. Next, within each time interval, the number of sad expressions was divided by the number of all expressions. Last, these ratios of sad expressions (i.e., proportions of negative responses) in six time intervals (within-subject factor, 6 levels) under two conditions (sham/tACS, within-subject factor, 2 levels) were compared using two-way repeated measures ANOVA. Furthermore, to investigate the immediate effects after stimulation, considering the nonuniformity of behavioral data in the current dataset, the Wilcoxon signed-rank test on paired samples was performed to compare sustained attention in the fifth time interval (20-25 min) between the sham and tACS groups. To justify the sample size involved in Experiment 2, we report effect size estimates used with the Wilcoxon signed-rank test where an effect size
Because EEG signals during the stimulation (5-20 min) were introduced large amounts of artifacts, so we only analyzed the signals right before the stimulation (0-5 min) and right after the stimulation (20-30 min). Artifacts were cleaned by first visual inspection and then ICA. On average, 20% of the trials were rejected. As a consequence, for every participant, approximately 40 trials remained in the first 5 minutes, and approximately 80 trials remained in the last 10 minutes. We used those 40 trials in the first 5 minutes to represent the state of sustained attention before stimulation, and those 80 trials in the last 10 minutes to represent the state of sustained attention after stimulation.
The time-frequency decomposition is the same as that in Experiment 1. The interested time-frequency windows determined in Experiment 1 were utilized to examine the difference between the sham and tACS groups. Within those windows, the averaged time-frequency power change at electrode Fz and the averaged phase-based connectivity change at Fz-F3 in the last two time intervals (i.e., 20-25 min and 25-30 min, within-subject factor, 3 levels), relative to the baseline (0-5 min), under two stimulations (i.e., sham and true tACS, within-subject factor, 2 levels) were compared using two-way repeated measures ANOVA. The relative change was used here due to different baseline states [
Furthermore, to investigate the immediate effects after stimulation, considering the nonuniformity of time-frequency data, the Wilcoxon signed-rank test on paired samples was performed to compare power and phase synchronization in the fifth time interval (20-25 min) between the sham and tACS groups, a similar way conducted in the previous tACS study [
Figure
The behavioral results in Experiment 1. (a) The averaged RTs were increasingly longer with the experimental time going on. Note the length of error bars is the standard deviation. (b) The averaged RTs of high-level sustained attention trials were significantly faster than those of low-level sustained attention trials (
Time-frequency power on the pMFC (electrode Fz) was averaged across all subjects under high-level and low-level sustained attention, respectively (Figures
Time-frequency power of pMFC (Fz). The power of (a) high-level and (b) low-level sustained attention (here abbreviated as SA) was computed by averaging across all subjects. (c) Districts circled in thin lines denote a significant difference between high-level and low-level sustained attention (high-level minus low-level). The bold black rectangle shows the interested time-frequency window (150-350 ms and 4-6 Hz). (d) The averaged power of high-level sustained attention was significantly larger than that of low-level sustained attention,
DWPLI between pMFC (Fz) and LPFC (F3) was averaged across all subjects under high-level and low-level sustained attention, respectively (Figures
Phase-based connectivity between pMFC (Fz) and LPFC (F3). DWPLI of (a) high-level and (b) low-level sustained attention (here abbreviated as SA) was computed by averaging across all subjects. (c) The difference between high-level and low-level sustained attention (high-level minus low-level) was demonstrated. The bold black rectangle shows the interested time-frequency window (150-300 ms and 5-8 Hz). (d) The averaged dWPLI of high-level sustained attention was significantly larger than that of low-level sustained attention,
Taken together, two different time-frequency windows were specified in which high-level sustained attention had both larger power and larger phase-based connectivity than low-level sustained attention in Experiment 1.
A two-way repeated measures ANOVA was run to determine the effect of different stimulations (sham/tACS) over time intervals (0-5, 5-10,…, 25-30 min) on sustained attention, represented by the proportions of negative responses. The interaction effect between stimulation and time intervals on sustained attention was not statistically significant,
(a) Sustained attention in the two stimulation groups (sham/tACS) both declined with experimental time going on. There were no significant interaction or stimulation effects, but there was a significant main effect of time intervals, and the post hoc comparisons can be found in Table
Multiple comparisons of time intervals in behavioral results.
Group 1 | Group 2 | Statistic | Significance |
---|---|---|---|
TI 1 (0-5 min) | TI 2 (5-10 min) | -3.46 | |
TI 1 (0-5 min) | TI 3 (10-15 min) | -4.09 | |
TI 1 (0-5 min) | TI 4 (15-20 min) | -3.71 | |
TI 1 (0-5 min) | TI 5 (20-25 min) | -5.07 | |
TI 1 (0-5 min) | TI 6 (25-30 min) | -5.54 | |
TI 2 (5-10 min) | TI 3 (10-15 min) | -2.63 | |
TI 2 (5-10 min) | TI 4 (15-20 min) | -1.83 | |
TI 2 (5-10 min) | TI 5 (20-25 min) | -3.22 | |
TI 2 (5-10 min) | TI 6 (25-30 min) | -5.18 | |
TI 3 (10-15 min) | TI 4 (15-20 min) | 0.331 | |
TI 3 (10-15 min) | TI 5 (20-25 min) | -0.92 | |
TI 3 (10-15 min) | TI 6 (25-30 min) | -3.14 | |
TI 4 (15-20 min) | TI 5 (20-25 min) | -1.71 | |
TI 4 (15-20 min) | TI 6 (25-30 min) | -3.86 | |
TI 5 (20-25 min) | TI 6 (25-30 min) | -2.98 |
Note: significant effects are marked by asterisks and bold text.
A two-way repeated measures ANOVA was run to determine the effect of different stimulations (sham/tACS) over time intervals (20-25 min and 25-30 min) on the averaged power change relative to baseline (0-5 min) within the time-frequency window (150-350 ms, 4-6 Hz) determined in Experiment 1 (Figure
A two-way repeated measures ANOVA was run to determine the effect of different stimulations (sham/tACS) over time intervals (20-25 min and 25-30 min) on the averaged dWPLI changes relative to the baseline (0-5 min) within the time-frequency window (150-300 ms, 5-8 Hz) determined in Experiment 1 (Figure
To investigate pMFC-LPFC oscillations in the process of sustained attention, we first analyzed the correlation between theta characteristics (time-frequency power and phase-based connectivity) and the level of sustained attention and then utilized tACS to modulate theta characteristics and in turn observed its effects on sustained attention. In Experiment 1, two interested time-frequency windows were determined, in which high/low time-frequency power and high/low phase-based connectivity (indexed by dWPLI) corresponded to high/low-level sustained attention. In Experiment 2, time-frequency power and phase-based connectivity were compared between sham stimulation and tACS groups within the time-frequency window determined in Experiment 1. There was no significant difference in time-frequency power between the two stimulation groups. However, phase-based connectivity between pMFC and LPFC significantly decreased in the tACS group compared with the sham group during the first five minutes of the poststimulation period. Moreover, there was a marginal trend that sustained attention was downregulated by tACS in the same time interval, suggesting that theta phase synchronization between pMFC and LPFC may play a causal role in sustained attention.
In Experiment 1, the reaction time gradually increased as the experimental time went on, suggesting that the level of sustained attention gradually went down. This phenomenon, called vigilance decrement, was commonplace in PVT tasks [
In Experiment 2, there were no significant differences in time-frequency power and performance of sustained attention between the sham and tACS groups. However, trends were shown that in the first five minutes during the poststimulation period, namely, 20-25 min (the fifth time interval), sustained attention was probably downregulated by tACS. Most importantly, in the fifth time interval, phase-based connectivity between pMFC and LPFC significantly decreased in the tACS group compared with the sham group. These facts probably implied the causal relationship between sustained attention and theta phase synchronization between pMFC and LPFC. A large number of studies suggested that tACS with different phase differences can manipulate phase synchronization [
There have been several similar studies in which theta band tACS over the pMFC was used to modulate sustained attention. For example, Rostami et al. aimed to modulate pMFC to influence sustained attention [
There are also some limitations to our study. The first limitation is our sample size across two experiments. We recruited 10 subjects in experiment 1 and 15 subjects (only 12 could be analyzed) in Experiment 2. It is better to collect more data to get more robust results, especially for signal analysis in tACS. The second limitation of our study is the lack of a 0° tACS comparison set in Experiment 2. tACS with 180° phase difference used in our study mainly came from the bipolar setting of the stimulator. Next, high-density tACS could be used to realize 0° tACS [
The present study is aimed at investigating the causal roles of theta-band pMFC-LPFC oscillations in sustained attention via tACS. Results showed that in the first five minutes after tACS was terminated, theta-band phase-based connectivity between pMFC and LPFC significantly decreased; meanwhile, sustained attention had a declining trend. These findings implied the causal relationship between sustained attention and theta phase synchronization between pMFC and LPFC.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there is no conflict of interest regarding the publication of this paper.
This work was supported by the National Natural Science Foundation of China (Nos. 51377120 and 51007063).