1. Participants
From June 2020 to February 2021, subjects aged 19 to 65 years with stress were recruited from the community. We placed an approved advertisement about the clinical trial on local newspapers, subways, and noticeboards of Seoul National University Bundang Hospital. Individuals with stress were defined according to their PSS, BDI-II, ISI, and STAI-S scores. Exclusion criteria included; (1) history of neurological deficit (dementia, brain injury, and seizure disorder), (2) presence of major psychiatric disorders (3) persons with acute stress (after the death of family, restraint, divorce, separation, debt, delinquency, affair, business failure, serious illness, marriage, etc.) within 4 weeks before the trial, (4) receiving cognitive behavioral therapy, biofeedback, neurofeedback, or meditation therapy within 1 year before the trial (5) taking psychotropic drugs, oral steroids or corticosteroids, health functional foods related to stress and sleep improvement within 2 weeks. Using the Beck depression scale as a measure of symptom improvement after the intervention, the minimum number of subjects was 36 for each group for the independent sample t-test to produce effect size 0.7 and power 0.9 under the 5% significance level.
All participants provided written informed consent. The trial was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB number, B-2006/616-304) and registered at the Clinical Research Information Service (CRiS registry number, KCT0007633, 09/08/2022). First recruitment date was June 23rd 2020. Guidelines and regulations were followed when performing all methods.
2. Measures
We performed the PSS, BDI-II, ISI, STAI-S, PSQI, and QOL-BREF questionnaires before and after the intervention. We also measured baseline and post-intervention QEEG to examine the objective effects of ASMR and BB.
1) Questionnaires
Participants filled out a PSS, BDI-II, ISI, and STAI-S questionnaires. Stress was defined according to PSS, BDI-II, ISI, and STAI-S scores. PSS is one of the most widely used stress scales that evaluates the subject's perceived stress experience on a 5-point Likert scale (0-4 points) during the past month.34 Since the tool was not developed for diagnostic purposes, the cut-off points are not separately presented, but 0-13 points are classified as low, 14-26 points as moderate, and 27-40 points as severe stress. Those with a PSS score of 14 or higher were determined as stressful. As stress can induce depressed mood, insomnia, and anxiety, we also included any one of the following in the criteria: BDI-II 20-45, ISI 8-21, or STAI-S >=39. The BDI-II is a self-report questionnaire assessing depressive symptoms in the past 2 weeks.15 It contains 21 items, and the total score ranges from 0 to 63. Scores of 0−13 were considered as not depressed, 14−19 as mildly depressed, 20−28 as moderately depressed, and 29−63 as severely depressed.35 The ISI is a 7-item self-report questionnaire assessing subjective insomnia. Its scores range from 0 to 28, and interpretation is as follows: 0-7 as the absence of insomnia, 8-14 as sub-threshold insomnia, 15-21 as moderate insomnia, and 22-28 as severe insomnia.36 The STAI-S is a self-report screening tool with 20 items to measure state anxiety, on a 4-point Likert scale. A cut-off point of 39 has been suggested for clinically significant symptoms of anxiety.37
2) Quantitative electroencephalogram (QEEG)
We recorded EEG for 7 minutes with eyes closed state followed by a 1-minute recording with eyes open state and 7 minutes with eyes closed state in a sitting position. All the subjects were instructed to keep their positions without movement to prevent muscle artifacts. We encouraged subjects to remain awake during the EEG measurements. EEG electrodes were placed according to the international 10–20 system with an average reference (FP1, FP2, F3, F4, F7, F8, C3, C4, P3, P4, T3, T4, T5, T6, O1, O2, average reference). The impedance of all the electrodes was below 5 kΩ. EEG signals were sampled at 1000 Hz and digitalized. The high pass filter was set to 100 Hz with the low pass filter set to 0.3 Hz. An artifact-free 120-s EEG recording with eyes closed (24 epochs of 5-s EEG segments) was selected by visual analysis. Artifacts such as muscle activity, small body movements, eyelids movements, and micro-sleep were not included. Absolute power values of five bands at each electrode were computed: delta (1.0–4.0 Hz), theta (4.0–8.0 Hz), alpha (8.0–12.0 Hz), beta (12.0–25.0 Hz), and high beta (25.0–30.0 Hz). Relative power values were computed as the percentage of absolute power.
3. Intervention
Subjects in the ASMR group listened to the ASMR sound. Since the ASMR sound can be uncomfortable for some people, we prepared three types of sounds: (1) scraping non-woven fabric sound, (2) birdsongs, and (3) white noise. Participants were allowed to choose one preferred sound and listened to it for 15 minutes during the daytime (before 2 PM) and 30 minutes at nighttime for 3 weeks. The music was automatically stopped after the intended periods by a predetermined setting in the application. In the morning, each subject completed a sleep diary, which included information about sleep latency, time in bed, awake after sleep onset, listening time, kind of music, and daytime sleepiness.
In the BB group, we used an application manufactured by Dlogixs, Inc. (Gyeonggi-do, South Korea), which produces a binaural beat, to stimulate brainwave production. In contrast to other devices that produce monotonous sounds with binaural beats, this product allows users to hear music without being aware of distortions of sound sources and resistance to monotonous sound. The audio apparatus shifts the frequency band as much as the target frequency from the original audio sound in real-time to generate binaural beats. We targeted an 8Hz binaural beat for daytime and a 5Hz binaural beat for nighttime. Three kinds of music were selected for the trial: (1) Debussy - Arabesque No. 1, (2) Mozart - Concerto for flute, harp & orchestra in C major, K. 299 (K. 297c), and (3) Mozart - Piano Concerto No. 21 in C, K 467, Elvira Madigan. The BB group participants listened to BB for 15 minutes during the daytime and 30 minutes at nighttime for 3 weeks. We judged good compliance as listening to the sound for at least 70 % of the sessions during the 3-week study period, based on the diaries. Same sets of smartphones and Bluetooth wireless earphones were provided to both groups.
4. Statistical analysis
SPSS version 22.0 for Windows (SPSS Inc. Chicago, IL, USA) was used for statistical analysis. All the results were reported as mean ± standard deviation (SD). The Kolmogorov-Smirnov test was used to confirm the normality of all the data. Independent t-test, χ2 test, or Mann-Whitney U test was used for baseline comparison of demographic characteristics, questionnaire data, and QEEG results between ASMR and BB groups. We examined within-group differences by using the paired t-test. Cohen’s d was calculated to estimate the effect size. Repeated measures analysis of variance (RM ANOVA) was used to confirm group-by-time interaction. For analysis of QEEG data, spectral analysis was done by fast Fourier transform. To normalize data distribution, absolute power was log-transformed. Relative power was chosen as a first principal analysis to reduce individual patient variation and bias between two recordings. We compared within-group differences of QEEG using the paired t-test in each group, and group-by-time interaction of all the QEEG power using RM ANOVA. All significance tests were two-sided and the p-value was set at < 0.05.
Data availability
The datasets of current study are available from the corresponding author on reasonable request.