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The Effects of Transcranial Direct Current Stimulation on Performance and Recovery Sleep during Acute sleep Deprivation

Background: Previous studies have claimed that transcranial direct current stimulation (tDCS) on the left dorsolateral prefrontal cortex (dlPFC) improves cognition in patients, but few studies that have evaluated the effects of tDCS on cognition improvement during sleep deprivation. To determine whether tDCS (anodal on the left DLPFC and cathodal on the right DLPFC at 2mA current for 30 minutes) can be an effective fatigue countermeasure. Methods: Seven participants and 8 participants underwent active or sham tDCS on the time participants’ cognition declined, respectively. All participants completed the psychomotor vigilance task, the trail making test A and B, the digit cancellation test, the stroop color word test, the brief visuospatial memory test-revised and a procedural game every two hours during the sleep deprivation and after recovery sleep. Results: The active tDCS had beneficial effects on attention, memory, executive function, processing speed, and the ability to inhibit cognitive interference, as well as improvements of subjective drowsiness and fatigue during sleep deprivation. The lasting effect of single tDCS on cognition during sleep deprivation can extend to more than 2 hours. All participants after tDCS gained no disturbed recovery sleep and recovered to baseline cognitive level after the recovery sleep. Conclusions: The study indicated that tDCS is an effective fatigue countermeasure during sleep deprivation, and doesn’t disturb the recovery sleep and performance postrecovery sleep.

decrements in mood and mental performances, and increase the risk of accidents. Sleep deprivation can result in feelings of fatigue, loss of vigor, sleepiness, confusion, increased reaction time, decreased accuracy and decreased attention. Williamson et al. [1] found that after 17 h of continued wakefulness, participants had performance equivalent to individuals with a blood alcohol concentration of 0.05%, which is considered illegal to drive a car in most countries. Unfortunately, many occupations require shifts lasting even longer than this; therefore, it is necessary to investigate possible fatigue countermeasures.
Transcranial direct current stimulation (tDCS) is a method to noninvasively stimulate the brain. In this procedure, weak and direct current (1-2 mA) is applied through electrodes that are placed on the scalp to induce alterations in cortical activity and excitability.
Anodal stimulation produces a net increase in neuron excitability in the area of stimulation while cathodal stimulation causes a net decrease in excitability. The brain region of interest varies by task; if a researcher is interested in improving fine motor control they will attach electrodes above the motor cortex [2]; if they are interested in improving working memory, sustained attention [3] and mood regulation [4], they will attach electrodes above the dorsolateral prefrontal cortex (DLPFC). Based on previous research, tDCS of the DLPFC can modulate attention [5], arousal, decrease excessive daytime sleepiness, and counter fatigue [6][7][8]. We hypothesize that tDCS can be an effective fatigue countermeasure to improve attention, vigilance, memory, processing speeding, and executive function during sleep deprivation. The aims of the study were to

Procedures
All participants were required to wake up at 6:00 am and arrive to the lab before 7:00 am on the day of sleep deprivation. Participants underwent blood pressure, pulse rate, respiratory rate, and temperature test every hour from 8:00 am. Participants completed the Psychomotor vigilance task (PVT) [9], the Trail making test A and B (TMT-A, TMT-B) [10], the digit Cancellation test (DCT) [11], the Stroop color and word test A and B (SCWT-A and SCWT-B) [12], the Brief visuospatial memory test-revised (BVMT-R) [13], the Fatigue visual analog scale, the Stanford Sleepiness Scale (SSS), and the Karolinska Sleepiness Scale (KSS) every two hours. They were required to play electrical games to keep their concentration on screen during the gaps between every two hours tests. Coffee, cigarettes, and alcohol were forbidden during the study.
The declined reaction time of PVT at least 30 ms from the previous ones or 5 lapses were used as the primary parameters to determine the time to deliver tDCS. TDCS (2 mA, 30 min) was delivered by a direct current stimulator (neuroConn, Germany), connected to two electrodes, one on the scalp over the left DLPFC ( F3 in 10-20 EEG system, anode) and the other above the right DLPFC ( F4 in 10-20 EEG system, cathode). Stimulating electrodes were thick (0.3 cm) square (35 cm 2 ) pieces of saline-soaked synthetic sponge.
For safety, multistage monitoring of the output current and electrode/tissue impedance was included. The device automatically shuts off if the impedance becomes greater than 50 kΩ to prevent electric shocks or burns. A constant current of 2 mA over each stimulation electrode for 30 min was applied in a 15 s fade-in/fade-out design to decrease potential skin sensations. For sham stimulation, the current turned off automatically after 15 s fade-in/fade-out. Researchers companied with the participants to remind them to keep alert to do the tests, and decided the time to deliver tDCS. All participants and researchers were blind to the electrical tests. Researchers input the random numbers to the tDCS machine according to subsequence of participants needed to be delivered tDCS.
As the active tDCS and sham tDCS may cause different electrical senses, the researchers were factually not blind after the tDCS performed.
After tDCS treatment, participants continued to perform all the same tests procedures as before until completion of the 10:00 am session tests. According to the PVT, if participants could not recovery, they were arranged to sleep with the monitoring of polysomnograph (PSG) to the time they wanted to get up, or they continued to do the tests until the PVT declined sharply. After participants got up, they performed the last session of tests.

Sleep Examination
PSG ( Philips ) were performed and analyzed according to The AASM Manual for the Scoring of Sleep and Associated Events 2.5 version (AASM 2.5).
Personal computer (PC) -PVT 2.0 [9] which was documented to comparable to PVT-192 was used to assess the effects of sleep deprivation on human neurobehavioral performance.
TMT A and B [10] provide information on visual search, scanning, processing speed, mental flexibility, and executive functions. We used the computer version of TMT of which the location of numbers and letters are random each time. TMT-A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on the screen by mouse. Task requirements are similar for TMT-B except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task.
DCT is used to assess attention deficits [11,14]. DCT was once a paper and pencil test.
We programmed it to computer version according to 1992 version [11], that is the 1-digit target matrix acted as a buffer-trial, and test-scores turned out from the 2-and 3-digits targets matrices. The PC-DCT, devised for this study on the basis of the discriminant powers of each matrix among different time of sleep deprivation, provided three variations of the procedures: 1) the mouse is instead of pencil, the screen instead of paper, 2) digits have to be crossed out are random in each tests, 3) digits have to be crossed out within different time-limits, 10 s/matrix, 20 s/matrix, 30 s/matrix, and 45 s/matrix to assess attention, vigilance, memory, processing speeding, and executive function. As 10 s/matrix is too short and 45 s/matrix is too long to evaluate the sensitivity of performance, we just analyzed the 20 s/matrix, 30 s/matrix scores.
SCWT is widely used to multiple cognitive functions, such as the ability to inhibit cognitive interference, attention, processing speed, cognitive flexibility, and working memory [12]. E-Prime 2.0 software was used to perform SCWT. SCWT-A was to choose the color of the ink of the word, while SCWT-B test was to choose the color of reading the word. Each test has 72 random color-word items, in which 36 are color-word in incongruous condition, 36 in congruous condition. Every item color-word shows on the screen for 2000 ms, the 250 ms black screen duration to next item of color-word. When red is chosen, participants are required to click the keyboard D as fast and correctly as they can. Similarly, green click F, yellow click J, blue click K.
BVMT-R is a measure of visual learning and memory [13]. Simply speaking, a visual display of six simple figures randomly arranged in a 2 × 3 matrix on paper is shown to participants for three consecutive 10-second trials. After each trial, participants are to draw as many designs as accurately as they can and in the correct location. The scores should consider the accuracy of both the shape and location.

Analysis
Because treatment conditions started at different time session, the session occurring before the treatment was the last time point at which all participants were treated the same. The last session before treatment was treated as baseline. It was compared the change from the last session before treatment to the first session after treatment to help determine an transient effect of stimulation, and the change from the last session before treatment to the second session after treatment to help determine a 'after term' effect of stimulation. It was compared the change from the session at 10:00 am on the first day to the session after recovery sleep to determine recovery effect. Difference between active and sham groups were assessed at baseline and changes using student t-test for normally distributed continuous variables, and Mann -Whitney U-tests for non-normal continuous variables. These analyses were performed by SPSS for Windows, version 22.0 (SPSS Inc., Chicago, IL, USA). The level of significance was selected at p < 0.05.

Results
The study was one part of study which studied the effect of tDCS on cognition, recruited 57 health male, average age 23.61 ± 1.62 years (range 21-27 years). Twenty participants were underwent this part of study, in which 8 participants were delivered with 2 mA, 30 min tDCS on F3 anode F4 cathode (active group), 12 participants were in the sham tDCS group (sham group). Seven participants in active group and 8 in the ham group were analyzed ( Fig. 1). All participants had PVT mean reaction time declined within 18 to 28 hours extended wakefulness. There were no statistically difference in the extended wakefulness time to performing tDCS (p = 0.773) between active group (21.4 h ± 1.57 h) and sham group (20.75h ± 3.20 h). The t-tests exposed no difference of minor lapses

Transient Effect of tDCS
The t-tests exposed a significantly better outcome of major lapses (≥ 1000 ms) of PVT (p  (Table 2 and Fig. 2-6)          flexibility, processing speed, and working memory than sham group, but it also had aftereffects on visual search, scanning, processing speed, mental flexibility and executive functions that remain at least 2 h when compared to sham group. The duration of lasting after-effects is dependent on stimulation duration and number of treatments [15]. Our data suggest that single 30 min of stimulation produces behavioral after effects lasting at least 2 h. Previous study reported 30 min of stimulation produces behavioral after effects lasting at least 6h [7]. The improvement in cognitive performance with tDCS was accompanied by lower subjective ratings for fatigue and drowsiness. Thus, not only did the participants with tDCS (anodal on left DLPFC and cathode on the right DLPFC 2 mA 30 min) perform better, but they also felt less tired and sleepy than their counterparts given sham tDCS interventions. This was accordance with previous study [7]. Besides, compared with the tests of 10 o'clock session, at which cognition was thought as the best of the day, the postrecovery sleep performance recovered to or showed better than presleep deprivation levels in both tDCS and sham groups, which was similar to administration of caffeine, dextroamphetamine, and modafinil [16]. This is the first study compared the postrecovery sleep effect on cognitive performance of tDCS improvement during extended wakefulness,which indicated that recovery sleep is still the best fatigue countermeasure.  [20]. Fourthly, the study used the decrease of PVT mean reaction time as the standardization to delivery tDCS, which caused some sample didn't had enough time to observe the after effect of tDCS.

Conclusions
Our findings suggested that anode tDCS applied to the left DLPC and cathode tDCS to the right DLPC 2 mA for 30 min had beneficial effects on attention, the ability to inhibit cognitive interference, memory, processing speeding, and executive function during the beginning periods of sleep-deprivation induced fatigue. Additionally, the tDCS-induced performance benefits were coupled with improvements in subjective drowsiness and fatigue. The lasting effect of single tDCS on cognition during sleep deprivation can extend to more than 2 h. This is the first data to suggest that tDCS may have no disadvantages on recovery sleep after sleep deprivation and cognition can soon get recovery to baseline level after the recovery sleep. Given these initial promising findings, we conclude that tDCS should be further examined as an intervention for fatigue and sleep.

Consent to publish
Not applicable.

Availability of data and materials
The datasets during and/or analysed during the current study available from the corresponding author on reasonable request. Legend not available in this version Legend not available in this version Legend not available in this version Legend not available in this version Legend not available in this version

Supplementary Files
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