1. Introduction
It seems that in patients with unilateral stroke, during Serial Reaction Time Task(SRTT) training, along with transcranial direct current stimulation (tDCS), physical condition and psychophysical factors such as fatigue, attention, motivation, the difficulty level of exercise, pain, or any discomfort during tDCS may affect the implicit motor learning process of stroke patients [1, 2].
Evaluation of adverse effects of tDCS on neurological patients has shown that adverse effects of stimulation include itching 39%, discomfort 10%, headache 14%, and burning sensation 22% [3]. Although no significant complication in tDCS treatment has been reported on the motor learning process of stroke patients, due to the importance of this issue in rehabilitation, more studies are needed on the effects and possible adverse effects of tDCS on the motor learning process in stroke patients. This study aimed to evaluate the effects and adverse effects of tDCS on motor learning in patients with chronic unilateral stroke.
2. Methods
This cross-sectional, sham-controlled, randomized, and blinded study was performed in 2020 as a sample on 12 patients with chronic unilateral stroke with a Mean±SD age of 60.33±1.87 years and duration after the lesion was 1.96±1.36 which were referred to Kashani Clinic in Hamadan. Patients were randomly divided into two experimental groups (Serial reaction time task (SRTT)+Dual transcranial direct current stimulation (dual-tDCS)) and Sham (SRTT+Sham dual-tDCS). Six patients in the experimental group received 1 mA stimulation for three consecutive days with a dual-tDCS assembly electrode for 20 minutes while practicing SRTT; While 6 patients in the sham group received Sham dual -tDCS sham stimulation (SRTT) for three consecutive days while practicing SRTT motor learning. In Sham dual-tDCS stimulation, there was a gradual increase in current for only 1 minute at the beginning of the stimulation, and the current was interrupted for the remaining 20 minutes so that the person did not notice the current throughout the stimulation session [4].
SRTT exercise was designed and performed with Response pad hardware model RB-740 and Superlab5 software. Each SRTT session consisted of 8 blocks with one minute of rest between the two blocks. Each exercise block was repeated 8 times, and each exercise session contained 8 stimulus responses. In each training session, blocks 1 and 6 had a random pattern, and there was no logical relationship in the order of their emergence, while the other SRTT blocks had a predetermined regular pattern.
After 3 weeks (washing out period), patients in each of the two stimulation groups were re-intervened in the other group of brain stimulation. In order to collect data on implicit motor learning of patients, the time after the stimulus appeared to the response of the individual’s movement was recorded as the reaction time, and the percentage of response to the irrelevant stimulus was recorded as the percentage of error [5]. The Visual Analogue Scale (VAS) questionnaire was also used to assess patients’ tDCS adverse effects, pain or discomfort, attention level, and fatigue [6, 7].
In this study, first, the necessary explanations were given to the stroke patients about the research objectives and the method of implementation, and after signing the consent form, the patients participated in the study. The protection of the subjects’ personal information and the principle of confidentiality was observed in the study, and patients were assured that they could withdraw from the cooperation at any stage of the research. In addition, after the research, rehabilitation services for patients were provided free of charge.
3. Results
The results of paired t-test showed that a suitable time was selected to eliminate the effect of tDCS. The most-reported sensation in patients was itching and tingling, which persisted throughout the stimulation sessions. Also, none of the patients reported adverse effects such as headaches during brain stimulation sessions.
In order to investigate the effect of patients’ attention, fatigue, and pain on the learning process, the statistical test of the linear mixed-effects model was used. The results showed that the effect of type of brain stimulation, time, and the interaction of time and type of stimulation on patients’ fatigue, attention, and the pain was not significant (P>0.05). In addition, the cause of pain or discomfort of patients during the test sessions was very small and ranged from 1 to 2 on a 10-point scale. Figures 1 and 2 show the trend of reaction time and normalized error of patients for three consecutive days in two groups of brain stimulation. The graphs show a gradual reduction of reaction time and a gradual reduction of motor block error during three days of training in two groups of brain stimulation. Also, the difference between reaction time and error of blocks with regular and random patterns in all three days of motor learning training and in both brain stimulation groups was observed in the charts, which showed a significant improvement in implicit motor learning in both brain stimulation groups.







4. Discussion
The present study results showed that implicit motor learning of patients with mild stroke significantly increased during three consecutive days of SRTT training with healthy hands of patients in both tDCS groups. Also, the type of tDCS stimulation and the intervention time during three days did not affect the patients’ fatigue, attention, and pain. Evaluation of behavioral changes using tDCS treatment techniques to improve motor behaviors with less psychophysical effects and adverse effects can save treatment costs and time [8-10]. Appropriate features of the tDCS device such as non-invasiveness, minimal side effects, transient side effects along with its very comfortable tolerance without pain or discomfort of the patient make tDCS be recognized as an effective and efficient strategy in increasing the rate of implicit motor learning of stroke patients and healthy individuals [8-10].
Ethical Considerations
Compliance with ethical guidelines
This study was registered (Code : IR.CT20160705028808N5 on the Iranian Registry of Clinical Trials. The ethical approval of this study was confirmed by the Ethics Committee of Hamadan University of Medical Sciences in 2020 (Code: IR.UMSHA.REC.1399.344). All ethical principles were considered in this study. All participants signed a consent form that explained the study aims.
Funding
This study was extracted from research project No.: 9904312721 approved by Hamadan University of Medical Sciences. Which was done with the financial support of the Vice Chancellor for Research and Technology of Hamadan University of Medical Sciences.
Authors' contributions
Determining the objectives of the research: Eileen Talimokhani, Iraj Abdollahi, Mohammad Ali Mohseni Bandapi and Mehrdokht Mazdeh; Research: Eileen Talimokhani, Mehrdokht Mazdeh and Bahareh Rezaei; Data analysis and collection: Eileen Talimokhani, Iraj Abdollahi; Editing and finalizing the article: Eileen Talimokhani, Iraj Abdollahi, Mohammad Ali Mohseni Bandapi, Mehrdokht Mazdeh and Bahareh Rezaei. All authors have read and approved the final version.
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgments
This study was derived from research project No.: 9904312721 approved by Hamadan University of Medical Sciences. The authors appreciate the financial and nonfinancial supports of the university’s Vice Chancellor for Research and Technology and the patients who participated in the study.