MCI is considered an intermediate stage between normal cognitive aging and dementia. As such, improving cognitive functions of people with MCI may delay dementia onset. In recent years, tDCS, which regulates brain activity by increasing or decreasing brain tissue excitability, has become a commonly used brain stimulation method. Accumulating evidence indicates the promising effects of cognitive enhancement after tDCS over the frontal scalp regions in people with MCI (PwMCI). However, previous studies were limited by including only a self-report measure, focused on memory performance, not assessing long-term effect, and not reporting their results in follow-up. In addition, knowledge of the precise physiological consequences of tDCS on the brain tissue and related neural mechanisms in PwMCI remains rudimentary. The objectives of the proposed study, which will target PwMCI, are to investigate the effects of tDCS at the left dorsolateral prefrontal cortex on the cognitive performance and to explore the modulation of neural mechanisms associated with the use of tDCS. Forty-eight MCI participants aged over 60 years will be recruited. All participants will be assessed by Hong Kong version of Montreal Cognitive Test. Participants that meet selection criteria will be invited to the experiment. Participants will be assigned to experimental or control groups randomly. The experiment will consist of pre- and post-assessments and a 1-month follow-up assessment. Between pre- and post-assessments, participants will receive 8 sessions (2x/week for 4 weeks) of tDCS treatment (either real or sham, 20 min per session). Outcome measures include digit span test, colour trail test, verbal fluency test, Chinese version of the Verbal Learning Test , and Hong Kong version of Montreal Cognitive Assessment. Participants will also complete a computer memory task at each assessment point (performance in this task is also used as an outcome measure) and will have their brain wave recorded while completing the task. The task will require them to study and memorise Chinese characters, followed by a recognition memory test. In the study phase, participants will be required to view Chinese characters and judge whether the characters are of the animal category. In the recognition phase, participants will decide whether the characters have been seen before.

Randomization and blinding Due to limited available resources and the time required to collect the data, the investigators plan to implement the experiment in 4 batches, each separated by approximately two months. Each batch will include 12 participants from the same recruiting site. Six of them will be assigned to the anodal group and the other six to the sham group, using the block randomization method provided by http://www.randomization.com. The online software generates group allocation by knowing the number of participants per block (6) and number of blocks (2). Only the principal investigator will know the group assignments. Neither the participants nor the assessors will be given the information regarding the group assignments. Each participant will be given a registration number by the Principal Investigator. The tDCS device can be set to anodal or sham status. The PI will set up the tDCS device (anodal or sham) according to the participant's registration number and group through the device's administration menu. The research associate will select the stimulation protocol by inputting the participant's registration number on the device and be blinded to the participant's group assignment when performing tDCS stimulation and other assessments.

Sample size calculation The investigators used G*Power software to estimate the number of participants required to conduct repeated measure analyses of variance (within-between interactions) using the following parameters: correlation among repeated measures = 0.5, alpha = 0.05, number of groups = 2, power = 0.9 and number of measurements = 3 (assuming the correlation between repeated measures = 0.9). Effect size f is conservatively assumed to be 0.25. Based on previous experience using tDCS on participants with dementia and previous relevant studies, the investigators assumed a retention rate of 75%. Thus, the required sample size would be 48.

Procedure This proposed investigation will use a sham-controlled, randomized controlled trial. Participants will be randomly assigned to the anodal or sham groups (in 1:1 ratio). The stimulation method (anodal/sham) will be designated as the between-subject factor (independent variable). The potential participants will be screened and those who meet the selection criteria will be invited to participate in the study. Participants will attend a baseline assessment session in which the collection of demographic information, neurocognitive assessment scores, and a computer task with EEG recorded will occur, followed by 8 sessions of anodal tDCS completed twice a week for 4 weeks. Multi-session tDCS studies usually have a varied intervention schedule from 1 to 5 sessions per week for 1 to 5 weeks. The investigators have opted for this schedule to balance the time spent on intervention with its potential effectiveness, and to encourage compliance. After the intervention, participants will receive post- and 1-month follow-up assessments which will be the same as the baseline assessment.

EEG data acquisition EEGs will be recorded from 64 Ag/AgCl electrodes (BioSemi Active Two) located on the standard scalp sites of the 10/20 system. Four electrodes will be used to monitor eye blinks and movements. Two other electrodes will be placed in the mastoids for the EEG signal to be re-referenced off-line. Scalp EEG will be recorded from F3. Curry 9 software (Neuroscan Compumedics, U.S.A), or newer, will be used for the EEG signal processing. The EEGs will be sampled at 1024 Hz, with a low-pass filter of -200 μV. Digital band-pass filtering from 0.1 Hz to 30 Hz will be applied off-line. The continuous EEG signals will be segmented into epochs, from 200 ms before the stimulus to 1500 ms after the stimulus onset, and then the baseline will be corrected to the pre-stimulus interval. The epochs with amplitude ± 75 μV will be omitted from averaging. The averaged ERPs will be computed for each participant by classifying the study epochs that are correctly identified subsequently or missed during the recognition phase. Using the Curry 9 software, these averaged ERP files will then be transformed into text files with voltage (μV) and temporal information (ms) that can be read by Microsoft Excel software. After further rearrangement and processing in Excel, the data will be transferred to SPSS software for statistical analysis.

Inclusion Criteria:

• inexperienced with tDCS
• normal or corrected-to-normal vision
• right-handed
• independent in activities of daily living
• no history of seizures, head injuries, migraine, epilepsy or other psychiatric or neurological conditions

Exclusion Criteria:

• taking medication or supplements known to affect cognition (such as Ginkgo)
• exhibiting symptoms of emotional disorders
• having a history of cerebrovascular surgery
• with a metal plate in their skull