To achieve our aims, we planned a double-blind, randomized, prospective, controlled study. To this purpose, we will recruit 80 MS subjects affected by cognitive impairment (CI). Patients will be selected from outpatients attending the Department of Neurology of ASL3 Genoa and the Neurorehabilitation unit of IRCCS Ospedale Policlinico San Martino, Genoa. The participants will be randomly assigned to two groups, 40 in the experimental group (EG), 40 in the control group (CG), matched for demographic data (gender, age), EDSS and disease duration. All subjects will undergo a cognitive training by means of the exergames system (10 sessions, one hour per session, 5 days per week, for two consecutive weeks). Patients in the EG group will undergo a simultaneous A-tDCS over the left DLFPC, while CG will receive a S-tDCS over the same area. The tDCS will be delivered by a battery-driven, constant current simulator with a LCD touch screen (HDC progr), a portable stimulator (HDC stim), two holding bags of plant cellulose (7x5 cm) and two electrodes of conductive silicone. The active (anodal) electrode will be placed by means of a cap on the scalp overlying the left DLPFC (46 Brodmann Area). The reference electrode will be located over the right shoulder. The choice of the left DLPFC as the site of stimulation relies upon the evidence that this region has a critical role in the "top-down" control of the task-relevant stimuli processing .
In addition, in tasks where a cognitive conflict arises, the DLPFC contributes to increased cognitive control through its connections with the anterior cingulate cortex . Finally A-tDCS of the DLPFC has been shown to enhance working memory and executive function in healthy subjects as well as in PwMS . An electroconductive gel will be applied under the electrodes in order to reduce contact impedance. Impedance will be constantly kept below 5 kOhm. Only the tDCS investigators will be aware of the type of stimulation, while the patients and the neuropsychological assessors will be blind as to the nature of the project. During the exergames training (on-line procedure), A-tDCS (current of 1,5 mA) will be delivered for 20 minutes, while maintaining the current density (0.06 mA/ cm2) below the safety limits . In the StDCS session (20 minutes) the current will be turned off 30 sec after the beginning of the stimulation and turned on for the last 30 sec. By doing this, the patient feels an itching sensation below the electrodes at the beginning and at the end of stimulation, making this condition indistinguishable from the real (anodic) stimulation. Doing this, all the subjects will be blinded on the type of stimulation (anodal or sham). All the patients will participate to the cognitive training by means of exergames, which includes motor and cognitive tasks that incorporate enjoyment, technology, and health care.
