Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, gliosis, and neuronal loss. Neurological symptoms may include visual disturbances, numbness and tingling, focal weakness, bladder and bowel incontinence, and cognitive impairment. Some previous studies have indicated that the NeuroBiofeedback (NBF) technique could be a promising new treatment for the rehabilitation of many neurological disorders and neurodegenerative diseases, including MS. Several studies have investigated the beneficial effects of this technique on the motor and cognitive outcomes of MS, mainly aiming to evaluate motor performance, fatigue and chronic pain. Few studies have focused on the evaluation and treatment of cognitive processes with NBF, except for one study on information processing speed. Specifically, regarding the application of NBF techniques in MS, recent literature has demonstrated that modulation of the alpha-theta rhythm has led to an improvement in attentional processes with consequent reduction in anxiety. Therefore, the objective of this study is to verify the effectiveness of NBF training on the modulation of cortical activity and physiological responses through the exposure of subjects with MS to cognitive tasks and training for mood regulation.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, gliosis, and neuronal loss. Neurological symptoms may include visual disturbances, numbness and tingling, focal weakness, bladder and bowel incontinence, and cognitive impairment. Some previous studies have indicated that the NeuroBiofeedback (NBF) technique could be a promising new treatment for the rehabilitation of many neurological disorders and neurodegenerative diseases, including MS. Several studies have investigated the beneficial effects of this technique on the motor and cognitive outcomes of MS, mainly aiming to evaluate motor performance, fatigue and chronic pain. Few studies have focused on the evaluation and treatment of cognitive processes with NBF, except for one study on information processing speed. Specifically, regarding the application of NBF techniques in MS, recent literature has demonstrated that modulation of the alpha-theta rhythm has led to an improvement in attentional processes with consequent reduction in anxiety. Therefore, the objective of this study is to verify the effectiveness of NBF training on the modulation of cortical activity and physiological responses through the exposure of subjects with MS to cognitive tasks and training for mood regulation.

Patients will not undergo an experimental procedure as foreseen by the study; the clinical and neuropsychological variables that will be collected for the study are those that are commonly collected by the neuropsychologist, in particular the main neuro-cognitive functions (memory, language, attention and executive functioning) and emotional abilities (meta cognition) will be considered. After enrollment, the clinical background and baseline characteristics of patients will be assessed. Enrolled patients will be randomly assigned to IG and SG. After randomization, patients will undergo instrumental examinations and neuropsychological evaluation, as required by the protocol. Patients in both groups will undergo 2 neurofeedback training sessions. All recruited subjects will be evaluated at two time-points: a first evaluation at baseline (T0) and at the end of the training (T1). Patients will undergo stimulation training via NBF 2 times a week for two months, for a total of 16 sessions. The procedure and execution of the training requires that the subjects are connected to a series of electrodes that will record the cortical electrical activity. During each session, IG patients will view their recorded brain waves and physiological responses in front of a computer screen, while a professional will explain to them what they need to do to intervene on what they see, in order to correctively modify their brain waves. While SG patients will be provided with irrelevant information (recorded data from other patients) and therefore will not be able to modulate their cortical activation

Inclusion Criteria:

• Patients aged 18-65 years ;
• Confirmed clinical diagnosis;
• Written informed consent obtained from the patient;
• Moca score ≥ 20;
• Patients with no contraindications to perform MRI and EEG.
• Clinical stability
• documented absence of relapse in the last month before treatment

Exclusion Criteria:

• Ascertained diagnosis of multiple pathologies,
• Patients with severe psychotic symptoms;
• Epilepsy;
• Drug use;
• Endocrine-metabolic encephalopathies.
• Presence of multiple therapies