Function Magnetic Resonance Imaging to Assess Two Therapeutic Strategies in Multiple Sclerosis (NeuroRehEM).

Study Overview
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Brief Summary
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Multiple sclerosis (MS) is an autoimmune disease that causes cognitive and motor disabilities and contributes to decrease patients life quality. Previous results described that there are some MS patients that showed (at least in some phases of the disease) neuroplasticity processes that are able to compensate some cognitive deficits. Moreover, neuroplasticity processes seem to be limited and related to the degree of gray matter atrophy (patients with less atrophy show grater neuroplasticity than those with higher atrophy level). The aims of this project are: to study behavioral changes (post-training) induced by two different rehabilitation programs: a)cognitive training focused on exclusively enhancing working memory and b) aerobic + cognitive training aimed to enhance attention, working memory processes and motor capabilities using a virtual reality game. to study neuroplasticity changes (post-training functional connectivity changes) induced by these rehabilitation programs to observe the role of the atrophy in brain neuroplasticity processes. Neuropathological status and neuroplasticity processes (studied using neuroimaging tools) as well as cognitive performance using neuropsychological tools will be assessed in a group of MS patients (with different phenotypes) at two different time points: before any training (S1) and after 10 days of training (S2). This project will be financed by the Ministerio de ciencia, innovación y universidades of the Spanish government and also have been approved by the Ethical committee of Universitat Jaume I.

Official Title
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Neurorehabilitation and Functional Recovery in Multiple Sclerosis: Assessing Two Therapeutic Strategies Using Functional Magnetic Resonance Imaging.

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Behavioral: N-back Cognitive Training
* Behavioral: Virtual Reality Motor and Cognitive Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Multiple Sclerosis Diagnosis. Exclusion Criteria: Other neurological pathologies comorbidity. Magnetic resonance imaging incompatibilities. Motor impairment degree that impede the task performance.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Working Memory Training in MS patients<br>This group of patients will perform a computerized n-back training, which includes a sequence of 2-back and 3-back blocks. | Behavioral: N-back Cognitive Training<br>* N-back task mainly trains working memory and information processing speed. This training lasts 10 days (1 hour per day).<br>|
| Experimental: Virtual Reality Training in MS patients<br>This group of patients will perform a Virtual Reality Ball Task training. This task contains 6 trials of increasing difficulty. | Behavioral: Virtual Reality Motor and Cognitive Training<br>* Virtual Reality Ball Task mainly trains inhibitory control, attention, working memory and motor functions. This training lasts 10 days (30 minutes per day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Correct Responses | Number of correct responses in both tasks (n-back computerized task and balls Virtual Reality task) | Baseline and 10 training days after. | 
| Change from baseline in Reaction Time | This is a primary outcome of the n-back task, which refers to the amount of time (in milliseconds) that elapse from the moment the correct stimulus appears and the correct response is given. | Baseline and 10 training days after. | 
| Change from baseline in Omissions | In both tasks will be assessed the number of times that a correct stimulus appear and non-response is given. | Baseline and 10 training days after. | 
| Change from baseline in Errors | The number of times that a distractor stimulus appears and a response is given. | Baseline and 10 training days after. | 
| Change from baseline in Functional Connectivity in resting state | This is a brain activity measure during resting state through functional magnetic resonance imaging. This outcome will be assessed in both studies. fMRI sequence: T2-weighted echoplanar imaging sequence. | Baseline and 10 training days after. | 
| Change from baseline in Functional Connectivity in task performance | This is a brain activity measure during a task performance through functional magnetic resonance imaging. This outcome will be assessed in Virtual Reality study. fMRI sequence: T2-weighted echoplanar imaging sequence. | Baseline and 10 training days after. | 
| Change from baseline in SRT-S: Selective Reminding Test (Storing) | A subtest of the BRB-N (The Brief Repeatable Battery of Neuropsychological Tests for MS) which measures memory storage capacity. | Baseline and 10 training days after. | 
| Change from baseline in SRT-R: Selective Reminding Test (Retrieval) | This subtest of the BRB-N is a measure of memory retrieval capacity. | Baseline and 10 training days after. | 
| Change from baseline in SRT-D: Selective Reminding Test (Delayed) | This BRB-N subtest measures the delayed memory. | Baseline and 10 training days after. | 
| Change from baseline in SPART: Spatial Recall Test | A subtest of the BRB-N that measures spatial memory. | Baseline and 10 training days after. | 
| Change from baseline in SPART-D: Spatial Recall Test (Delayed) | This BRB-N subtest measures the spatial delayed memory. | Baseline and 10 training days after. | 
| Change from baseline in SDMT: Symbol Digit Modalities Test | A BRB-N subtest which measures information processing speed. | Baseline and 10 training days after. | 
| Change from baseline in PASAT: Paced Auditory Serial Addition Task | A BRB-N subtest which measures working memory. | Baseline and 10 training days after. | 
| Change from baseline in Phonemic Fluency | A language measure that assesses phonemic fluency. | Baseline and 10 training days after. | 
| Change from baseline in Semantic Fluency | A language measure that assesses semantic fluency. | Baseline and 10 training days after. | 
| Change from baseline in Digit Span Forward | A subtest of the Wechsler Adult Intelligence Scale (WAIS-III) that is an attention measure. | Baseline and 10 training days after. | 
| Change from baseline in Digit Span Backward | A WAIS-III subtest that is a working memory measure. | Baseline and 10 training days after. | 
| Change from baseline in Letters and Numbers | A WAIS-III subtest that measures working memory. | Baseline and 10 training days after. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Intracraneal Volume (TIV) | A measure of brain volumetry. MRI sequence: structural T1-weighted MPRAGE sequence. | Baseline | 
| Brain Parenchimal Fraction (BPF) | MRI sequence: structural T1-weighted MPRAGE sequence. | Baseline | 
| Lesion Volume in white matter tissue | A brain damage volumetry measure. MRI sequence: structural T1-weighted MPRAGE sequence and T2-FLAIR sequence | Baseline | 
| Cortical Lesions | Number of brain cortical lesions. MRI Sequence: inversion recovery MRI pulse sequence (DIR). | Baseline | 
| Cortical Thickness | Brain cortical thickness measure. MRI sequence: structural T1-weighted MPRAGE sequence. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Magnetic Resonance Imaging, Neuroplasticity, Cognitive Impairment, Virtual Reality