Cognitive Dysfunction in MS: Using Altered Brain Oscillation to Link Molecular Mechanisms With Clinical Outcomes

Study Overview
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Brief Summary
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Up to 65% of patients with multiple sclerosis (MS) experience cognitive dysfunction. Diminution of mental capacity has a pervasive and profound impact on their quality of life. Subtle changes in white matter predict cognitive changes in these patients but how this disrupts brain function remains unclear. Development of effective therapeutics to restore normal cognition hinges on elucidating these functional changes. The investigators seek to uncover the patho-physiological basis for cognitive decline in MS. The investigators hypothesize that cognitive decline originates from disrupted gamma oscillations and that gamma oscillations are disrupted by molecular changes triggered by demyelination.

Official Title
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Cognitive Dysfunction in MS: Using Altered Brain Oscillation to Link Molecular Mechanisms With Clinical Outcomes

Conditions
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Pediatric Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (*applicable to controls): Must be between 6 and 17 years and 11 months of age*; Have a diagnosis of MS according to the revised McDonald diagnostic criteria and/or International Pediatric MS Study Group criteria; Has English language knowledge at the level needed to complete clinical questionnaires (4th grade level).* Exclusion Criteria (*applicable to controls): Neurological comorbidity.*; Relapses or requires treatment with steroids within 30 days from enrollment; Is pregnant at the time of enrollment.*; Has any metal parts in their body (i.e. Cochlear (ear) implant, metal braces (dental fillings are o.k.).*; Is younger than 6 years of age.*; Is older than 18 years of age.*; Has prior history of traumatic brain injury, neurological disorder, cerebral palsy, developmental delay or learning disability.*; Requires sedation for brain scanning.*; Is claustrophobic, as brain scanning requires children to enter a tunnel in the MRI machine.*

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 7 pediatric-onset multiple sclerosis<br> | |
| 7 non-patient healthy volunteers<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuronal responses during simple and choice reaction time tasks | Video-based eye tracking in the MEG | 60 minutes | 
| MRI scans of the brain, including Diffusion Tensor Imagine (DTI) |  | 90 minutes | 
| Neurocognitive Testing | Penn Computerized Neurocognitive Battery | 90 minutes | 
| Neurological Exam - Standard physical exam performed by the neurologist to determine the Expanded Disability Status Scale (EDSS) score. |  | 20 minutes | 
| Clinical Interview | Series of questions about the participant's demographic and clinical information including, current and past health, family history, and medications. | 10 minutes |