Behavior and Activity Monitoring in MS

The investigators propose to conduct a randomized 6-month intervention study comparing cognitive functioning in individuals with relapsing-remitting multiple sclerosis assigned to either a physical activity or an active water-intake control group. Individuals will complete pre-, mid- and post-assessments of cognitive, physical, and behavioral functioning.

Interventions to increase physical activity through aerobic exercise are some of the only known treatment options to improve domains of cognition such as executive function. While increased physical activity is associated with preserved cortical functioning during exogenous executive functioning tasks in older adults, little is known about the relationship between physical activity and executive functioning in multiple sclerosis. Thus, the investigators propose to conduct a randomized 6-month accelerometry-based intervention designed to increase overall physical activity in sedentary relapsing-remitting multiple sclerosis with known cognitive challenges. The overall objective is to determine how a 6-month activity tracking intervention impacts the behavioral, neural and mechanistic associations between physical activity and cognitive functioning. All individuals who contact the Clinical Neuroscience Laboratory (CNL) with interest in this study will undergo a phone/online screening assessing inclusion/exclusion criteria. Those participants meeting I/E criteria will be invited to the lab for 2 pre-assessment sessions, one session at midpoint, and 2 post-assessment sessions at the completion of the 6 month intervention. Participants will also be asked to complete a number of online questionnaires following the first assessment session. The two pre-assessments will involve a through measure of cognitive functioning, both through the use of neuropsychological batteries and neuroimaging, and inflammatory markers through collection of a blood sample. Following the pre-assessment sessions, conducted by blind personnel, participants will be randomized to one of the two groups. Participants will be asked to self-monitor their assigned health behavior with the aid of a behavioral tracker (accelerometer or smart water bottle). Via a mobile application designed by the laboratory, participants will receive daily and weekly summaries of their health behavior progress, and motivational materials to encourage goal attainment. The 6-month intervention will involve minimal contact from study coordinators. Participants who do not adhere to study goals will be contacted by a study coordinator via phone who will use motivational interviewing to promote behavior change. Following the 6-month intervention the 2 assessment sessions will be repeated to obtain post-intervention data for comparison.

Multiple Sclerosis, Sclerosis, Demyelinating Autoimmune Diseases, Central Nervous System, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Demyelinating Diseases, Immune System Diseases, Physical Activity, Walking, Hydration, Lifestyle Intervention, Health Behavior Tracking, Inflammatory Biomarkers, Neurodegenerative Disease

Participants will track their physical activity in steps using an accelerometer for a period of 6 months. Participants will monitor their overall step-count using the accelerometer, and daily and weekly summaries of their progress provided by the experimenters.

Participants will track their water-intake using a smart water bottle for a period of 6 months. Participants will monitor their overall water consumption using a smart water bottle, and daily and weekly summaries of their progress provided by the experimenters.

The step tracking intervention is designed to increase physical activity through the use of self-monitoring and brief motivational materials. The motivational materials will be delivered at various points during the intervention. Participants are not required to access and read these materials, however, the hope is these materials will aid in study and goal adherence. Engagement in the intervention will be tracked by the experimenters using the behavioral data gathered by the tracker.

The water tracking intervention is designed to increase water intake, to a healthy level, through the use of self-monitoring and brief motivational materials.The motivational materials will be delivered at various points during the intervention. Participants are not required to access and read these materials, however, the hope is these materials will aid in study and goal adherence. Engagement in the intervention will be tracked by the experimenters using the behavioral data gathered by the tracker.

Change in a latent factor of working memory/processing speed will be examined from pre to post intervention. This latent factor will be created using baseline performance on measures from the Minimal Assessment of Cognitive Functioning in Multiple Sclerosis battery (MACFIMS), the NIH Toolbox Cognition Battery (NIHTB-CB), and the processing speed and working memory measures from the Wechsler Adult Intelligence Scale (WAIS-IV) before, during (at midpoint), and after the intervention. Higher scores on this factor represent better working memory/processing speed performance. Investigators hypothesize changes in cognitive performance, specifically in the domains of working memory and processing speed.

Before and after the intervention, participants will undergo a brain imaging scan using functional Magnetic Resonance Imaging (fMRI) technology. Network strength in the working memory connectome during the NBack task will be the primary fMRI-based neuroimaging measure. Higher network strength in the working memory connectome represent greater connections between brain edges associated with high working memory performance. Participants in the physical activity group will show increased network strength in a connectome-based model of working memory performance.

Before and after the intervention, participants will undergo a brain imaging scan using functional Magnetic Resonance Imaging (fMRI) technology. Network strength in the processing speed neuromaker during the Symbol Digit Modalities Test will be the outcome variable. Higher network strength in the processing speed neuromarker represent greater connections between brain edges associated with high processing speed performance. Participants in the physical activity group will show increased network strength in this neuromarker of processing speed.

Participants will be administered Beck Depression Inventory-II before, at mid-point, and after the intervention. This measure assesses self-reported depressive symptoms with a range of 0-63 with higher scores characterizing higher endorsement of depressive symptoms. Changes in scores will indicate effects of the intervention on symptoms of depression.

Participants will be administered the Penn State Worry Questionnaire before, at mid-point and after the intervention. This measure assesses self-reported worry symptoms with a range of 16-80. High scores on this measure represent higher levels of chronic worrying. Change on this measure will be assessed to determine the impact of the intervention on symptoms of worry.

Participants will be administered the Perceived Stress Scale before, at mid-point and after the intervention. This measure assesses perceived stress with a range of 0-40. High scores on the perceived stress scale represent higher levels of stress. Change on this measure will indicate impact of the intervention on symptoms of stress.

Participants will be administered the Satisfaction with Life Scale and the World Health Organization Quality of Life Scale before, at mid-point, and after the intervention. Standardized scores for the two measures will be merged to create a composite score for quality of life. High scores on this composite measure would represent higher quality of life. Differences in the composite score of quality of life will reveal changes in quality of life as a function of the intervention.

Participants will be administered the Pittsburgh Sleep Quality Index before, at mid-point, and after the intervention. This measure assesses sleep quality with a range of 0-21. Higher score on this measure represents greater difficulty with sleep. Score changes on this measure will indicate changes in sleep quality as a function of the intervention.

Participants will be administered the Modified Fatigue Impact Scale before, at mid-point and after the intervention. This measure assesses self-reported fatigue with a range of 0-84. High scores on this measure represent higher levels of experienced fatigue. Differences in scores on this measure will indicate changes in fatigue as a function of the intervention.

Inclusion Criteria: Clinically definite diagnosis of Relapsing-Remitting Multiple Sclerosis Score higher than 23 on the Mini-Mental Status Examination (MMSE) Expanded Disability Status Scale (EDSS) under 5.5 Right-handed Exclusion Criteria: Clinically isolated syndrome or progressive MS subtype Presence of any other neurological disorders Presence of psychiatric disorder diagnosed by a licensed mental health provider in the last two years Clinically definite relapse or use of high dose corticosteroids within the last 30 days Recreational drug use in the last 6 months Without access to a smart phone or no access to the internet Current use of accelerometer, pedometer, and/or physical activity monitoring equipment Presence of ferromagnetic implanted devices or self-reported claustrophobia

Manglani HR, Fountain-Zaragoza S, Shankar A, Nicholas JA, Prakash RS. Employing Connectome-Based Models to Predict Working Memory in Multiple Sclerosis. Brain Connect. 2022 Aug;12(6):502-514. doi: 10.1089/brain.2021.0037. Epub 2021 Sep 28.