Publications

Peixuan Zheng, Lara A Pilutti, Noah G DuBose, Robert W Motl
Cognitive dysfunction is one of the most common consequences of multiple sclerosis (MS). Recent studies have noted a high incidence of vascular comorbidity that might be associated with cognitive decline among persons with MS. However, there is a lack of evidence on vascular biomarkers (e.g., arterial stiffness indices) that are associated with cognition in MS. The current study characterized differences in vascular function between persons with MS and healthy controls, and examined the association between vascular and cognitive function in persons with MS compared with healthy controls.

• Multiple Sclerosis and Related Disorders

Peixuan Zheng, Brian M Sandroff, Robert W Motl
Physical activity (PA) represents a promising behavioral approach for managing cognitive dysfunction in multiple sclerosis (MS). However, there is a lack of information on the pattern of free-living PA intensity (e.g., step rate) and its unique association with cognition. Such information is essential for informing clinical trials in MS.

• Journal of Neurology

Robert W Motl, Brian M Sandroff, Ralph HB Benedict, Roberto Aldunate, Gary Cutter, Emily Barron
We propose a randomized controlled trial(RCT) of a Social Cognitive Theory-based(SCT), Internet-delivered behavioral intervention targeting lifestyle physical activity(LPA) for yielding improvements in cognitive processing speed(CPS), learning and memory(L/M), symptoms, and quality of life(QOL) among persons with mild multiple sclerosis(MS)-related ambulatory impairment who have impaired CPS.

• Contemporary Clinical Trials

Maria A Rocca, Paola Valsasina, Francesco Romanò, Nicolò Tedone, Maria Pia Amato, Giampaolo Brichetto, Vincenzo Daniele Boccia, Jeremy Chataway, Nancy D Chiaravalloti, Gary Cutter, Ulrik Dalgas, John DeLuca, Rachel A Farrell, Peter Feys, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Robert W Motl, Amber Salter, Brian M Sandroff, Anthony Feinstein, Massimo Filippi
Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings.

• Journal of Neurology, Neurosurgery, and Psychiatry

Michelle A Jaldin, Guilherme Moraes Balbim, Juan Pinto, Miguel Negrete, Robert W Motl, Eduardo E Bustamante, Susan Aguiñaga, Navin Kaushal, Crystal Castillo, Sonam Khanna, Amelia Brunskill, David X Marquez
Aging is associated with declines in cognition and mental health that might be ameliorated by physical activity (PA). Dance integrates multiple physical, cognitive, and social elements, and might be an avenue for improving cognition and mood. This systematic review and meta-analysis examined the effects of formal and traditional dance on cognition, depression, and anxiety in older adults.

• Medicine & Science in Sports & Exercise

Emerson Sebastião, Vitor A A A Siqueira, Jemimah O Bakare, Mahgolzahra Kamari, Robert W Motl
Studies addressing frailty in the context of multiple sclerosis (MS) are emergent. This study explores cognitive function in older adults with MS as a function of frailty status.

• International Journal of MS Care

Tobia Zanotto, Danya Pradeep Kumar, Daniel Golan, Jeffrey Wilken, Glen M Doniger, Myassar Zarif, Barbara Bumstead, Marijean Buhse, Joanna Weller, Sarah A Morrow, Iris-Katharina Penner, Laura Hancock, Thomas J Covey, Edward Ofori, Daniel S Peterson, Robert W Motl, Hans Bogaardt, Marissa Barrera, Riley Bove, Herbert Karpatkin, Jacob J Sosnoff, Mark Gudesblatt
Cognitive impairment is linked with increased risk of falls in people with multiple sclerosis (pwMS), but it is not clear whether cognitive performance may help to account for the discordance between fall-risk due to actual physiological functioning and the individual’s perception of their fall-risk. This study examined the relationship between cognitive performance and the concordance/discordance of physiological and perceived fall-risk in pwMS.

• Multiple Sclerosis and Related Disorders

Brenda Jeng, Peixuan Zheng, Robert W Motl
People with multiple sclerosis (MS) often demonstrate both cognitive and physical dysfunctions, particularly with greater age and lower physical activity levels, and there is evidence of a relationship between these outcomes (i.e., cognitive-motor coupling) in MS. To date, little is known about cognitive-motor coupling when controlling for chronological age and levels of physical activity.

• Brain Sciences

Brenda Jeng, Gary R Cutter, Robert W Motl
Cognitive impairment is prevalent, disabling, and poorly managed in multiple sclerosis (MS). Physical activity, often expressed as steps/day, has been associated with cognitive function in this population. This brief report examined the possibility of a (1) steps/day threshold associated with absence of cognitive impairment or (2) dose-response relationship between steps/day and cognitive function in MS.

• Journal of the International Neuropsychological Society

Brian M Sandroff, Robert W Motl, Roberto S Hernandez, Maria Pia Amato, Giampaolo Brichetto, Jeremy Chataway, Nancy D Chiaravalloti, Gary R Cutter, Ulrik Dalgas, John DeLuca, Rachel Farrell, Peter Feys, Massimo Filippi, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Maria A Rocca, Amber Salter, Anthony Feinstein
This study involved a secondary data analysis from the CogEx trial in progressive MS. This study first described heterogeneity of change in cognitive processing speed (CPS) across the intervention conditions and then identified possible adherence/compliance, baseline performance, and demographic/clinical variables as correlates of rehabilitation-related CPS changes.

• Neurorehabilitation and Neural Repair

Peixuan Zheng, Shane A Phillips, Jennifer Duffecy, Sydney R DeJonge, Noah G DuBose, Robert W Motl
We propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment.

• Contemporary Clinical Trials

Manuel E Hernandez, Robert W Motl, Frederick W Foley, Mary Ann Picone, Meltem Izzetoglu, Michael L Lipton, Mark Wagshul, Roee Holtzer
We investigated the levels of prefrontal cortex (PFC) activation, using oxygenated hemoglobin (HbO₂), during cognitively-demanding tasks in OAMS with lower and higher disability using functional near-infrared spectroscopy (fNIRS) to: (1) identify PFC activation differences in single task walk and cognitively-demanding tasks in OAMS with different levels of disability; and (2) evaluate if disability may moderate practice-related changes in neural efficiency in OAMS.

• Neurorehabilitation and Neural Repair

Roee Holtzer, Frederick W Foley, Robert W Motl, Mark E Wagshul, Manuel E Hernandez, Michael L Lipton, Mary Ann Picone, Meltem Izzetoglu
We examined whether brain hemodynamic responses, gait, and cognitive performances under single- and dual-task conditions predict falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) with relapsing-remitting and progressive subtypes.

• Multiple Sclerosis Journal

Michelle A Jaldin, Guilherme Moraes Balbim, Juan Pinto, Miguel Negrete, Robert W Motl, Eduardo E Bustamante, Susan Aguiñaga, Navin Kaushal, Crystal Castillo, Sonam Khanna, Amelia Brunskill, David X Marquez
Aging is associated with declines in cognition and mental health that might be ameliorated by physical activity (PA). Dance integrates multiple physical, cognitive, and social elements, and might be an avenue for improving cognition and mood. This systematic review and meta-analysis examined the effects of formal and traditional dance on cognition, depression, and anxiety in older adults.

• Medicine & Science in Sports & Medicine

Emerson Sebastião, Vitor A A A Siqueira, Jemimah O Bakare, Mahgolzahra Kamari, Robert W Motl
Studies addressing frailty in the context of multiple sclerosis (MS) are emergent. This study explores cognitive function in older adults with MS as a function of frailty status.

• International Journal of MS Care

Manuel E Hernandez, Robert W Motl, Frederick W Foley, Meltem Izzetoglu, Mark Wagshul, Roee Holtzer
This study compared older adults with progressive and relapsing-remitting MS for differences in prefrontal cortex (PFC) activation in single- and dual-task-walking and practice-related effects on neural efficiency, walking, and cognitive performances.

• Multiple Sclerosis and Related Disorders

Emma V Richardson, Robert W Motl
As the life expectancy of the multiple sclerosis (MS) community increases, new innovations and understandings of what it is to age “well” are needed. Building on a line of work exploring the meaning and experiences of aging with a disabling condition, and showing how and why people aging with MS experience this phenomenon differently, this paper progresses aging and disability literature by (re)conceptualizing what “wellbeing” means to people aging with MS, and how wellbeing may be enhanced or compromised.

• The Gerontologist

Siddharth Nayak, Mark E Wagshul, Frederick W Foley, Robert W Motl, Roee Holtzer
To assess whether resting-state functional connectivity (RSFC) brain networks are associated with gait speed in a sample of older adults with and without multiple sclerosis (MS).

• Journal of Neurology

Robert C Leavenworth, Mark E Wagshul, Robert W Motl, Frederick W Foley, Roee Holtzer
Multiple sclerosis (MS) is increasingly prevalent among older adults, and this results in the cumulative effects of aging and MS on mobility disability. The Patient-Determined Disease Steps (PDDS) is a patient-reported outcome measure of mobility disability in adults with MS, but its validity has not been established in older adults. This study validated the PDDS in older adults with MS by examining correlations with conceptually-relevant objective and subjective measures, including neuroimaging markers.

• Multiple Sclerosis and Related Disorders

Manuel E Hernandez, Robert W Motl, Frederick W Foley, Meltem Izzetoglu, Mark Wagshul, Roee Holtzer
Is gait variability higher in OAMS relative to HOA, particularly in DTW compared to STW? Furthermore, does practice result in decreased gait variability in both groups, notably under DTW compared to STW?

• Gait & Posture

Robert W Motl, Dominique Kinnett-Hopkins, Whitney Neal, Edson Flores, Dorothy Pekmezi, Victoria Flores
We propose a randomized controlled trial (RCT) that examines the effects of a remotely-delivered, cultrally-tailored exercise training program for immediate and sustained improvements in patient-reported outcomes (PROs) of walking dysfunction, symptoms, and health-related quality of life (HRQOL) among African-Americans with multiple sclerosis (MS).

• Contemporary Clinical Trials

Robert W Motl, Ariel Kidwell-Chandler, Brian M Sandroff, Lara A Pilutti, Gary R Cutter, Roberto Aldunate, Rachel E Bollaert
We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS).

• Multiple Sclerosis Journal

Robert W Motl, Ariel Kidwell-Chandler, Brian M Sandroff, Lara A Pilutti, Gary R Cutter, Roberto Aldunate, Rachel E Bollaert
This planned tertiary outcome paper examined SCT variables as mediators of the behavioral intervention effect on change in device-measured minutes/day of MVPA.

• Multiple Sclerosis and Related Disorders

Stephanie L Silveira, Robert W Motl, Katherine Froehlich-Grobe, Mitch Kay
This study is a randomized controlled trial (RCT) that examines the feasibility, acceptability, and initial efficacy of a home-based, remotely supported and supervised exercise training program that was developed using a three-step community engaged research process for persons with multiple sclerosis (MS) who are wheelchair users.

• Disability and Rehabilitation: Assistive Technology

Robert W Motl, Charles H Bombardier, Jennifer Duffecy, Brooks Hibner, Alison Wathen, Michael Carrithers, Gary Cutter
Major depressive disorder (MDD) is prevalent, yet sub-optimally treated among persons with multiple sclerosis (MS). We propose that exercise training may be a promising approach for treating depression in persons with MS who have MDD. Our primary hypothesis predicts a reduction in depression severity immediately after an exercise training intervention compared with minimal change in an attention control condition, and the reduction will be maintained during a follow-up period.

• BMC Neurology

Stephanie L Silveira, Ariel Kidwell-Chandler, Trinh L T Huynh, Katie L J Cederberg, Brenda Jeng, E Morghen Sikes, Robert W Motl
Treatment fidelity is a key component for assessing the reliability and validity of clinical trials in behavioral medicine. This manuscript reports on the outcomes of a pre-planned fidelity monitoring protocol for a Phase-III clinical trial, project Behavioral Intervention for Physical Activity in Multiple Sclerosis (BIPAMS).

• Behavioral Medicine

Robert W Motl, Brian M Sandroff, Roberto S Hernandez, Maria Pia Amato, Giampaolo Brichetto, Jeremy Chataway, Nancy D Chiaravalloti, Gary Cutter, Ulrik Dalgas, John DeLuca, Rachel Farrell, Peter Feys, Massimo Filippi, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Maria A Rocca, Amber Salter, Anthony Feinstein
This secondary, exploratory analysis of data examined the heterogeneity of VO_2peak responses and possible correlates among persons with progressive multiple sclerosis (PMS) from the CogEx trial.

• Multiple Sclerosis Journal - Experimental, Translational and Clinical

Brian M Sandroff, Robert W Motl, Roberto S Hernandez, Maria Pia Amato, Giampaolo Brichetto, Jeremy Chataway, Nancy D Chiaravalloti, Gary R Cutter, Ulrik Dalgas, John DeLuca, Rachel Farrell, Peter Feys, Massimo Filippi, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Maria A Rocca, Amber Salter, Anthony Feinstein
This study involved a secondary data analysis from the CogEx trial in progressive MS. This study first described heterogeneity of change in cognitive processing speed (CPS) across the intervention conditions and then identified possible adherence/compliance, baseline performance, and demographic/clinical variables as correlates of rehabilitation-related CPS changes.

• Neurorehabilitation and Neural Repair

Victoria A Flores, Stephanie L Silveira, David X Marquez, Dominique Kinnett-Hopkins, Augusto Miravalle, Fabian Sierra-Morales, Zulma Hernández-Peraza, Robert W Motl
Hispanic/Latino individuals with multiple sclerosis (MS) face greater disease burden and comorbidity due to limited healthcare access, underrepresentation in research, and social determinants of health (SDOH). Exercise training could manage health outcomes, but existing intervention research lacks Hispanic/Latino representation.

• Pilot and Feasibility Studies

Trinh Huynh, Brenda Jeng, Robert W Motl
This study examined if physical activity levels/sedentary time and vascular comorbidity differed between Black and White persons with MS, and further examined the associations between the variables within the two MS subpopulations.

• Disability and Health Journal

Peixuan Zheng, Lara A Pilutti, Noah G DuBose, Robert W Motl
Cognitive dysfunction is one of the most common consequences of multiple sclerosis (MS). Recent studies have noted a high incidence of vascular comorbidity that might be associated with cognitive decline among persons with MS. However, there is a lack of evidence on vascular biomarkers (e.g., arterial stiffness indices) that are associated with cognition in MS. The current study characterized differences in vascular function between persons with MS and healthy controls, and examined the association between vascular and cognitive function in persons with MS compared with healthy controls.

• Multiple Sclerosis and Related Disorders

Noah G DuBose, Sydney R DeJonge, Brenda Jeng, Robert W Motl
The research involving vascular comorbidity in people with multiple sclerosis (MS) could be advanced through investigations applying measurements of vascular function such as pulse wave velocity or flow mediated dilation as mechanistic endpoints in the study of physical comorbidity management in MS across the lifespan. We conducted a scoping review of research on vascular function parameters and outcomes in MS and developed a research agenda for future inquiry.

• Multiple Sclerosis and Related Disorders

Sydney R DeJonge, Noah G DuBose, Robert W Motl, Tracy Baynard, Bo Fernhall
This study examined the relationship between arterial stiffness and perceived fatigue in persons with MS.

• Neurological Sciences

Peixuan Zheng, Noah G DuBose, Sydney R DeJonge, Brenda Jeng, Brooks A Hibner, Robert W Motl
Vascular comorbidities are prevalent in persons with multiple sclerosis (MS), yet less is known about underlying vascular function (VF). We performed a systematic review with meta-analysis of studies that compared VF in persons with MS and healthy controls and examined factors that may moderate the difference in vascular outcomes between groups.

• Multiple Sclerosis and Related Disorders

Petra Šilić, Brenda Jeng, Robert W Motl
This study examined the associations among cardiovascular comorbidities, symptoms of depression and anxiety, and physical activity in persons with multiple sclerosis. Participants with multiple sclerosis (N = 217) completed demographic, cardiovascular comorbidity, depression, and anxiety self-report measures, and wore an accelerometer for 7 days.

• Psychology, Health & Medicine

Robert W Motl, Brian M Sandroff, Roberto S Hernandez, Maria Pia Amato, Giampaolo Brichetto, Jeremy Chataway, Nancy D Chiaravalloti, Gary Cutter, Ulrik Dalgas, John DeLuca, Rachel Farrell, Peter Feys, Massimo Filippi, Jennifer Freeman, Matilde Inglese, Cecilia Meza, Maria A Rocca, Amber Salter, Anthony Feinstein
This secondary, exploratory analysis of data examined the heterogeneity of VO2peak responses and possible correlates among persons with progressive multiple sclerosis (PMS) from the CogEx trial.

• Multiple Sclerosis Journal - Experimental, Translational and Clinical

Brooks A Hibner, Natalia S Lima, Sara R Sherman, Robert W Motl, Julio A Chirinos, Shane Phillips, Philip S Clifford, Anthony T Reder, Tracy Baynard, Bo Fernhall
Multiple sclerosis (MS) is a chronic neurological condition resulting in decreased aerobic capacity (peak VO2). The hemodynamic responses to peak exercise in MS are unknown. Further, it is unknown if the hemodynamic responses are due to disease or fitness. Therefore, the purpose was to compare hemodynamic response to peak exercise between individuals with and without MS, with similar peak VO2.

• Physiological Reports

Johannes Burtscher, Robert W. Motl, Klaus Berek, Hannelore Ehrenreich, Martin Kopp, Erich Hohenauer
Low oxygen availability (hypoxia) is a prominent but poorly understood feature in multiple sclerosis (MS). Whether hypoxia causes or drives MS pathology and symptoms or whether it is a consequence of other pathological events, such as inflammation and vascular dysfunction, is unknown. Here, we summarize the available literature on the interplay between hypoxia and both pathological and symptomatic features of MS.

• Redox Biology

C Danielle Jones, Brenda Jeng, Petra Silic, Robert W Motl
This study examined differences in the volume (i.e., minutes/day) and pattern (i.e., bouts/day or bout length) of device-measured sedentary behavior and physical activity as a function of depression symptom status in persons with MS.

• Multiple Sclerosis and Related Disorders

Petra Šilić, Robert W Motl, Jennifer Duffecy
Anxiety symptoms and anxiety disorders are prevalent and burdensome, yet poorly managed in multiple sclerosis (MS). Indeed, anxiety disorders occur in 22% of people with MS, and anxiety can negatively impact physical function, cognition, and quality of life. Currently, there are no treatment guidelines available for anxiety in MS, based on limited information regarding the efficacy of pharmacotherapy and psychotherapy. Exercise training may be a promising avenue for treatment of anxiety in MS, and this is based, in part, on a wealth of evidence in the general population of adults. This review provides an overview of anxiety and evidence from meta-analyses and systematic reviews for current treatments options in the general population and MS. We further make a case for exercise as a novel treatment approach that requires focal examination in persons with MS.

• Multiple Sclerosis and Related Disorders

Robert W Motl, Charles H Bombardier, Jennifer Duffecy, Brooks Hibner, Alison Wathen, Michael Carrithers, Gary Cutter
Major depressive disorder (MDD) is prevalent, yet sub-optimally treated among persons with multiple sclerosis (MS). We propose that exercise training may be a promising approach for treating depression in persons with MS who have MDD. Our primary hypothesis predicts a reduction in depression severity immediately after an exercise training intervention compared with minimal change in an attention control condition, and the reduction will be maintained during a follow-up period.

• BMC Neurology

Petra Šilić, Brenda Jeng, Robert W Motl
This study examined the associations among cardiovascular comorbidities, symptoms of depression and anxiety, and physical activity in persons with multiple sclerosis. Participants with multiple sclerosis (N = 217) completed demographic, cardiovascular comorbidity, depression, and anxiety self-report measures, and wore an accelerometer for 7 days. We examined the bivariate, non-parametric correlations among the variables and conducted parametric, independent samples t-tests when examining the differences in variables based on cardiovascular comorbidity status.

• Psychology, Health & Medicine

Michelle A Jaldin, Guilherme Moraes Balbim, Juan Pinto, Miguel Negrete, Robert W Motl, Eduardo E Bustamante, Susan Aguiñaga, Navin Kaushal, Crystal Castillo, Sonam Khanna, Amelia Brunskill, David X Marquez
Aging is associated with declines in cognition and mental health that might be ameliorated by physical activity (PA). Dance integrates multiple physical, cognitive, and social elements, and might be an avenue for improving cognition and mood. This systematic review and meta-analysis examined the effects of formal and traditional dance on cognition, depression, and anxiety in older adults.

• Medicine & Science in Sports & Exercise

Parisa Najafi, Robert W Motl, Mehrzad Moghadasi
Multiple sclerosis (MS) profoundly influences fatigue, depression, various physical and mental symptoms, and quality of life (QoL). Rehabilitation, including exercise training, has improved outcomes of MS, yet is often undertaken in facilities with direct supervision which present substantial barriers for accessibility and scalability. The delivery of exercise remotely via technology (tele-exercise) might overcome those barriers and improve outcomes in MS. This systematic review and meta-analysis examined the effect of tele-exercise for improving fatigue, depression, and overall health outcomes in MS patients.

• Multiple Sclerosis and Related Disorders

Olesya Iosipchuk, Glenn R Wylie, Robert W Motl, Brian M Sandroff
We sought to examine a potential neural mechanism of reduced depressive symptoms in response to aerobic treadmill walking exercise training in people with multiple sclerosis (MS). This includes a secondary analysis of depressive symptom and MRI data from an original randomized controlled trial (RCT) on exercise effects on learning and memory impairment in people with MS.

• International Journal of MS Care