MRI findings may suggest physical therapy strategies to help MS patients walk and balance better

Brett Fling, Ph.D.

Colorado State University

Funded in September, 2017: $200000 for 3 years
LAY SUMMARY . ABSTRACT .

LAY SUMMARY

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MRI findings may suggest physical therapy strategies to help MS patients walk and balance better

This MRI study of the brain’s bundle of connections that link the left and right hemispheres may provide a basis for designing better physical therapy strategies to help people with MS improve their walking and balance abilities. Problems with walking and balance occur in about 50 percent of MS patients who note apparent differences in the strength and functioning in one leg compared to the other within 18 years following diagnosis. These problems may be associated, the investigators hypothesize, with structural impairments in the fibers that compose this bundle of connections (the “corpus callosum”) that connect the two brain hemispheres. Those impairments may impede communication between the two hemispheres, which must be precisely coordinated in terms of space and time for effectively walking and maintaining balance.

When precisely coordinated, the movement of one leg has an inhibitory effect on the other, reducing the other leg’s unintended movements. If this coordination is disrupted in MS, it might explain why patients develop problems walking and maintaining balance. Investigators will examine structural and functional aspects between the brain’s two hemispheres in 30 people with MS and 30 healthy participants. They will assess: 1) structural connections between the brain’s two hemispheres using MRI imaging; 2) coordination of each person’s two legs while walking and keeping their balance; 3) the inhibitory capacity between the right and left hemispheres by using non-invasive transcranial magnetic stimulation, which briefly suppresses muscle activity as each participant contracts one leg; and 4) mobility, balance control, and leg strength and functioning in the MS patients as they wear wireless sensors that quantify their movement.

Significance : Identifying neural biomarkers of reduced inhibitory control essential for walking and maintaining balance could lead to new means to increase inhibitory control in MS patients and conceivably also in patients with Parkinson’s disease or stroke. More immediately, the findings could improve physical therapy strategies, such as using a “split-belt” treadmill in which a different walking speed is presented to each leg to induce adaptation.    

ABSTRACT

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MRI findings may suggest physical therapy strategies to help MS patients walk and balance better

Impaired walking ability is common in persons with MS (PwMS), with over 50% of PwMS requiring assistance within 18 years of diagnosis 1. Persons with multiple sclerosis (PwMS) often report significant asymmetries in strength and function between the legs. Reduced coordination during gait (i.e. increased gait asymmetry) is associated with increased metabolic cost, postural instability, falls and reduced quality of life in those living with Parkinson’s disease or following a stroke 9-11, but has yet to be adequately quantified in PwMS. Typically, such asymmetries arise from habitual tendencies, specific training programs, unilateral injuries, or pathology such as a stroke, spinal cord injury, or traumatic brain injury. The neural mechanisms underlying mobility asymmetries in PwMS are poorly understood. Transcallosal communication via the corpus callosum plays a key role in the production of integrated motor behavior to generate appropriate, coordinated motor responses on both sides of the body. While each primary motor cortex has dense projections to the contralateral muscles controlling movement, the two cortices are also highly interconnected via the corpus callosum allowing for interhemispheric transfer of information. For motor behaviors that require precise temporal and spatial coordination between the two sides of the body (e.g. walking, postural control of balance, typing), movement of one limb has an overall inhibitory effect on the ipsilateral motor cortex13-15. Similar to results observed in healthy aging, reduced structural connectivity of the corpus callosum is common in PwMS16,17. In addition, a small but burgeoning body of literature demonstrates PwMS also exhibit reduced interhemispheric inhibition between the primary motor cortices (M1) compared to age-matched controls 18, and this reduced inhibition is directly related to worse clinical function as measured by the expanded disability status scale, specifically designed to assess disease severity in PwMS 19. It remains to be tested how these changes in transcallosal communication contribute to lower limb asymmetries and the resultant declines in mobility for PwMS; however, our recent data suggests that altered transcallosal communication subsequent to reductions in corpus callosum structural integrity plays a substantial role. Our overarching hypothesis is that PwMS experience reduced corpus callosum structural connectivity which leads to reduced interhemispheric inhibition, and thus motor overflow between the sensorimotor hemispheres resulting in an impaired ability to precisely and accurately coordinate bilateral muscle activity and movement. The aims of the proposed project are to determine: 1) MRI-derived measures of transcallosal white matter quality and quantity levels of interhemispheric inhibition and excitation, 2) bilateral gait coordination, and 3) limb loading asymmetry during static and dynamic balance tasks in 30 PwMS and 30 age- and gender-matched controls. We hypothesize that PwMS will have quality and quantity of white matter fiber tracts connecting the right and left sensorimotor cortices of the brain (i.e. transcallosal tracts) as well as reduced transcallosal inhibition. Further we hypothesis that PwMS will exhibit reduced gait coordination coupled with greater limb-loading asymmetries during static and dynamic balance tasks compared to age- and gender-matched controls. Finally, we hypothesize that reduced transcallosal fiber tracts and reduced transcallosal inhibition will both be significantly associated with poorer gait coordination in healthy participants and PwMS. This would indicate that those who maintain the ability to inhibit the ipsilateral motor cortex may more effectively perform tasks that require coordinating asymmetric, bilateral movements like gait. Improving our understanding of how the nervous system perceives and adapts to gait asymmetry will help to optimize rehabilitation and will provide fundamental insights in the persistence of gait asymmetry in populations with neurological and/or musculoskeletal disorders including PwMS, stroke, and Parkinson’s disease. These results will provide translational neural biomarkers for future rehabilitation studies with a focus on addressing the millions of individuals who experience function-limiting, lower extremity asymmetries during gait, with a specific emphasis on a novel rehabilitation program using a split-belt treadmill where different walking speeds can be presented to each leg inducing significant gait adaptation

INVESTIGATOR BIOGRAPHIES

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Brett Fling, Ph.D.

Dr. Fling received his Master’s degree from the University of Massachusetts and his PhD from the University of Michigan with an emphasis in Kinesiology and Neuroscience. Dr. Fling completed postdoctoral fellowships at the University of California – Irvine and the Oregon Health & Science University (OHSU) prior to joining the Neurology faculty at OHSU in Portland, OR. Beginning in 2016, Dr. Fling is now the Director of the Sensorimotor Neuroimaging Laboratory in the Department of Health and Exercise Science at Colorado State University where his research program is focused on understanding how the nervous system, particularly the brain, controls our bodies’ movements. The Sensorimotor Neuroimaging Laboratory uses several brain imaging technologies like magnetic resonance imaging (MRI) transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to identify differences in structure and function of the brain. These measures of neural structure and function and then related metrics of gait and balance impairments with a long-term focus on developing and refining movement rehabilitation programs for those with neurologic disease or injury such as multiple sclerosis, Parkinson’s disease, and traumatic brain injury.

KEYWORDS


Anatomy: Corpus collosum
Motor cortex
Conditions: Multiple Sclerosis
Function: Brain and behavior
Lateralization of the brain
Left hemisphere/right hemisphere
Technology: Diffusion tensor imaging
MRI
Transcranial Magnetic Stimulation