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Bridging the Callosal Gap in Gait:
Sutton B. Richmond1, Clayton W. Swanson1, Tyler T. Whittier1, Daniel S. Peterson3, & Brett W. Fling1,2
1Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA
2Molecular, Cellular, & Integrative Neuroscience Program, Colorado State University, Fort Collins, CO, USA
3College of Human Solutions, Arizona State University, Phoenix, AZ, USA
Background & Purpose
Multiple sclerosis is a neurodegenerative disease that affects more than 1 million
individuals in the United States alone1. Approximately 75% of people with multiple
sclerosis (PwMS) experience reduced balance and increased risk of falls during the
duration of their disease, making assessments of mobility and balance imperative2. An
essential part of mobility is bilateral control of the legs during locomotion, i.e.
coordinated patterns of the lower limbs produce locomotive actions with each leg
operating in its own spatial and temporal pattern3. The corpus callosum, the anatomical
structure bridging the two hemispheres of the brain, is integral for the coordination of
such complex, coordinated movements4. Bilateral movement control and corpus
callosum structural integrity are substantially compromised in PwMS5.
Purpose: The aim of this project was to assess MRI-derived measures of transcallosal
sensorimotor fiber tract microstructural integrity (via diffusion imaging) and identify
the relation to gait coordination using novel methods of ecologically-valid mobility
assessments in PwMS and age/sex-matched neurotypical adults.
Neurotypical adults (4 male and 12 females; 43 ± 17 years) and PwMS (9 males and 15 females; 49
± 12 years) underwent a two-minute walk at a self-selected speed. Lower limb asymmetries were
quantified via the Phase Coordination Index (PCI), a comprehensive metric to evaluate bipedal
coordination by assessing both the accuracy and consistency of phase generation during
locomotion6. White matter microstructure of transcallosal sensorimotor tracts connecting
homologous regions of the sensorimotor cortices was evaluated with diffusion tensor imaging.
Radial diffusivity (RD), an indirect marker of myelination, was utilized as the primary outcome
measure of white matter microstructural integrity. Additionally, fractional anisotropy (FA), a
measure that quantifies white matter integrity on a voxel by voxel basis and apparent fiber density
(AFD), a measure that estimates the intra-axonal volume fraction within each of the single fiber
bundles, were quantified.
Data Analysis
PCI was derived from six wireless, inertial sensors (Opals, APDM, Portland, OR) sampled at 128 Hz (Fig. 1). An independent sample T-
test was used to assess group differences in PCI. A 2 x 8 RMANOVA was used to identify differences in transcallosal sensorimotor fiber
bundles with fiber tract as the within-subject main effect and group as the between-subject main effect. Associations between fiber tract
integrity and gait coordination was identified with Pearson’s correlations between PCI and each of the eight sensorimotor fiber bundles.
Figure 1: Opal inertial sensor
set-up during the two-minute
walk test. Sensors were placed
on the sternum, on the lumbar,
each wrist, and on each foot.
Conclusion
In this preliminary analysis of an ongoing data collection, results indicate that PwMS demonstrate decreased bilateral coordination during over-ground walking and
poorer transcallosal white matter microstructural integrity of sensorimotor fiber tracts in comparison to an age and gender matched neurotypical cohort. PwMS walked
with significantly poorer consistency and accuracy in astep by step analysis of the gait cycle compared to their neurotypical counterparts. Additionally, fiber tract
integrity of transcallosal white matter connections between primary sensorimotor cortical regions appear to be associated with gait coordination during self-paced
over-ground walking in clinical population with specific callosal impairment, but not in neurotypical controls. This on-going project emphasizes the importance of
transcallosal communication in those with known deficits of this neuroanatomical structure and provides a foundation for future neurorehabilitation approaches.
References
1. Wallin, M.T., et al., Neurology, 92 (10), 2019.
2. Attya, A., et al., The Egyptian Journal of Neurology, Psychiatry, and Neurosurgery, 55 (1), 2019.
3. Mirelman, A., et al., Handb Clin Neurol, 159, 119-134, 2018.
4. Serbruyns, L., et al., Brain Struct Funct, 220 (1), 273-290, 2015.
5. Bonzano, L., et al., J Neurosci, 28 (12), 3227-3233, 2008.
6. Plotnik, M., N. Giladi, and J.M. Hausdorff, Exp Brain Res, 181 (4), 561-570, 2007.
7. Ruddy, K.L., A. Leemans, and R.G. Carson, Brain Struct Funct, 222 (3), 1243-1252, 2017.
Neurotypical
PCI
Consistency !"#$%&Accuracy !"#'()&
1.82*
0.019* 1.80*
Multiple Sclerosis
PCI
Consistency !"#$%&Accuracy !"#'()&
3.33*
0.030* 3.30*
Fiber
Bundle
Neurotypical PwMS
RD*
FA
†
AFD
RD*
FA
†
AFD
CMA
4.4 x 10
-
4
0.43
0.58
4.9 x 10
-
4
0.40
0.56
Pre
-
SMA
4.0 x 10
-
4
0.51
0.70
4.5 x 10
-
4
0.48
0.68
SMA-
Proper
3.9 x 10
-
4
0.52
0.74
4.4 x 10
-
4
0.48
0.72
PMd
4.1 x 10
-
4
0.51
0.47
4.6 x 10
-
4
0.48
0.38
PMv
4.8 x 10
-
4
0.41
0.56
5.0 x 10
-
4
0.41
0.57
M1a
4.4 x 10
-
4
0.48
0.69
4.9 x 10
-
4
0.43
0.63
M1p
4.8 x 10
-
4
0.38
0.33
5.3 x 10
-
4
0.36
0.29
S1
4.6 x 10
-
4
0.44
0.58
5.0 x 10
-
4
0.39
0.52
Fiber
Bundle
Neurotypical
PwMS
rprp
CMA
- 0.01
0.52 0.12 0.30
Pre
-
SMA
- 0.38
0.93 0.12 0.29
SMA-
Proper
- 0.06
0.59 0.27 0.10
PMd
- 0.09
0.63 0.19 0.18
PMv 0.26 0.16 0.24 0.13
M1a
- 0.04
0.56 0.30 0.07
M1p 0.32 0.12 0.11 0.30
S1
- 0.07
0.60 0.17 0.21
*significance between PwMS & neurotypical cohorts in RD value; p-value = 0.002.
†significance between PwMS & neurotypical cohorts in FA value; p-value = 0.006.
Table 1: Neuroimaging Values Table 2:
Pearson’s (r) Correlations
M1p
M1a
PMv
SMA-proper
PMd
CMA
pre-SMA
S1
Figure 4: Pictorial description of the two-minute
instrumented walk each participant underwent, with
inertial-sensors.
Figure 5: Bilateral coordination quantified via the mean
PCI, including the accuracy and consistency of the gait
cycle phase generation of the neurotypical adult
participants (A) and PwMS (C). Representative phase
generation diagrams of a neurotypical adult (B) and a
person with MS (D). * p-value < 0.05 between PwMS
& neurotypical adult.
A
B
C
D
B
Poorer Coordination
Poorer Tract Microstructure
Methods
Figure 3: Scatterplot of
Phase Coordination Index
and microstructural integrity
of the Primary Motor
Cortices (M1a) transcallosal
sensorimotor fiber bundle
(seen in Figure 2).
Figure 2: Display of the sensorimotor transcallosal fiber bundles7(top), diagram of the overall study hypothesis (middle), and differences in gait asymmetries exhibited between young adults and PwMS (bottom).
P2-H-70
Acknowledgements
Investigators received grant funding from the Dana Foundation and the National Multiple Sclerosis
Society (PP-1708-29077) that facilitated the research presented in this poster.
