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Dynamic Resting State Motor Network Connectivity of Neurotypical Children, the Groundwork for Network-Guided Therapy in Childhood Movement Disorders

View ORCID ProfileBethany L. Sussman, View ORCID ProfileSarah N. Wyckoff, Justin M. Fine, Jennifer Heim, Angus A. Wilfong, P. David Adelson, Michael C. Kruer, Varina L. Boerwinkle
doi: https://doi.org/10.1101/2021.11.30.470606
Bethany L. Sussman
1Division of Neurosciences, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ, 85016 USA
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  • For correspondence: bsussman@phoenixchildrens.com
Sarah N. Wyckoff
1Division of Neurosciences, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ, 85016 USA
2Department of Research, Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016 USA
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Justin M. Fine
3Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455
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Jennifer Heim
4Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016 USA
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Angus A. Wilfong
4Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016 USA
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P. David Adelson
5Division of Pediatric Neurosurgery, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016 USA
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Michael C. Kruer
4Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016 USA
6Departments of Child Health, Neurology, Genetics and Cellular & Molecular Medicine, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, 85004 USA
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Varina L. Boerwinkle
4Division of Pediatric Neurology, Barrow Neurological Institute at Phoenix Children’s Hospital, 1919 E. Thomas Rd, Phoenix, AZ 85016 USA
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Abstract

Background Normative childhood motor network resting-state fMRI effective connectivity is undefined, yet necessary for translatable dynamic resting-state network informed treatments in pediatric movement disorders.

Method Cross-spectral dynamic causal modelling of resting-state fMRI was investigated in 19 neurotypically developing 5-7-year-old children. Fully connected six-node motor network models were created for each hemisphere including primary motor cortex, striatum, subthalamic nucleus, globus pallidus internus, thalamus, and contralateral cerebellum. Parametric Empirical Bayes with exhaustive Bayesian model reduction and Bayesian modeling averaging were used to create a group model for each hemisphere; Purdue Pegboard Test (PPBT) scores for relevant hand motor behavior were also entered as a covariate at the group level to determine the brain-behavior relationship.

Results Overall, the resting-state functional MRI effective connectivity of motor cortico-basal ganglia-cerebellar networks was similar across hemispheres, with greater connectivity in the left hemisphere. The motor network effective connectivity relationships between the nodes were consistent and robust across subjects. Additionally, the PPBT score for each hand was positively correlated with the thalamus to contralateral cerebellum connection.

Discussion The normative effective connectivity from resting-state functional MRI in children largely reflect the direction of inter-nodal signal predicted by other prior modalities and was consistent and robust across subjects, with differences from these prior task-dependent modalities that likely reflect the motor rest-action state during acquisition. Effective connectivity of the motor network was correlated with motor behavior, indicating effective connectivity brain-behavior relationship has physiological meaning in the normally developing. Thus, it may be helpful for future studies in children with movement disorders, wherein comparison to normative effective connectivity will be critical for network-targeted intervention.

Impact Statement This is the first study to use pediatric resting-state functional MRI to create a normative effective connectivity model of the motor network and to also show correlation with behavior, which may have therapeutic implications for children with movement disorders.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Author Email Addresses, Bethany L. Sussman: bsussman{at}phoenixchildrens.com, Sarah N. Wyckoff: swyckoff{at}phoenixchildrens.com, Justin M. Fine: justfineneuro{at}gmail.com, Jennifer Heim: jheim{at}phoenixchildrens.com, Angus A. Wilfong: awilfong{at}phoenixchildrens.com, P. David Adelson: dadelson{at}phoenixchildrens.com, Michael C. Kruer: mkruer{at}phoenixchildrens.com, Varina L. Boerwinkle: vboerwinkle{at}phoenixchildrens.com

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 02, 2021.
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Dynamic Resting State Motor Network Connectivity of Neurotypical Children, the Groundwork for Network-Guided Therapy in Childhood Movement Disorders
Bethany L. Sussman, Sarah N. Wyckoff, Justin M. Fine, Jennifer Heim, Angus A. Wilfong, P. David Adelson, Michael C. Kruer, Varina L. Boerwinkle
bioRxiv 2021.11.30.470606; doi: https://doi.org/10.1101/2021.11.30.470606
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Dynamic Resting State Motor Network Connectivity of Neurotypical Children, the Groundwork for Network-Guided Therapy in Childhood Movement Disorders
Bethany L. Sussman, Sarah N. Wyckoff, Justin M. Fine, Jennifer Heim, Angus A. Wilfong, P. David Adelson, Michael C. Kruer, Varina L. Boerwinkle
bioRxiv 2021.11.30.470606; doi: https://doi.org/10.1101/2021.11.30.470606

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