Corticoreticulospinal tract neurophysiology in an arm and hand muscle in healthy and stroke subjects

Key points The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury...

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Published inThe Journal of physiology Vol. 599; no. 16; pp. 3955 - 3971
Main Authors Taga, Myriam, Charalambous, Charalambos C., Raju, Sharmila, Lin, Jing, Zhang, Yian, Stern, Elisa, Schambra, Heidi M.
Format Journal Article
LanguageEnglish
Published England Wiley Subscription Services, Inc 01.08.2021
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Summary:Key points The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury. In the present study, we assessed CReST projections to an arm and hand muscle on the same side of the body in healthy and chronic stoke subjects using transcranial magnetic stimulation. We show that CReST connection strength to the muscles differs between healthy and stroke subjects, with stronger connections to the hand than arm in healthy subjects, and stronger connections to the arm than hand in stroke subjects. These results help us better understand CReST innervation patterns in the upper limb, and may point to its role in normal motor function and motor recovery in humans. The corticoreticulospinal tract (CReST) is a major descending motor pathway in many animals, but little is known about its innervation patterns in proximal and distal upper extremity muscles in humans. The contralesional CReST furthermore reorganizes after corticospinal tract (CST) injury in animals, but it is less clear whether CReST innervation changes after stroke in humans. We thus examined CReST functional connectivity, connection strength, and modulation in an arm and hand muscle of healthy (n = 15) and chronic stroke (n = 16) subjects. We delivered transcranial magnetic stimulation to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs) from the paretic biceps (BIC) and first dorsal interosseous (FDI) muscle. We operationalized CReST functional connectivity as iMEP presence/absence, CReST projection strength as iMEP size and CReST modulation as change in iMEP size by head rotation. We found comparable CReST functional connectivity to the BICs and FDIs in both subject groups. However, the pattern of CReST connection strength to the muscles diverged between groups, with stronger connections to FDIs than BICs in healthy subjects and stronger connections to BICs than FDIs in stroke subjects. Head rotation modulated only FDI iMEPs of healthy subjects. Our findings indicate that the healthy CReST does not have a proximal innervation bias, and its strong FDI connections may have functional relevance to finger individuation. The reversed CReST innervation pattern in stroke subjects confirms its reorganization after CST injury, and its strong BIC connections may indicate upregulation for particular upper extremity muscles or their functional actions. Key points The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury. In the present study, we assessed CReST projections to an arm and hand muscle on the same side of the body in healthy and chronic stoke subjects using transcranial magnetic stimulation. We show that CReST connection strength to the muscles differs between healthy and stroke subjects, with stronger connections to the hand than arm in healthy subjects, and stronger connections to the arm than hand in stroke subjects. These results help us better understand CReST innervation patterns in the upper limb, and may point to its role in normal motor function and motor recovery in humans.
Bibliography:These authors contributed equally to this work.
The peer review history is available in the Supporting Information section of this article
https://doi.org/10.1113/JP281681#support‐information‐section
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Edited by: Richard Carson & Charlotte Stagg
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Sharmila Raju, MS, Chicago Medical School, Rosalind Franklin University, 3333 Green Bay Rd, North Chicago, IL 60064
Elisa Stern, MRes, Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510
Yian Zhang, PhD, Division of Biostatistics, Department of Population Health, School of Medicine, New York University, New York, United States, 180 Madison Avenue, 2nd Floor, Cubicle 2-35C, NY 10016
Charalambos C. Charalambous, PhD, Department of Basic and Clinical Sciences, and Center for Neuroscience and Integrative Brain Research (CENIBRE), Medical School, University of Nicosia, Nicosia, Cyprus. 1 28th October Ave, Block D, Room 309, CY-2414, Nicosia, Cyprus
Jing Lin, MD, NYU Grossman School of Medicine, Physical Medicine & Rehabilitation Residency Program, 240 east 38th street, NY, NY 10016
Shared authorship
Myriam Taga, PhD, Department of Neurology, NYU Langone, School of Medicine, New York, United States. NYU Langone Health, 222 E 41st Street, 10th Floor, New York, NY 10017
Author’s contribution: HMS provided the funding and resources for the data acquisition and analysis and supervised the study. HMS, CCC, and SR led project administration. HMS and CCC developed the methodology of the study. CCC, SR, JL, ES performed the experiment. HMS, CCC, and MT were responsible for the conception and experimental design of the study. HMS, CCC, MT, SR, JL, and ES were responsible for data curation. CCC and MT developed codes for data acquisition and analysis. HMS, CCC, MT, and YZ analyzed the data. HMS, CCC, and MT validated the results. HMS, CCC, MT, and SR visualized the data. HMS and MT drafted the article. All authors revised the article critically for important intellectual content. All authors have approved the final version of the manuscript and greed to be accountable for all aspects of the work. All persons designated authors qualify for authorship, and all those who qualify for authorship are listed.
ISSN:0022-3751
1469-7793
DOI:10.1113/JP281681