Related Experiment Video
Updated: Sep 23, 2025
Electroencephalography Network Indices as Biomarkers of Upper Limb Impairment in Chronic Stroke
Published on: July 14, 2023
Observational Study of Neuroimaging Biomarkers of Severe Upper Limb Impairment After Stroke
Kathryn S Hayward1, Jennifer K Ferris2, Keith R Lohse2
1From the Departments of Physiotherapy (K.S.H.), Medicine and Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Heidelberg, Victoria, Australia; Rehabilitation Sciences Graduate Research Program (J.K.F., L.A.B.), University of British Columbia, Vancouver, British Columbia, Canada; Physical Therapy and Neurology (K.R.L.), Washington University School of Medicine in Saint Louis, MO; Division of Physical Therapy (M.R.B.), Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, GA; School of Health Sciences (A.B.), Department of Physical Therapy, College of St. Scholastica, Duluth, MN; Department of Allied Health Sciences (J.M.C.), University of North Carolina at Chapel Hill, NC; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles, California; Department of Clinical Neurosciences (S.P.D., S.E.F.), Cumming School of Medicine, University of Calgary, Alberta, Canada; School of Kinesiology (R.L.H.), University of Minnesota, Minneapolis; Chan Division of Occupational Science and Occupational Therapy (S.-L.L.), Biokinesiology and Physical Therapy, Biomedical Engineering, and Neurology, USC Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles; Université de Montréal (J.L.N.), École de Kinésiologie et des Sciences de l'activité Physique, Faculté de Médecine, and Centre de recherche de l'institut universitaire de gériatrie de Montréal, Quebec, Canada; and Physical Therapy Program (J.C.S.), Department of Exercise Science, University of South Carolina, Columbia. kate.hayward@unimelb.edu.au.
Background And Objectives:
It is difficult to predict poststroke outcome for individuals with severe motor impairment because both clinical tests and corticospinal tract (CST) microstructure may not reliably indicate severe motor impairment. Here, we test whether imaging biomarkers beyond the CST relate to severe upper limb (UL) impairment poststroke by evaluating white matter microstructure in the corpus callosum (CC). In an international, multisite hypothesis-generating observational study, we determined if (1) CST asymmetry index (CST-AI) can differentiate between individuals with mild-moderate and severe UL impairment and (2) CC biomarkers relate to UL impairment within individuals with severe impairment poststroke. We hypothesized that CST-AI would differentiate between mild-moderate and severe impairment, but CC microstructure would relate to motor outcome for individuals with severe UL impairment.
Methods:
Seven cohorts with individual diffusion imaging and motor impairment (Fugl-Meyer Upper Limb) data were pooled. Hand-drawn regions-of-interest were used to seed probabilistic tractography for CST (ipsilesional/contralesional) and CC (prefrontal/premotor/motor/sensory/posterior) tracts. Our main imaging measure was mean fractional anisotropy. Linear mixed-effects regression explored relationships between candidate biomarkers and motor impairment, controlling for observations nested within cohorts, as well as age, sex, time poststroke, and lesion volume.
Results:
Data from 110 individuals (30 with mild-moderate and 80 with severe motor impairment) were included. In the full sample, greater CST-AI (i.e., lower fractional anisotropy in the ipsilesional hemisphere, p < 0.001) and larger lesion volume (p = 0.139) were negatively related to impairment. In the severe subgroup, CST-AI was not reliably associated with impairment across models. Instead, lesion volume and CC microstructure explained impairment in the severe group beyond CST-AI (p's < 0.010).
Discussion:
Within a large cohort of individuals with severe UL impairment, CC microstructure related to motor outcome poststroke. Our findings demonstrate that CST microstructure does relate to UL outcome across the full range of motor impairment but was not reliably associated within the severe subgroup. Therefore, CC microstructure may provide a promising biomarker for severe UL outcome poststroke, which may advance our ability to predict recovery in individuals with severe motor impairment after stroke.
