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Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions
Ryan T Muir1, Benjamin Lam1, Kie Honjo1
1From the L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre (R.T.M., B.L., K.H., R.D.H., A.A.M., F.-Q.G., J.R., C.J.M.S., A.G., J.Z., S.E.B.), Heart and Stroke Foundation Centre for Stroke Recovery, Sunnybrook Health Sciences Centre (R.T.M., B.L., K.H., R.D.H., A.A.M., F.-Q.G., J.R., C.J.M.S., A.G., J.Z., E.G., S.E.B.), Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute (R.T.M., B.L., K.H., R.D.H., A.A.M., F.-Q.G., J.R., C.J.M.S., A.G., J.Z., S.J.G., E.G., D.T.S., S.E.B.), Department of Medicine, Division of Neurology (R.T.M., B.L., K.H., R.D.H., A.A.M., F.Q.G., J.R., C.J.M.S., A.G., J.Z., E.G., N.J.L , D.T.S., S.E.B.), Department of Medical Biophysics (S.J.G.), Rotman Research Institute, Baycrest (D.T.S., S.E.B.), and Department of Research Design and Biostatistics, Sunnybrook Health Sciences Centre (A.K.), University of Toronto, Toronto, ON, Canada; Departments of Radiology, Neurosurgery, and Bioengineering (X.J.Z.), and Department of Clinical Neuropsychology (N.R., D.L.N.), College of Medicine at Chicago, University of Illinois; Hauenstein Neuroscience Center, Saint Mary's Health Care, Grand Rapids, MI (N.R., D.L.N.); Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada (N.J.L.); Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea (B.-C.L., Y.K.); Department of Psychology, Hallym University, Chuncheon, South Korea (Y.K.); and Heart and Stroke Foundation Canadian Partnership for Stroke Recovery (K.H., S.E.B.).
Background And Purpose:
Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates.
Methods:
One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute-subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented.
Results:
Multiple linear regression analyses were completed. Although larger infarcts (β=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (β=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (β=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity.
Conclusions:
In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.
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