David A Cunningham1, Andre Machado2, Daniel Janini3, Nicole Varnerin3, Corin Bonnett3, Guang Yue4, Stephen Jones5, Mark Lowe5, Erik Beall5, Ken Sakaie5, Ela B Plow6. 1. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; School of Biomedical Sciences, Kent State University, Kent, OH. 2. Center for Neurological Restoration, Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH. 3. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH. 4. Human Performance and Engineering Laboratory, Kessler Foundation Research Center, West Orange, NJ. 5. Imaging Institute, Cleveland Clinic, Cleveland, OH. 6. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; Center for Neurological Restoration, Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH; Department of Physical Medicine and Rehabilitation, Neurological Institute, Cleveland Clinic, Cleveland, OH. Electronic address: plowe2@ccf.org.
Abstract
OBJECTIVE: To determine how interhemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance [fMRI], diffusion-tensor imaging [DTI]) and how these metrics of balance are associated with clinical measures of upper-limb function and disability. DESIGN: Cross sectional. SETTING: Laboratory. PARTICIPANTS: Patients with chronic stroke (N = 10; age, 63 ± 9 y) in a population-based sample with unilateral upper-limb paresis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interhemispheric balance was measured with TMS, fMRI, and DTI. TMS defined interhemispheric differences in the recruitment of corticospinal output, size of the corticomotor output maps, and degree of mutual transcallosal inhibition that they exerted on one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor cortex (M1), premotor cortex (PMC), and supplementary motor cortex (SMA). DTI was used to define interhemispheric differences in the integrity of the corticospinal tracts projecting from the M1. Clinical outcomes tested function (upper extremity Fugl-Meyer [UEFM]) and perceived disability in the use of the paretic hand (Motor Activity Log [MAL] amount score). RESULTS: Interhemispheric balance assessed with TMS relates differently to fMRI and DTI. Patients with high fMRI lateralization to the ipsilesional hemisphere possessed stronger ipsilesional corticomotor output maps (M1: r = .831, P = .006; PMC: r = .797, P = .01) and better balance of mutual transcallosal inhibition (r = .810, P = .015). Conversely, we found that patients with less integrity of the corticospinal tracts in the ipsilesional hemisphere show greater corticospinal output of homologous tracts in the contralesional hemisphere (r = .850, P = .004). However, an imbalance in integrity and output do not relate to transcallosal inhibition. Clinically, although patients with less integrity of corticospinal tracts from the ipsilesional hemisphere showed worse impairments (UEFM) (r = -.768, P = .016), those with low fMRI lateralization to the ipsilesional hemisphere had greater perception of disability (MAL amount score) (M1: r = .883, P = .006; PMC: r = .817, P = .007; SMA: r = .633, P = .062). CONCLUSIONS: In patients with chronic motor deficits of the upper limb, fMRI may serve to mark perceived disability and transcallosal influence between hemispheres. DTI-based integrity of the corticospinal tracts, however, may be useful in categorizing the range of functional impairments of the upper limb. Further, in patients with extensive corticospinal damage, DTI may help infer the role of the contralesional hemisphere in recovery.
OBJECTIVE: To determine how interhemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance [fMRI], diffusion-tensor imaging [DTI]) and how these metrics of balance are associated with clinical measures of upper-limb function and disability. DESIGN: Cross sectional. SETTING: Laboratory. PARTICIPANTS: Patients with chronic stroke (N = 10; age, 63 ± 9 y) in a population-based sample with unilateral upper-limb paresis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interhemispheric balance was measured with TMS, fMRI, and DTI. TMS defined interhemispheric differences in the recruitment of corticospinal output, size of the corticomotor output maps, and degree of mutual transcallosal inhibition that they exerted on one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor cortex (M1), premotor cortex (PMC), and supplementary motor cortex (SMA). DTI was used to define interhemispheric differences in the integrity of the corticospinal tracts projecting from the M1. Clinical outcomes tested function (upper extremity Fugl-Meyer [UEFM]) and perceived disability in the use of the paretic hand (Motor Activity Log [MAL] amount score). RESULTS: Interhemispheric balance assessed with TMS relates differently to fMRI and DTI. Patients with high fMRI lateralization to the ipsilesional hemisphere possessed stronger ipsilesional corticomotor output maps (M1: r = .831, P = .006; PMC: r = .797, P = .01) and better balance of mutual transcallosal inhibition (r = .810, P = .015). Conversely, we found that patients with less integrity of the corticospinal tracts in the ipsilesional hemisphere show greater corticospinal output of homologous tracts in the contralesional hemisphere (r = .850, P = .004). However, an imbalance in integrity and output do not relate to transcallosal inhibition. Clinically, although patients with less integrity of corticospinal tracts from the ipsilesional hemisphere showed worse impairments (UEFM) (r = -.768, P = .016), those with low fMRI lateralization to the ipsilesional hemisphere had greater perception of disability (MAL amount score) (M1: r = .883, P = .006; PMC: r = .817, P = .007; SMA: r = .633, P = .062). CONCLUSIONS: In patients with chronic motor deficits of the upper limb, fMRI may serve to mark perceived disability and transcallosal influence between hemispheres. DTI-based integrity of the corticospinal tracts, however, may be useful in categorizing the range of functional impairments of the upper limb. Further, in patients with extensive corticospinal damage, DTI may help infer the role of the contralesional hemisphere in recovery.
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