title: Assessment of inter-hemispheric imbalance using imaging and noninvasive brain stimulation in patients with chronic stroke.
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.
  
  
  METHODS
  Cross sectional.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Patients with chronic stroke (N = 10; age, 63 ± 9 y) in a population-based sample with unilateral upper-limb paresis.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  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.
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; School of Biomedical Sciences, Kent State University, Kent, OH.
authors.forename: David A
authors.initials: DA
authors.lastname: Cunningham
authors.affiliation: Center for Neurological Restoration, Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Andre
authors.initials: A
authors.lastname: Machado
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Daniel
authors.initials: D
authors.lastname: Janini
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Nicole
authors.initials: N
authors.lastname: Varnerin
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Corin
authors.initials: C
authors.lastname: Bonnett
authors.affiliation: Human Performance and Engineering Laboratory, Kessler Foundation Research Center, West Orange, NJ.
authors.forename: Guang
authors.initials: G
authors.lastname: Yue
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jones
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Mark
authors.initials: M
authors.lastname: Lowe
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Erik
authors.initials: E
authors.lastname: Beall
authors.affiliation: Imaging Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Ken
authors.initials: K
authors.lastname: Sakaie
authors.affiliation: 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.
authors.forename: Ela B
authors.initials: EB
authors.lastname: Plow
mesh_terms: D000368:Aged; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D004185:Disability Evaluation; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D010291:Paresis / Q000175:diagnosis / Q000503:physiopathology*; D011712:Pyramidal Tracts / Q000503:physiopathology; D020521:Stroke / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D034941:Upper Extremity
keywords: Diffusion tensor imaging; MRI, functional; Motor cortex; Rehabilitation; Stroke; Transcranial magnetic stimulation