Imaging Laterality in Chronic Stroke Patients
Condition: Stroke; Motor Cortex; Lesion
MeSH terms: Stroke
Study type: Interventional
Phase: Early Phase 1

Summary: 
      In healthy individuals, unimanual movement (with either the left or right hand) is associated
      with activity in a network of predominantly contralateral brain regions, including the
      primary motor cortex (PMC). This laterality is often compromised following a middle cerebral
      artery (MCA) stroke. Neuroimaging studies of these patients have shown that unimanual
      movements with the effected hand are associated with elevated Blood Oxygen-Level Dependent
      (BOLD) signal in both the lesioned and the nonlesioned primary motor cortices. Elevated
      activity in the contralesional PMC is well-established in chronic stroke patients and is
      associated with poor motor rehabilitation outcomes. Yet the neurobiologic basis for this
      aberrant neural activity is equivocal. The overarching goal of this project is to determine
      the neurobiologic basis for elevated activity in the contralesional primary motor cortex.
    

Detailed description: 
      One factor that may contribute to elevated activity in the contralesional PMC is increased
      cortical excitatory tone within the contralesional hemisphere (Aim 1).

      While approximately 80% of the descending corticospinal neurons that control the right hand
      originate in the left PMC, 20% originate in the right PMC. Elevated activity in the right PMC
      of left-sided stroke patients may reflect compensatory activity of these descending fibers.
      Neural activity in the PMC reflects the balance of local excitatory (glutamatergic) and
      inhibitory (GABAergic) processing. It can be measured in two manners: 1)
      electrophysiologically, using single hemisphere paired pulse transcranial magnetic
      stimulation (TMS), and 2) neurochemically, using magnetic resonance spectroscopy (MRS).

      Another factor that may contribute to elevated activity in the contralesional PMC is a loss
      of transcallosal inhibition between the hemispheres (Aim 2). During right hand movement, the
      left PMC of healthy individuals actively inhibits the right PMC via inhibitory projections
      through the corpus callosum. In left MCA stroke patients, elevated activity in the
      contralesional (right) PMC when moving the right hand may reflect a loss of typical
      inhibition from the left PMC. The integrity of inter-hemispheric information transfer can be
      measured in two manners: 1) using bi-hemispheric paired-pulse TMS, and 2) using a multimodal
      brain stimulation/brain imaging approach, interleaved TMS/MRI.

      Through interleaved TMS/MRI, the investigators can selectively stimulate the ipsilesional PMC
      and quantify the amount of TMS-induced activity in the contralesional PMC. These two
      explanations will be tested through a cross-sectional investigation of neural function in
      left MCA stroke patients with mild-moderate right upper extremity impairment and controls
      matched for age and cardiovascular risk factors. To assess the clinical relevance of these
      factors on motor dysfunction, the investigators will perform a detailed kinematic assessment
      of movement efficiency, smoothness and compensation (Aim 3).
    

Intervention name(s): Rasch modified version of the Fugl-Meyer Motor assessment; Anatomical image acquisition; Functional MRI task and acquisition
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): All participants will receive a comprehensive clinical assessment of motor function including the Rasch modified version of the Fugl-Meyer Motor assessment and a kinematic assessment of unimanual and bimanual movements using a 45 sensor 3D active marker based motion capture system. The three primary measures investigated in the kinematics include: 1) movement efficiency, 2) movement smoothness, and 3) motor compensation.; High-resolution structural scans will be obtained using an inversion recovery 3D spoiled gradient echo (3DSPGR) sequence using a matrix size of 256 x 256, field of view of 24 cm, section thickness of 1.5 mm with no gap between sections, and 128 slices, giving an in-plane resolution of 0.94 mm. This sequence will be used for anatomic overlays of the functional data and for spatial normalization to a standard atlas.; Briefly, patients will be given two pressure-sensitive bulbs (one to be held in each hand and fastened lightly to their wrists with Velcro such that they do not drop it during the scan. During two 2½ minute runs they will be prompted to squeeze the bulb in either their affected or unaffected hand in blocks of 15 seconds. These blocks will be interspersed with blocks of rest. The pressure from the bulbs will be digitally recorded and quantified offline in order to: 1) verify that the patient was squeezing the ball, and 2) assess the presence of 'mirror movements' from the opposing hand that may inform the imaging results regarding loss of laterality).
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: The investigators will enroll a total of 30 chronic stroke patients and 30 neurologically healthy controls matched for age and with at least 2 cardiovascular risk factors
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: BOLD Signal; Functional Magnetic Resonance Imaging; MR Spectroscopy; Anatomical Imaging; Kinematics