NCT03584425

Imaging Laterality in Chronic Stroke Patients

Investigating the Neurobiologic Basis for Loss of Cortical Laterality in Chronic Stroke Patients

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: Medical University of South Carolina · Academic / Other
• Sex: All
• Age: 21 Years – 80 Years
• Healthy volunteers: Accepted

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).

Conditions

• Stroke
• Motor Cortex; Lesion

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Rasch modified version of the Fugl-Meyer Motor assessment	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.
DIAGNOSTIC_TEST	Anatomical image acquisition	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.
DIAGNOSTIC_TEST	Functional MRI task and acquisition	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).

Timeline

• Start date: 2014-12-15
• Primary completion: 2019-05-30
• Completion: 2019-05-30
• First posted: 2018-07-12
• Last updated: 2019-07-23

Locations

1 site across 1 country: United States