Imaging Laterality in Chronic Stroke Patients

NCT ID: NCT03584425

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-15
• Study Completion Date: 2019-05-30

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Healthy Controls

Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition

Group Type: EXPERIMENTAL

Rasch modified version of the Fugl-Meyer Motor assessment

Intervention Type: DIAGNOSTIC_TEST

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.

Anatomical image acquisition

Intervention Type: DIAGNOSTIC_TEST

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.

Functional MRI task and acquisition

Intervention Type: DIAGNOSTIC_TEST

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).

Stroke Participants

Subjects will undergo the following diagnostic tasks and assessments: Rasch Modified Version of the Fugl-Meyer Motor Assessment, Anatomical Image Acquisition, and the Functional MRI Task and Acquisition

Group Type: EXPERIMENTAL

Rasch modified version of the Fugl-Meyer Motor assessment

Intervention Type: DIAGNOSTIC_TEST

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.

Anatomical image acquisition

Intervention Type: DIAGNOSTIC_TEST

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.

Functional MRI task and acquisition

Intervention Type: DIAGNOSTIC_TEST

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).

Interventions

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.

Intervention Type: 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.

Intervention Type: 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).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 21-80 years old of any race and ethnicity
• At least 2 cardiovascular risk factors (smoking, high blood pressure, high cholesterol, diabetes, overweight, age (>55 for men, >65 for women), family history of stroke).

• Left middle cerebral artery ischemic stroke with at least 6 month chronicity
• Right upper extremity weakness with a Rasch-modified Fugl-Meyer upper extremity score of 20 to 50
• Ability to voluntarily flex the affected elbow and shoulder from 10-75% of the normal range
• Ability to make a fist and relax the affected hand (note: this motion will be required in the functional MRI task)

Exclusion Criteria

• Primary intracerebral hematoma or subarachnoid hemorrhage
• Bi-hemispheric ischemic strokes
• History of prior right-sided stroke or old infarct demonstrated on the CT or MRI or documented in medical records
• Other concomitant neurological disorders affecting upper extremity motor function
• Documented history of dementia before or after stroke
• Presence of any MRI, TMS, or transcranial direct current stimulation risk factors such as an electrically, magnetically or mechanically activated metal or nonmetal implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system
• Pregnancy as the effect of MRI on the fetus is unknown, females of child bearing age must undergo a pregnancy test to confirm eligibility
• History of seizure disorder or post-stroke seizure
• Preexisting scalp lesion or wound or bone defect or hemicraniectomy
• Left-hand dominance (before the stroke in the stroke patients) as the typical pattern of laterality is not as strong in left-handed healthy individuals
• Current nicotine dependence (Note: nicotine use is not an exclusionary criteria as there is no known association between acute use and BOLD signal changes in non-dependent smokers)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

MUSC Center for Biomedical Research Excellence in Stroke Recovery

UNKNOWN

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Colleen A Hanlon, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

31250

Identifier Type: -

Identifier Source: org_study_id