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Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke

Primary Purpose

Cerebrovascular Stroke

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Traditional Paired Associative Stimulation
Median Nerve Stimulation
Corticocortical Paired Associative Stimulation
Sham Paired Associative Stimulation
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Cerebrovascular Stroke focused on measuring Neural plasticity, Noninvasive brain stimulation, Motor cortex

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Age between 18-85 years
  2. Middle cerebral artery stroke
  3. Individuals with a first time stroke that affects the corona radiata and/or internal capsule

Exclusion Criteria:

  1. Age outside the age range of 18-85 years
  2. Signs of dementia (score < 24 on the Montreal Cognitive Assessment)
  3. Aphasia (score < 13 on the Frenchay Aphasia Screen)
  4. History of head trauma
  5. History of a major psychiatric diagnosis
  6. History of a neurodegenerative disorder
  7. History of substance abuse
  8. Contraindications to Transcranial Magnetic Stimulation

Sites / Locations

  • Emory University
  • Wesley Woods Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Subcortical stroke

Healthy Control

Arm Description

Subjects with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol. The subjects will also undergo median nerve stimulation.

Healthy individuals will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol.

Outcomes

Primary Outcome Measures

Change in Long-term Potentiation-like Plasticity
Long-term potentiation-like plasticity was measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Participants received 180 paired stimuli at 0.25 hertz (Hz) for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.
Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS
Electroencephalography (EEG) data were recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals were collected at 2000 hertz (Hz) during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Up to fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses were applied to motor cortex while the subject was seated quietly with eyes open. This procedure was conducted bilaterally. Data epochs (-1000 to 4000 ms with respect to TMS delivery) were extracted for subsequent imaginary phase coherence analysis. Post-TMS coherence values between electrodes overlying M1 bilaterally (C3 and C4) were calculated within the beta frequency range (15 to 30 Hz). EEG data values are unit-free that can range from 0 to 1. Higher values represent greater coherence which is thought to indicate stronger connectivity.
Abbreviated Wolf Motor Function Test Time
Three items of the Wolf Motor Function Test (WMFT) were used to evaluate functional motor performance. The 3 items were selected based on task difficulty ranging from easiest (hand to table) to most difficult (stack checkers) along with a task of moderate difficulty (lift can). Each task has different control demands and number of actions required to complete successfully. Task performance is timed in seconds, with a maximum time of 120 seconds.

Secondary Outcome Measures

Wolf Motor Function Test
The arm function in subjects in the subcortical stroke group was evaluated by the Wolf Motor Function Test (WMFT). The test consists of timed and functional tasks and has 17 items. It is composed of 3 parts: Time, functional ability and strength and includes 15 function-based tasks and 2 strength based tasks. Items 1-6 involve timed functional tasks, items 7-14 are measures of strength, and the remaining 9 items consist of analyzing movement quality when completing various tasks. The examiner will test the less affected upper extremity followed by the most affected side. Scores are based on time taken to complete each task. The median time to complete all tasks will be be used to evaluate motor function. Larger values indicate greater upper extremity motor dysfunction.
Abbreviated Wolf Motor Function Test Time
Three items of the WMFT were used to evaluate functional motor performance. The 3 items were selected based on task difficulty ranging from easiest (hand to table) to most difficult (stack checkers) along with a task of moderate difficulty (lift can). Each task has different control demands and number of actions required to complete successfully. Task performance will be timed, with a maximum time of 120 seconds.
Long-term Potentiation-like Plasticity
Long-term potentiation-like plasticity was measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Participants receive 180 paired stimuli at 0.25 Hz for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.
Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS
Electroencephalography (EEG) data were recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals were collected at 2000 hertz (Hz) during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Up to fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses were applied to motor cortex while the subject was seated quietly with eyes open. This procedure was conducted bilaterally. Data epochs (-1000 to 4000 ms with respect to TMS delivery) were extracted for subsequent imaginary phase coherence analysis. Post-TMS coherence values between electrodes overlying M1 bilaterally (C3 and C4) were calculated within the beta frequency range (15 to 30 Hz). EEG data values are unit-free that can range from 0 to 1. Higher values represent greater coherence which is thought to indicate stronger connectivity.
Serial Reaction Time Task (SRTT) Performance
The SRTT involves pressing a key that corresponds to a target square positioned on a screen in front of the participant as quickly and accurately as possible. The response time for repeated and random sequences evaluate SRTT performance and skill is measured as the difference in response times between repeated and random sequences. Lower response times indicate better performance and a larger positive difference in response times represents greater sequence-specific skill. Negative values represent better performance on random sequences compared to repeated sequences.

Full Information

First Posted
June 3, 2015
Last Updated
October 29, 2021
Sponsor
Emory University
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1. Study Identification

Unique Protocol Identification Number
NCT02465034
Brief Title
Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke
Official Title
Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Enrollment and study activities were suspended due to COVID-19.
Study Start Date
May 2015 (Actual)
Primary Completion Date
July 24, 2019 (Actual)
Study Completion Date
July 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to examine how different areas in the brain interact with each other and how using brain imaging and brain stimulation approaches can influence these interactions.
Detailed Description
Subcortical strokes affect small vessels deep in the brain, and typically present with motor hemiparesis. The investigator will assess the effects of Transcranial Magnetic Stimulation (TMS) on motor function and examine how different areas in the human brain interact with each other using brain imaging and brain stimulation. The investigator will also evaluate the capacity for noninvasive stimulation to transiently modify brain activity supporting arm movement.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebrovascular Stroke
Keywords
Neural plasticity, Noninvasive brain stimulation, Motor cortex

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subcortical stroke
Arm Type
Active Comparator
Arm Description
Subjects with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol. The subjects will also undergo median nerve stimulation.
Arm Title
Healthy Control
Arm Type
Active Comparator
Arm Description
Healthy individuals will undergo noninvasive targeting of cortical locations by stereotactic neuronavigation using Transcranial Magnetic Stimulation (TMS), median nerve stimulation and arm motor function assessments. A paired associative stimulation (PAS) protocol using noninvasive stimulation will also be used which will be one of the following, a traditional or a corticocortical or a sham paired associative stimulation protocol.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Other Intervention Name(s)
Magstim BiStim^2
Intervention Description
Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator to measure transient cortical excitability. Single pulse transcranial magnetic stimulation applied at low frequencies (not greater than 0.25 hertz (Hz)) will be used. The may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.
Intervention Type
Device
Intervention Name(s)
Traditional Paired Associative Stimulation
Other Intervention Name(s)
Magstim BiStim^2
Intervention Description
Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25 Hz for 12 minutes. Median nerve stimuli at 300% of the perceptual threshold will be applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Transcranial Magnetic Stimulation (TMS) will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This traditional paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.
Intervention Type
Device
Intervention Name(s)
Median Nerve Stimulation
Intervention Description
Stimulation of the median nerve will be performed using a bipolar bar electrode affixed to palmar aspect of the forearm proximal to the crease of the wrist bilaterally. Stimuli will be delivered 23ms prior to the transcranial magnetic stimulation (TMS) pulse with 0.1 milliseconds (ms) rectangular pulses at an intensity to evoke a 1 millivolt (mV) response in the abductor pollicis brevis (APB) muscle. This may may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.
Intervention Type
Device
Intervention Name(s)
Corticocortical Paired Associative Stimulation
Other Intervention Name(s)
Magstim BiStim^2
Intervention Description
Cortico-cortical Paired Associative Stimulation (CC-PAS) is a combination of TMS and electrical stimulation of the median nerve. 180 paired stimuli are delivered at 0.25 Hz for 12 minutes. The interstimulus interval will range from 5-15 ms depending on site of stimulation.TMS will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This CC-PAS may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.
Intervention Type
Device
Intervention Name(s)
Sham Paired Associative Stimulation
Other Intervention Name(s)
Magstim BiStim^2
Intervention Description
The sham PAS is a combination of TMS and electrical stimulation of the median nerve. The coil is rotated and separated from the head with a plastic spacer to ensure indirect contact with the head.180 paired stimuli are delivered at 0.25 Hz for 12 minutes. TMS will be performed using the Magstim BiStim^2 paired pulse stimulator unit and a bipolar bar electrode will be used for median nerve stimulation. This sham paired associative stimulation may be repeated at multiple study visits. All five study visits will be completed within four weeks of the initial visit.
Primary Outcome Measure Information:
Title
Change in Long-term Potentiation-like Plasticity
Description
Long-term potentiation-like plasticity was measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Participants received 180 paired stimuli at 0.25 hertz (Hz) for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.
Time Frame
Baseline, 1 Minute Post-Paired Associative Stimulation
Title
Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS
Description
Electroencephalography (EEG) data were recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals were collected at 2000 hertz (Hz) during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Up to fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses were applied to motor cortex while the subject was seated quietly with eyes open. This procedure was conducted bilaterally. Data epochs (-1000 to 4000 ms with respect to TMS delivery) were extracted for subsequent imaginary phase coherence analysis. Post-TMS coherence values between electrodes overlying M1 bilaterally (C3 and C4) were calculated within the beta frequency range (15 to 30 Hz). EEG data values are unit-free that can range from 0 to 1. Higher values represent greater coherence which is thought to indicate stronger connectivity.
Time Frame
Baseline, 5 Minutes Post-Paired Associative Stimulation
Title
Abbreviated Wolf Motor Function Test Time
Description
Three items of the Wolf Motor Function Test (WMFT) were used to evaluate functional motor performance. The 3 items were selected based on task difficulty ranging from easiest (hand to table) to most difficult (stack checkers) along with a task of moderate difficulty (lift can). Each task has different control demands and number of actions required to complete successfully. Task performance is timed in seconds, with a maximum time of 120 seconds.
Time Frame
Baseline, 10 Minutes Post-Paired Associative Stimulation
Secondary Outcome Measure Information:
Title
Wolf Motor Function Test
Description
The arm function in subjects in the subcortical stroke group was evaluated by the Wolf Motor Function Test (WMFT). The test consists of timed and functional tasks and has 17 items. It is composed of 3 parts: Time, functional ability and strength and includes 15 function-based tasks and 2 strength based tasks. Items 1-6 involve timed functional tasks, items 7-14 are measures of strength, and the remaining 9 items consist of analyzing movement quality when completing various tasks. The examiner will test the less affected upper extremity followed by the most affected side. Scores are based on time taken to complete each task. The median time to complete all tasks will be be used to evaluate motor function. Larger values indicate greater upper extremity motor dysfunction.
Time Frame
Baseline
Title
Abbreviated Wolf Motor Function Test Time
Description
Three items of the WMFT were used to evaluate functional motor performance. The 3 items were selected based on task difficulty ranging from easiest (hand to table) to most difficult (stack checkers) along with a task of moderate difficulty (lift can). Each task has different control demands and number of actions required to complete successfully. Task performance will be timed, with a maximum time of 120 seconds.
Time Frame
30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation
Title
Long-term Potentiation-like Plasticity
Description
Long-term potentiation-like plasticity was measured using paired associative stimulation (PAS). PAS consists of repeated peripheral electric stimulation paired with Transcranial Magnetic Stimulation (TMS) applied to the motor cortex at varying interstimulus intervals. Participants receive 180 paired stimuli at 0.25 Hz for 12 minutes. Impaired long-term potentiation-like plasticity points towards reduced excitatory synaptic connectivity and deficits in sensorimotor integration. Decrease or no change in the amplitudes of motor-evoked potentials (MEPs) indicates impaired long-term potentiation-like plasticity.
Time Frame
30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation
Title
Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS
Description
Electroencephalography (EEG) data were recorded using a 64-channel TMS-compatible electrode cap (Easy Cap). Signals were collected at 2000 hertz (Hz) during pre- and post-transcranial magnetic stimulation epochs (-100ms to 200ms). Up to fifty suprathreshold (120% AMT) transcranial magnetic stimulation pulses were applied to motor cortex while the subject was seated quietly with eyes open. This procedure was conducted bilaterally. Data epochs (-1000 to 4000 ms with respect to TMS delivery) were extracted for subsequent imaginary phase coherence analysis. Post-TMS coherence values between electrodes overlying M1 bilaterally (C3 and C4) were calculated within the beta frequency range (15 to 30 Hz). EEG data values are unit-free that can range from 0 to 1. Higher values represent greater coherence which is thought to indicate stronger connectivity.
Time Frame
30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation
Title
Serial Reaction Time Task (SRTT) Performance
Description
The SRTT involves pressing a key that corresponds to a target square positioned on a screen in front of the participant as quickly and accurately as possible. The response time for repeated and random sequences evaluate SRTT performance and skill is measured as the difference in response times between repeated and random sequences. Lower response times indicate better performance and a larger positive difference in response times represents greater sequence-specific skill. Negative values represent better performance on random sequences compared to repeated sequences.
Time Frame
Baseline, 10 minutes post-PAS, 30 minutes post-PAS, and 24 hours post-PAS

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age between 18-85 years Middle cerebral artery stroke Individuals with a first time stroke that affects the corona radiata and/or internal capsule Exclusion Criteria: Age outside the age range of 18-85 years Signs of dementia (score < 24 on the Montreal Cognitive Assessment) Aphasia (score < 13 on the Frenchay Aphasia Screen) History of head trauma History of a major psychiatric diagnosis History of a neurodegenerative disorder History of substance abuse Contraindications to Transcranial Magnetic Stimulation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Borich, DPT, PhD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Wesley Woods Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29721010
Citation
Borich MR, Wolf SL, Tan AQ, Palmer JA. Targeted Neuromodulation of Abnormal Interhemispheric Connectivity to Promote Neural Plasticity and Recovery of Arm Function after Stroke: A Randomized Crossover Clinical Trial Study Protocol. Neural Plast. 2018 Mar 12;2018:9875326. doi: 10.1155/2018/9875326. eCollection 2018.
Results Reference
derived

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Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke

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