Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke

Sponsor
Emory University (Other)
Overall Status
Terminated
CT.gov ID
NCT02465034
Collaborator
(none)
45
2
2
50.8
22.5
0.4

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Transcranial Magnetic Stimulation
  • Device: Traditional Paired Associative Stimulation
  • Device: Median Nerve Stimulation
  • Device: Corticocortical Paired Associative Stimulation
  • Device: Sham Paired Associative Stimulation
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke
Actual Study Start Date :
May 1, 2015
Actual Primary Completion Date :
Jul 24, 2019
Actual Study Completion Date :
Jul 24, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Subcortical stroke

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.

Device: Transcranial Magnetic Stimulation
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.
Other Names:
  • Magstim BiStim^2
  • Device: Traditional Paired Associative Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Device: Median Nerve Stimulation
    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.

    Device: Corticocortical Paired Associative Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Device: Sham Paired Associative Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Active Comparator: Healthy Control

    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.

    Device: Transcranial Magnetic Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Device: Traditional Paired Associative Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Device: Median Nerve Stimulation
    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.

    Device: Corticocortical Paired Associative Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Device: Sham Paired Associative Stimulation
    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.
    Other Names:
  • Magstim BiStim^2
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Long-term Potentiation-like Plasticity [Baseline, 1 Minute Post-Paired Associative Stimulation]

      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.

    2. Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS [Baseline, 5 Minutes Post-Paired Associative Stimulation]

      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.

    3. Abbreviated Wolf Motor Function Test Time [Baseline, 10 Minutes Post-Paired Associative Stimulation]

      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

    1. Wolf Motor Function Test [Baseline]

      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.

    2. Abbreviated Wolf Motor Function Test Time [30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation]

      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.

    3. Long-term Potentiation-like Plasticity [30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation]

      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.

    4. Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS [30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation]

      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.

    5. Serial Reaction Time Task (SRTT) Performance [Baseline, 10 minutes post-PAS, 30 minutes post-PAS, and 24 hours post-PAS]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Emory University Atlanta Georgia United States 30322
    2 Wesley Woods Center Atlanta Georgia United States 30322

    Sponsors and Collaborators

    • Emory University

    Investigators

    • Principal Investigator: Michael Borich, DPT, PhD, Emory University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Michael R Borich, Associate Professor, Emory University
    ClinicalTrials.gov Identifier:
    NCT02465034
    Other Study ID Numbers:
    • IRB00081268
    First Posted:
    Jun 8, 2015
    Last Update Posted:
    Nov 26, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Michael R Borich, Associate Professor, Emory University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participant enrollment began in May 2015 and all study follow up was completed by July 24, 2019. Study activities took place at the Emory Wesley Woods Health Center in Atlanta, Georgia.
    Pre-assignment Detail Forty-five individuals gave consent to participate in the study and were enrolled into the appropriate study arm based on health status. Four screen failed or withdrew resulting in 41 who participated in the study. Participants with subcortical stroke could take part in both the PAS and CC-PAS studies.
    Arm/Group Title Participants With Subcortical Stroke Healthy Controls
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function undergoing 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 was used where participants received traditional PAS and sham PAS or a cortico-cortical paired associative stimulation (CC-PAS) and sham CC-PAS. Participants also underwent median nerve stimulation. Healthy individuals underwent 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 was used where participants received traditional PAS and sham PAS.
    Period Title: Overall Study
    STARTED 19 26
    Started PAS 12 21
    Completed PAS 9 20
    Started CC-PAS 16 0
    Completed CC-PAS 16 0
    COMPLETED 16 20
    NOT COMPLETED 3 6

    Baseline Characteristics

    Arm/Group Title Participants With Subcortical Stroke Healthy Controls Total
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function undergoing 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 was used where participants received traditional PAS and sham PAS or a cortico-cortical paired associative stimulation (CC-PAS) and sham CC-PAS. Participants also underwent median nerve stimulation. Healthy individuals underwent 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 was used where participants received traditional PAS and sham PAS. Total of all reporting groups
    Overall Participants 19 26 45
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.9
    (12.1)
    26.3
    (6.1)
    39.9
    (18.0)
    Sex: Female, Male (Count of Participants)
    Female
    9
    47.4%
    13
    50%
    22
    48.9%
    Male
    10
    52.6%
    13
    50%
    23
    51.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    3.8%
    1
    2.2%
    Not Hispanic or Latino
    19
    100%
    25
    96.2%
    44
    97.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    4
    15.4%
    4
    8.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    6
    31.6%
    6
    23.1%
    12
    26.7%
    White
    13
    68.4%
    16
    61.5%
    29
    64.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    19
    100%
    26
    100%
    45
    100%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    This analysis includes participants with complete and usable data. Errors with data acquisition occurred with three participants in the stroke PAS assessment, two participants in the stroke CC-PAS assessment, and three healthy controls. Two additional control participants were not included in the analysis due to data quality issues.
    Arm/Group Title Subcortical Stroke PAS Subcortical Stroke PAS Sham Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham Healthy Control Group Healthy Control Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving paired associative stimulation (PAS). 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 is applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham paired associative stimulation (PAS). Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham cortico-cortical paired associative stimulation (CC-PAS). Healthy participants received 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 was also used. Healthy participants receiving sham paired associative stimulation (PAS).
    Measure Participants 6 6 14 14 15 15
    Baseline
    813.86
    (619.81)
    819.47
    (387.37)
    665.14
    (645.05)
    427.80
    (360.45)
    1408.08
    (871.52)
    1025.60
    (451.76)
    1 minute post-PAS
    1455.77
    (1383.06)
    883.74
    (424.24)
    644.46
    (627.70)
    525.34
    (502.67)
    1777.57
    (1192.83)
    1121.38
    (641.96)
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Only participants receiving CC-PAS were studied for this outcome. Errors with data acquisition occurred with two participants. Data were not collected for one participant due to EEG equipment malfunction, and not collected for one participant due to time constraints.
    Arm/Group Title Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham cortico-cortical paired associative stimulation (CC-PAS).
    Measure Participants 12 12
    Baseline
    0.20
    (0.08)
    0.20
    (0.07)
    5 minutes post-PAS
    0.19
    (0.08)
    0.19
    (0.07)
    3. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Only participants receiving CC-PAS were studied for this outcome. Errors with data acquisition occurred with two participants.
    Arm/Group Title Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham cortico-cortical paired associative stimulation (CC-PAS).
    Measure Participants 14 14
    Hand to Table Baseline
    1.34
    (1.00)
    1.20
    (0.94)
    Hand to Table 10 Minutes Post-PAS
    1.22
    (1.04)
    0.98
    (0.76)
    Stack Checkers Baseline
    3.72
    (3.91)
    3.26
    (2.56)
    Stack Checkers 10 Minutes Post-PAS
    3.03
    (2.29)
    3.20
    (2.26)
    Lift Can Baseline
    7.76
    (4.60)
    6.17
    (2.52)
    Lift Can 10 Minutes Post-PAS
    7.40
    (4.47)
    7.19
    (2.93)
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    This analysis includes participants with subcortical stroke, during the active PAS and CC-PAS assessments. Errors with data acquisition occurred with three participants in the stroke PAS assessment and two participants in the stroke CC-PAS assessment. This test was not performed for three participants receiving CC-PAS due to time constraints.
    Arm/Group Title Subcortical Stroke PAS Subcortical Stroke CC-PAS
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving paired associative stimulation (PAS). 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 is applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation.
    Measure Participants 6 11
    Mean (Standard Deviation) [seconds]
    5.79
    (10.74)
    23.30
    (47.81)
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Only participants receiving CC-PAS were studied for this outcome. Errors with data acquisition occurred with two participants.
    Arm/Group Title Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS).
    Measure Participants 14 14
    Hand to Table 30 minutes post-PAS
    1.09
    (0.89)
    1.06
    (0.80)
    Hand to Table 24 hours post-PAS
    1.18
    (0.79)
    1.20
    (1.10)
    Stack Checkers 30 minutes post-PAS
    3.15
    (2.49)
    2.84
    (1.41)
    Stack Checkers 24 hours post-PAS
    3.45
    (4.78)
    2.81
    (2.39)
    Lift Can 30 minutes post-PAS
    7.23
    (3.83)
    7.79
    (5.33)
    Lift Can 24 hours post-PAS
    7.23
    (3.46)
    6.28
    (2.90)
    6. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    This analysis includes participants with complete and usable data. Errors with data acquisition occurred with three participants in the stroke PAS assessment, two participants in the stroke CC-PAS assessment, and three healthy controls. Two additional control participants were not included in the analysis due to data quality issues. Data from one participant with subcortical stroke receiving CC-PAS was not able to be analyzed due to excessive noise in the signal.
    Arm/Group Title Subcortical Stroke PAS Subcortical Stroke PAS Sham Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham Healthy Control Group Healthy Control Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving paired associative stimulation (PAS). 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 is applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham paired associative stimulation (PAS). Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham cortico-cortical paired associative stimulation (CC-PAS). Healthy participants received 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 was also used. Healthy participants receiving sham paired associative stimulation (PAS).
    Measure Participants 6 6 13 14 15 15
    30 minutes post-PAS
    1162.76
    (585.18)
    847.61
    (421.28)
    532.66
    (510.49)
    503.87
    (472.50)
    1757.44
    (960.64)
    1310.29
    (684.84)
    24 hours post-PAS
    1176.71
    (737.16)
    749.86
    (352.13)
    424.17
    (410.79)
    445.29
    (438.84)
    1542.62
    (1219.24)
    1387.98
    (758.53)
    7. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Only participants receiving CC-PAS were studied for this outcome. Errors with data acquisition occurred with two participants. Data were not collected for one participant due to EEG equipment malfunction and not collected for another participant due to time constraints.
    Arm/Group Title Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS).
    Measure Participants 12 12
    30 minutes post-PAS
    0.18
    (0.13)
    0.18
    (0.07)
    24 hours post-PAS
    0.18
    (0.07)
    0.17
    (0.06)
    8. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Errors with data acquisition occurred with three participants in the stroke PAS assessment, two participants in the stroke CC-PAS assessment, and three healthy controls. Two additional control participants were not included due to data quality issues. One participant with subcortical stroke receiving PAS and two receiving CC-PAS were unable to perform the task due to severe upper extremity motor impairment.
    Arm/Group Title Subcortical Stroke PAS Subcortical Stroke PAS Sham Subcortical Stroke CC-PAS Subcortical Stroke CC-PAS Sham Healthy Control Group Healthy Control Sham
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving paired associative stimulation (PAS). 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 is applied 25ms prior to transcranial magnetic stimulation delivery over the ipsilesional (stroke) or non-dominant (control) cortex. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham paired associative stimulation (PAS). Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving cortico-cortical paired associative stimulation (CC-PAS). 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 ranges from 5-15 ms depending on site of stimulation. Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function receiving sham cortico-cortical paired associative stimulation (CC-PAS). Healthy participants received 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 was also used. Healthy participants receiving sham paired associative stimulation (PAS).
    Measure Participants 5 5 12 12 15 15
    Baseline
    805.00
    (188.63)
    1030.26
    (398.40)
    19.21
    (54.01)
    13.02
    (67.51)
    45.13
    (43.68)
    52.30
    (48.71)
    10 minutes post-PAS
    806.00
    (155.60)
    838.12
    (172.58)
    -1.69
    (142.72)
    28.38
    (114.26)
    52.73
    (53.43)
    57.50
    (59.76)
    30 minutes post-PAS
    812.80
    (192.42)
    788.40
    (197.86)
    9.35
    (36.69)
    3.99
    (70.74)
    66.16
    (63.71)
    61.61
    (57.97)
    24 hours post-PAS
    726.00
    (112.81)
    790.25
    (199.97)
    -14.21
    (114.31)
    8.94
    (81.99)
    83.41
    (82.96)
    77.05
    (51.59)

    Adverse Events

    Time Frame Information on adverse events was collected from the time the intervention began through the final follow up assessment (up to 4 weeks).
    Adverse Event Reporting Description
    Arm/Group Title Participants With Subcortical Stroke Healthy Controls
    Arm/Group Description Participants with subcortical stroke in the chronic phase of recovery with mild-moderate impairment of arm function undergoing 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 also underwent median nerve stimulation. Healthy individuals underwent 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 was also used, which was either a traditional or a corticocortical or a sham paired associative stimulation protocol.
    All Cause Mortality
    Participants With Subcortical Stroke Healthy Controls
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/26 (0%)
    Serious Adverse Events
    Participants With Subcortical Stroke Healthy Controls
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/26 (0%)
    Other (Not Including Serious) Adverse Events
    Participants With Subcortical Stroke Healthy Controls
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/26 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Michael Borich
    Organization Emory University
    Phone 404-712-0612
    Email michael.borich@emory.edu
    Responsible Party:
    Michael R Borich, Associate Professor, Emory University
    ClinicalTrials.gov Identifier:
    NCT02465034
    Other Study ID Numbers:
    • IRB00081268
    First Posted:
    Jun 8, 2015
    Last Update Posted:
    Nov 26, 2021
    Last Verified:
    Oct 1, 2021