Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke
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 |
---|---|---|
|
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
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:
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:
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:
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:
|
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:
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:
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:
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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
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
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.- IRB00081268
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
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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
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 |
michael.borich@emory.edu |
- IRB00081268