Cerebrovascular Stroke
Conditions
Keywords
Neural plasticity, Noninvasive brain stimulation, Motor cortex
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.
Interventions
DEVICETranscranial 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.
DEVICETraditional 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.
DEVICEMedian 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.
DEVICECorticocortical 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.
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.
Sponsors
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Subcortical Stroke 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. | 19 |
| Healthy Controls 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. | 26 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Could not be scheduled for study visit | 0 | 5 |
| Overall Study | Screen fail | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Participants With Subcortical Stroke | Healthy Controls | Total |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 12.1 | 26.3 years STANDARD_DEVIATION 6.1 | 39.9 years STANDARD_DEVIATION 18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 25 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 16 Participants | 29 Participants |
| Region of Enrollment United States | 19 Participants | 26 Participants | 45 Participants |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 26 |
| other Total, other adverse events | 0 / 19 | 0 / 26 |
| serious Total, serious adverse events | 0 / 19 | 0 / 26 |
Outcome results
Primary
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.
Time frame: Baseline, 10 Minutes Post-Paired Associative Stimulation
Population: Only participants receiving CC-PAS were studied for this outcome. Errors with data acquisition occurred with two participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Hand to Table Baseline | 1.34 seconds | Standard Deviation 1 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Hand to Table 10 Minutes Post-PAS | 1.22 seconds | Standard Deviation 1.04 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Stack Checkers Baseline | 3.72 seconds | Standard Deviation 3.91 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Stack Checkers 10 Minutes Post-PAS | 3.03 seconds | Standard Deviation 2.29 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Lift Can Baseline | 7.76 seconds | Standard Deviation 4.6 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Lift Can 10 Minutes Post-PAS | 7.40 seconds | Standard Deviation 4.47 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Lift Can Baseline | 6.17 seconds | Standard Deviation 2.52 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Hand to Table Baseline | 1.20 seconds | Standard Deviation 0.94 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Stack Checkers 10 Minutes Post-PAS | 3.20 seconds | Standard Deviation 2.26 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Hand to Table 10 Minutes Post-PAS | 0.98 seconds | Standard Deviation 0.76 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Lift Can 10 Minutes Post-PAS | 7.19 seconds | Standard Deviation 2.93 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Stack Checkers Baseline | 3.26 seconds | Standard Deviation 2.56 |
Primary
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.
Time frame: Baseline, 1 Minute Post-Paired Associative Stimulation
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Change in Long-term Potentiation-like Plasticity | Baseline | 813.86 microvolts (µV) | Standard Deviation 619.81 |
| Subcortical Stroke PAS | Change in Long-term Potentiation-like Plasticity | 1 minute post-PAS | 1455.77 microvolts (µV) | Standard Deviation 1383.06 |
| Subcortical Stroke PAS Sham | Change in Long-term Potentiation-like Plasticity | 1 minute post-PAS | 883.74 microvolts (µV) | Standard Deviation 424.24 |
| Subcortical Stroke PAS Sham | Change in Long-term Potentiation-like Plasticity | Baseline | 819.47 microvolts (µV) | Standard Deviation 387.37 |
| Subcortical Stroke CC-PAS | Change in Long-term Potentiation-like Plasticity | 1 minute post-PAS | 644.46 microvolts (µV) | Standard Deviation 627.7 |
| Subcortical Stroke CC-PAS | Change in Long-term Potentiation-like Plasticity | Baseline | 665.14 microvolts (µV) | Standard Deviation 645.05 |
| Subcortical Stroke CC-PAS Sham | Change in Long-term Potentiation-like Plasticity | Baseline | 427.80 microvolts (µV) | Standard Deviation 360.45 |
| Subcortical Stroke CC-PAS Sham | Change in Long-term Potentiation-like Plasticity | 1 minute post-PAS | 525.34 microvolts (µV) | Standard Deviation 502.67 |
| Healthy Control Group | Change in Long-term Potentiation-like Plasticity | Baseline | 1408.08 microvolts (µV) | Standard Deviation 871.52 |
| Healthy Control Group | Change in Long-term Potentiation-like Plasticity | 1 minute post-PAS | 1777.57 microvolts (µV) | Standard Deviation 1192.83 |
| Healthy Control Sham | Change in Long-term Potentiation-like Plasticity | 1 minute post-PAS | 1121.38 microvolts (µV) | Standard Deviation 641.96 |
| Healthy Control Sham | Change in Long-term Potentiation-like Plasticity | Baseline | 1025.60 microvolts (µV) | Standard Deviation 451.76 |
Primary
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.
Time frame: Baseline, 5 Minutes Post-Paired Associative Stimulation
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS | 5 minutes post-PAS | 0.19 coefficient of coherence | Standard Deviation 0.08 |
| Subcortical Stroke PAS | Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS | Baseline | 0.20 coefficient of coherence | Standard Deviation 0.08 |
| Subcortical Stroke PAS Sham | Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS | Baseline | 0.20 coefficient of coherence | Standard Deviation 0.07 |
| Subcortical Stroke PAS Sham | Electroencephalography Recordings at Baseline and 5 MInutes Post-PAS | 5 minutes post-PAS | 0.19 coefficient of coherence | Standard Deviation 0.07 |
Secondary
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.
Time frame: 30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation
Population: Only participants receiving CC-PAS were studied for this outcome. Errors with data acquisition occurred with two participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Hand to Table 30 minutes post-PAS | 1.09 seconds | Standard Deviation 0.89 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Hand to Table 24 hours post-PAS | 1.18 seconds | Standard Deviation 0.79 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Stack Checkers 30 minutes post-PAS | 3.15 seconds | Standard Deviation 2.49 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Stack Checkers 24 hours post-PAS | 3.45 seconds | Standard Deviation 4.78 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Lift Can 30 minutes post-PAS | 7.23 seconds | Standard Deviation 3.83 |
| Subcortical Stroke PAS | Abbreviated Wolf Motor Function Test Time | Lift Can 24 hours post-PAS | 7.23 seconds | Standard Deviation 3.46 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Lift Can 30 minutes post-PAS | 7.79 seconds | Standard Deviation 5.33 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Hand to Table 30 minutes post-PAS | 1.06 seconds | Standard Deviation 0.8 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Stack Checkers 24 hours post-PAS | 2.81 seconds | Standard Deviation 2.39 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Hand to Table 24 hours post-PAS | 1.20 seconds | Standard Deviation 1.1 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Lift Can 24 hours post-PAS | 6.28 seconds | Standard Deviation 2.9 |
| Subcortical Stroke PAS Sham | Abbreviated Wolf Motor Function Test Time | Stack Checkers 30 minutes post-PAS | 2.84 seconds | Standard Deviation 1.41 |
Secondary
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.
Time frame: 30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS | 30 minutes post-PAS | 0.18 coefficient of coherence | Standard Deviation 0.13 |
| Subcortical Stroke PAS | Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS | 24 hours post-PAS | 0.18 coefficient of coherence | Standard Deviation 0.07 |
| Subcortical Stroke PAS Sham | Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS | 30 minutes post-PAS | 0.18 coefficient of coherence | Standard Deviation 0.07 |
| Subcortical Stroke PAS Sham | Electroencephalography Recordings at 30 Minutes and 24 Hours Post-PAS | 24 hours post-PAS | 0.17 coefficient of coherence | Standard Deviation 0.06 |
Secondary
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.
Time frame: 30 minutes post-Paired Associative Stimulation, 24 hours post-Paired Associative Stimulation
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Long-term Potentiation-like Plasticity | 30 minutes post-PAS | 1162.76 microvolts (µV) | Standard Deviation 585.18 |
| Subcortical Stroke PAS | Long-term Potentiation-like Plasticity | 24 hours post-PAS | 1176.71 microvolts (µV) | Standard Deviation 737.16 |
| Subcortical Stroke PAS Sham | Long-term Potentiation-like Plasticity | 30 minutes post-PAS | 847.61 microvolts (µV) | Standard Deviation 421.28 |
| Subcortical Stroke PAS Sham | Long-term Potentiation-like Plasticity | 24 hours post-PAS | 749.86 microvolts (µV) | Standard Deviation 352.13 |
| Subcortical Stroke CC-PAS | Long-term Potentiation-like Plasticity | 24 hours post-PAS | 424.17 microvolts (µV) | Standard Deviation 410.79 |
| Subcortical Stroke CC-PAS | Long-term Potentiation-like Plasticity | 30 minutes post-PAS | 532.66 microvolts (µV) | Standard Deviation 510.49 |
| Subcortical Stroke CC-PAS Sham | Long-term Potentiation-like Plasticity | 30 minutes post-PAS | 503.87 microvolts (µV) | Standard Deviation 472.5 |
| Subcortical Stroke CC-PAS Sham | Long-term Potentiation-like Plasticity | 24 hours post-PAS | 445.29 microvolts (µV) | Standard Deviation 438.84 |
| Healthy Control Group | Long-term Potentiation-like Plasticity | 24 hours post-PAS | 1542.62 microvolts (µV) | Standard Deviation 1219.24 |
| Healthy Control Group | Long-term Potentiation-like Plasticity | 30 minutes post-PAS | 1757.44 microvolts (µV) | Standard Deviation 960.64 |
| Healthy Control Sham | Long-term Potentiation-like Plasticity | 30 minutes post-PAS | 1310.29 microvolts (µV) | Standard Deviation 684.84 |
| Healthy Control Sham | Long-term Potentiation-like Plasticity | 24 hours post-PAS | 1387.98 microvolts (µV) | Standard Deviation 758.53 |
Secondary
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.
Time frame: Baseline, 10 minutes post-PAS, 30 minutes post-PAS, and 24 hours post-PAS
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcortical Stroke PAS | Serial Reaction Time Task (SRTT) Performance | Baseline | 805.00 milliseconds (ms) | Standard Deviation 188.63 |
| Subcortical Stroke PAS | Serial Reaction Time Task (SRTT) Performance | 10 minutes post-PAS | 806.00 milliseconds (ms) | Standard Deviation 155.6 |
| Subcortical Stroke PAS | Serial Reaction Time Task (SRTT) Performance | 30 minutes post-PAS | 812.80 milliseconds (ms) | Standard Deviation 192.42 |
| Subcortical Stroke PAS | Serial Reaction Time Task (SRTT) Performance | 24 hours post-PAS | 726.00 milliseconds (ms) | Standard Deviation 112.81 |
| Subcortical Stroke PAS Sham | Serial Reaction Time Task (SRTT) Performance | 30 minutes post-PAS | 788.40 milliseconds (ms) | Standard Deviation 197.86 |
| Subcortical Stroke PAS Sham | Serial Reaction Time Task (SRTT) Performance | Baseline | 1030.26 milliseconds (ms) | Standard Deviation 398.4 |
| Subcortical Stroke PAS Sham | Serial Reaction Time Task (SRTT) Performance | 10 minutes post-PAS | 838.12 milliseconds (ms) | Standard Deviation 172.58 |
| Subcortical Stroke PAS Sham | Serial Reaction Time Task (SRTT) Performance | 24 hours post-PAS | 790.25 milliseconds (ms) | Standard Deviation 199.97 |
| Subcortical Stroke CC-PAS | Serial Reaction Time Task (SRTT) Performance | 10 minutes post-PAS | -1.69 milliseconds (ms) | Standard Deviation 142.72 |
| Subcortical Stroke CC-PAS | Serial Reaction Time Task (SRTT) Performance | 30 minutes post-PAS | 9.35 milliseconds (ms) | Standard Deviation 36.69 |
| Subcortical Stroke CC-PAS | Serial Reaction Time Task (SRTT) Performance | Baseline | 19.21 milliseconds (ms) | Standard Deviation 54.01 |
| Subcortical Stroke CC-PAS | Serial Reaction Time Task (SRTT) Performance | 24 hours post-PAS | -14.21 milliseconds (ms) | Standard Deviation 114.31 |
| Subcortical Stroke CC-PAS Sham | Serial Reaction Time Task (SRTT) Performance | Baseline | 13.02 milliseconds (ms) | Standard Deviation 67.51 |
| Subcortical Stroke CC-PAS Sham | Serial Reaction Time Task (SRTT) Performance | 10 minutes post-PAS | 28.38 milliseconds (ms) | Standard Deviation 114.26 |
| Subcortical Stroke CC-PAS Sham | Serial Reaction Time Task (SRTT) Performance | 30 minutes post-PAS | 3.99 milliseconds (ms) | Standard Deviation 70.74 |
| Subcortical Stroke CC-PAS Sham | Serial Reaction Time Task (SRTT) Performance | 24 hours post-PAS | 8.94 milliseconds (ms) | Standard Deviation 81.99 |
| Healthy Control Group | Serial Reaction Time Task (SRTT) Performance | 30 minutes post-PAS | 66.16 milliseconds (ms) | Standard Deviation 63.71 |
| Healthy Control Group | Serial Reaction Time Task (SRTT) Performance | 10 minutes post-PAS | 52.73 milliseconds (ms) | Standard Deviation 53.43 |
| Healthy Control Group | Serial Reaction Time Task (SRTT) Performance | Baseline | 45.13 milliseconds (ms) | Standard Deviation 43.68 |
| Healthy Control Group | Serial Reaction Time Task (SRTT) Performance | 24 hours post-PAS | 83.41 milliseconds (ms) | Standard Deviation 82.96 |
| Healthy Control Sham | Serial Reaction Time Task (SRTT) Performance | 24 hours post-PAS | 77.05 milliseconds (ms) | Standard Deviation 51.59 |
| Healthy Control Sham | Serial Reaction Time Task (SRTT) Performance | 30 minutes post-PAS | 61.61 milliseconds (ms) | Standard Deviation 57.97 |
| Healthy Control Sham | Serial Reaction Time Task (SRTT) Performance | 10 minutes post-PAS | 57.50 milliseconds (ms) | Standard Deviation 59.76 |
| Healthy Control Sham | Serial Reaction Time Task (SRTT) Performance | Baseline | 52.30 milliseconds (ms) | Standard Deviation 48.71 |
Secondary
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.
Time frame: Baseline
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcortical Stroke PAS | Wolf Motor Function Test | 5.79 seconds | Standard Deviation 10.74 |
| Subcortical Stroke PAS Sham | Wolf Motor Function Test | 23.30 seconds | Standard Deviation 47.81 |