Noninvasive Brain Stimulation to Evaluate Neural Plasticity After Stroke

Not Applicable

Terminated

• Conditions: Cerebrovascular Stroke
• Interventions: Device: Transcranial Magnetic Stimulation; Device: Traditional Paired Associative Stimulation; Device: Median Nerve Stimulation; Device: Corticocortical Paired Associative Stimulation; Device: Sham Paired Associative Stimulation

• Registration Number: NCT02465034
• Lead Sponsor: Emory University

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.

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-06-03
• Study First Submitted QC: 2015-06-04
• Study First Posted: 2015-06-08
• Primary Completion: 2019-07-24
• Study Completion: 2019-07-24
• Disposition First Submitted: 2021-04-26
• Disposition First Submitted QC: 2021-04-30
• Disposition First Posted: 2021-05-04
• Status Verified: 2021-10
• Results First Submitted: 2021-10-29
• Results First Submitted QC: 2021-10-29
• Last Update Submitted: 2021-10-29
• Results First Posted: 2021-11-26
• Last Update Posted: 2021-11-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (2)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Wesley Woods Center; 🇺🇸 Atlanta, Georgia, United States