Premotor Cortex: A New Target for Stroke Motor Rehabilitation

Not Applicable

Suspended

• Conditions: Stroke
• Interventions: Other: Motor Training; Device: rTMS over Premotor Cortex (Contralateral Hemisphere); Device: rTMS over Premotor Cortex (Ipsilateral Hemisphere); Device: rTMS (Control 1); Device: rTMS (Control 2); Device: rTMS (Control 3)

• Registration Number: NCT02565199
• Lead Sponsor: Emory University

Brief Summary

The goal of the study is to determine the effect of repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex on training-related improvements in motor performance and associated neural plasticity.

Detailed Description

Motor training is an important part of recovery after stroke. During motor training, stroke patients practice performing a movement and become better at performing the trained movement over time. Repetitive transcranial magnetic stimulation (rTMS), which uses magnetism to excite neurons near the surface of the brain, may further improve performance. Healthy adults made larger training-related improvements in their motor performance when they received rTMS over the primary motor cortex during motor training. There is evidence that the premotor cortex may be a more effective target than the primary motor cortex for rTMS for some stroke survivors. In the current study, the investigator will determine the effect of rTMS over the premotor cortex on training-related improvements in motor performance in healthy adults.

Study Timeline

• Study Start: 2015-09
• Study First Submitted: 2015-09-29
• Study First Submitted QC: 2015-09-29
• Study First Posted: 2015-10-01
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-14
• Last Update Posted: 2023-08-16
• Primary Completion: 2024-02
• Study Completion: 2024-02

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Motor training only (pilot participants):

• Have the ability to give informed, written consent
• Be aged 18-80 years old
• Be right-handed using the Edinburgh handedness inventory
• Have intact cognitive abilities (score higher than 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS))
• No current depression (score less than 7 on the Hamilton Depression Rating Scale (HDRS))
• No neurological disease
• No contradictions to Transcranial Magnetic Stimulation (TMS)
• TMS over the extensor carpi ulnaris (ECU) hotspot must evoke a motor evoked potential (MEP) in the ECU muscle
• MEP amplitude must increase by at least 20% as the TMS intensity increases
• The subjects must be comfortable when receiving TMS of all strengths.

Remaining study participants:

• Have the ability to give informed, written consent
• Be aged 55-80 years old
• Be right-handed using the Edinburgh handedness inventory
• Have intact cognitive abilities (score higher than 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS))
• No current depression (score less than a 7 on the Hamilton Depression Rating Scale (HDRS))
• No neurological disease
• No contradictions to Transcranial Magnetic Stimulation (TMS)
• TMS over the extensor carpi ulnaris (ECU) hotspot must be able to evoke a motor evoked potential (MEP) in the ECU muscle
• MEP amplitude must increase by at least 20% as the TMS intensity increases
• The subjects must be comfortable when receiving TMS of all strengths.

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Exclusion Criteria

• Impaired cognitive abilities (score lesser than 75th percentile on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS))
• Current depression (score more than 7 on the Hamilton Depression Rating Scale (HDRS))
• Neurological disease
• Has a contradiction to TMS
• MEP cannot be evoked with TMS in the ECU muscle
• Inability to tolerate one or more TMS strengths

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single motor training only	Motor Training	For a pilot experiment, healthy, right-handed subjects will complete one testing session. During the testing session, subjects will complete motor training. The results of this experiment will determine the motor training protocol used in the main experiment.
Repetitive TMS during motor training	Motor Training	Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols.
Repetitive TMS during motor training	rTMS (Control 1)	Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols.
Repetitive TMS during motor training	rTMS (Control 3)	Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols.
Repetitive TMS during motor training	rTMS over Premotor Cortex (Contralateral Hemisphere)	Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols.
Repetitive TMS during motor training	rTMS over Premotor Cortex (Ipsilateral Hemisphere)	Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols.
Repetitive TMS during motor training	rTMS (Control 2)	Healthy, right-handed subjects will complete five testing sessions. During each testing session, subjects will complete motor training while receiving one of five repetitive transcranial magnetic stimulation (rTMS) protocols. Subjects will receive a different rTMS protocol at each testing session. By the end of the study, each subject will have received all rTMS protocols.

Primary Outcome Measures

Name	Time	Method
Change in stimulus response curve (SRC)	Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training)	The stimulus response curve (SRC) is a set of motor evoked potentials (MEPs) collected in response to transcranial magnetic stimulation (TMS) pulses of increasing intensities. The SRC can characterize input-output parameters of the corticospinal tract and organization of the primary motor cortex. A change in the SRC parameters after training will reflect a change in the organization of the primary motor cortex associated with motor learning. We will compare the effect of the rTMS protocols on the change in the SRC parameters associated with motor learning (baseline to post 1 min, baseline to post 30 mins, baseline to post 60 mins).
Change in short interval intracortical inhibition (SICI)	Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training)	Short interval intracortical inhibition (SICI) is an inhibitory phenomenon in the motor cortex. To test for SICI, a sub-threshold conditioning stimulus (CS) will precede a supra-threshold test stimulus (TS) by 2 milliseconds (ms). The amplitude of a conditioned TS-evoked MEP will be expressed as a percent of the amplitude of an unconditioned TS-evoked MEP. A decrease in the percent MEP after training would indicate a increase in SICI. An increase in the percent MEP after training would indicate a decrease in SICI. We will compare the effect of the rTMS protocols on the change in SICI associated with motor learning (baseline to post 1 min, baseline to post 30 mins, baseline to post 60 mins).
Change in wrist acceleration	Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training)	The subjects will be asked to perform 7 isometric wrist extensions before and after motor training. Wrist acceleration will be measured by a gyroscope taped to the dorsum of the subject's hand undergoing motor training. An increase in the maximum acceleration that persists at least an hour after training is indicative of motor learning. We will compare the effect of the rTMS protocols on the change in the wrist acceleration associated with motor learning (baseline to post 1 min, baseline to post 30 mins, baseline to post 60 mins).

Secondary Outcome Measures

Name	Time	Method
Change in wrist force	Baseline, post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training)	The subjects will be asked to perform 7 isometric wrist extensions before and after motor training. A force transducer transducer will record the maximum force produced during the wrist extensions.
Change in reaction time	Baseline and post-motor training (1 minute, 30 minutes and 60 minutes after completion of motor training)	Subjects will be asked to perform 7 auditory-cued ballistic wrist extensions before and after motor training. Electomyographic (EMG) activity recorded during the ballistic wrist extensions will be used to measure reaction time. Reaction time is the length of time between the auditory cue and the onset of the movement-related EMG burst of the extensor carpi ulnaris (ECU) muscle.
Change in task accuracy	Baseline and post-motor training (1 minute after completion of motor training)	Task accuracy will be determined by the number of successful trials over the number of total trials. A trial will be considered successful when the subject moves a cursor from the home position into a target box by modulating the acceleration of their wrist. An increase in task accuracy after training will indicate motor learning.

Trial Locations

Locations (1)

Emory University; 🇺🇸 Atlanta, Georgia, United States