Transcranial Magnetic Stimulation in Stroke Motor Rehabilitation Treatment

Targeting Motor Areas for Customized Transcranial Magnetic Stimulation in Motor Rehabilitation Treatment of Chronic Stroke Patients

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.

Occlusion of the middle cerebral artery is the most common cause of stroke. Because the middle cerebral artery supplies blood to the motor cortices, middle cerebral artery stroke often impacts the integrity of the motor cortex and its associated corticospinal projections. Less than half of all individuals post-stroke regain complete motor function. Because motor deficits, especially of the upper extremities, can dampen the quality of life, there is an urgent need to improve current rehabilitation programs to allow more stroke survivors to achieve higher functional gains. Motor training is an important part of recovery after stroke. During motor training, 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. 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 adults who experienced a stroke more than 6 months ago.

Location of single-pulse Transcranial Magnetic Stimulation (sTMS): extensor carpi ulnaris (ECU) hotspot of primary motor cortex (M1).

Repetitive Transcranial magnetic stimulation (rTMS) will be applied over contralateral premotor cortex during motor training. TMS uses magnetism to excite neurons near the surface of the brain. Frequency of rTMS: 0.1 Hz; time of rTMS: 50 milliseconds before the onset of movement-related electromyography (EMG); device: Super Rapid 2 Transcranial Magnetic Stimulator.

Repetitive Transcranial magnetic stimulation (rTMS) will be applied over ipsilateral premotor cortex during motor training. TMS uses magnetism to excite neurons near the surface of the brain. Frequency of rTMS: 0.1 Hz; time of rTMS: 50 milliseconds before the onset of movement-related electromyography (EMG); device: Super Rapid 2 Transcranial Magnetic Stimulator.

Repetitive Transcranial magnetic stimulation (rTMS) will be applied over contralateral primary motor cortex during motor training. TMS uses magnetism to excite neurons near the surface of the brain.Frequency of rTMS: 0.1 Hz; time of rTMS: 50 milliseconds before the onset of movement-related electromyography (EMG); device: Super Rapid 2 Transcranial Magnetic Stimulator.

Sham rTMS will be applied over contralateral premotor cortex. TMS uses magnetism to excite neurons near the surface of the brain. Frequency of rTMS: 0.1 Hz; time of rTMS: 50 milliseconds before the onset of movement-related electromyography (EMG); device: Super Rapid 2 Transcranial Magnetic Stimulator.

Single-pulse TMS will be applied over the extensor carpi ulnaris (ECU) hotspot of primary motor cortex (M1) during motor training.TMS uses magnetism to excite neurons near the surface of the brain. TMS pulses will be applied at different strengths (30%-80% maximum stimulator output) and record subsequent activity of the ECU muscle using electromyography (EMG).

The subjects will be asked to perform 7 isometric wrist extensions before and after motor training. Wrist velocity will be measured by a gyroscope taped to the dorsum of the wrist that was used during motor training. An increase in the maximum velocity that persists at least an hour after training is indicative of motor learning.

To measure organization of a motor region in the primary motor cortex supporting wrist movement, a Stimulus Response Curve (SRC) will be collected before and after motor training. SRC is a set of motor evoked potentials (MEP) that characterizes input-output parameters of the primary motor cortex and associated corticospinal tract. A change in the SRC parameters after training will reflect a change in the organization of the primary motor cortex.

The subjects will be asked to perform 7 isometric wrist extensions before and after motor training. A force transducer will record the maximum force produced during the wrist extensions.

Subjects will be asked to perform 7 auditory-cued ballistic wrist extensions before and after motor training. Electromyographic (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 muscle.

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.

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. The amplitude of a conditioned TS-evoked MEP will be expressed as a percent of the amplitude of an unconditioned TS-evoked MEP (% MEP). A decrease in the % MEP after training would indicate a increase in SICI. An increase in the % MEP after training would indicate a decrease in SICI.

Parametric Estimation by Sequential Testing (PEST) will be used to determine the Resting Motor Threshold (rMT). The mathematical algorithm implemented by PEST will determine the rMT with fewer TMS pulses than the traditional method.

Inclusion Criteria: Have the ability to give informed, written consent Be aged 30-80 years old Have a single ischemic infarction affecting the primary motor system Have intact cognitive abilities No current depression No neurological disease No contradictions to TMS No history of seizures or epilepsy No implanted medical device No metal in neck or head No history of migraine headaches No intake of medication that lowers seizure threshold Exclusion Criteria: none

De-identified individual participant data will be made available for sharing with other researchers. Data will be shared with the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery group. The researchers plan to share the entire data set including clinical, behavioral, anatomical MRI data, with the ENIGMA Stroke Recovery group.

Individual participant data will be available for sharing following publication of primary results from this study, with no end date for sharing.

The format of the shared data will be compatible with the ENIGMA data base. Outside researchers interested in using this data can contact Dr. Buetefisch at cathrin.buetefisch@emory.edu.