Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
Overview
- Phase
- Not Applicable
- Intervention
- Carbidopa-Levodopa
- Conditions
- Stroke
- Sponsor
- Emory University
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to use (Transcranial Magnetic Stimulation) TMS or drugs to improve learning of movement skills and the adaptation processes in patients after stroke. Once investigators have determined the improving effect of TMS and the drugs on learning of movement skills, the study team may be able to provide information that improves rehabilitative treatment and helps to improve recovery after stroke.
Detailed Description
Previous studies have shown, that when patients learn a new motor movement, it may cause a change in the way the nerves act in the area of the brain that controls movement. This change is called use-dependent plasticity. The ability of that part of the brain, called the motor cortex (M1), to reorganize plays a major role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. In this proposed study, investigators will further examine influences of use-dependent plasticity in the non-injured M1 of healthy subjects and injured M1 of stroke subjects using a combination of non-invasive cortical stimulation, medication, and exercise techniques. In Aim 1, investigators will test the effect of drugs that interact specifically with different neurotransmitter systems on use-dependent plasticity in intact M1 of healthy humans. In Aim 2, investigators will identify the parameters for non-invasive transcranial magnetic stimulation (TMS) of M1 that are most effective to enhance use-dependent plasticity in intact healthy human M1. In Aim 3, investigators will test the drugs and rTMS protocols that were demonstrated to be most effective to enhance use- dependent plasticity in the Specific Aim 1 and 2 and apply them to participants who have experienced a stroke. Results from this study will help to inform future research about the efficacy of plasticity enhancing methods in injured M1 of stroke patients.
Investigators
Cathrin Buetefisch
Dr. Cathrin Buetefisch
Emory University
Eligibility Criteria
Inclusion Criteria
- •Normal neurological examination
- •Ability to meet criteria of inclusion experiment
- •Ability to give informed consent.
Exclusion Criteria
- •History or neurological or psychiatric disease
- •Abnormal MRI of brain
- •Abnormal neuropsychological testing
- •Intake of CNS active drugs
- •History of seizure disorder
- •History of migraine headaches
- •History of anaphylaxis or allergic reactions
- •Contraindication to TMS
- •Inclusion Criteria:
- •Cerebral ischemic infarction more than 6 months prior to entering the study
Arms & Interventions
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
Intervention: Carbidopa-Levodopa
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
Intervention: Methylphenidate
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
Intervention: Amphetamine Sulfate
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
Intervention: Placebo
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
Intervention: Transcranial Magnetic Stimulation (TMS) Training
Aim 2
Healthy adult female and male subjects will receive repetitive TMS (rTMS) at different times or frequencies with respect to the training movement or sham stimulation.
Intervention: Transcranial Magnetic Stimulation (TMS)
Aim 2
Healthy adult female and male subjects will receive repetitive TMS (rTMS) at different times or frequencies with respect to the training movement or sham stimulation.
Intervention: Sham Transcranial Magnetic Stimulation (TMS)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention: Carbidopa-Levodopa
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention: Methylphenidate
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention: Amphetamine Sulfate
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention: Placebo
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention: Sham Transcranial Magnetic Stimulation (TMS)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
Intervention: Transcranial Magnetic Stimulation (TMS) Training
Outcomes
Primary Outcomes
Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Time Frame: Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.
Aim 1: Mean Peak Acceleration of Wrist Extension Movements
Time Frame: Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.
Secondary Outcomes
- Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) With Respect to Pulse(Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes))
- Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) for rTMS Treatment With Respect to Frequency(Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes))
- Aim 2: Mean Peak Acceleration of Wrist Extension Movements With Respect to Pulse(Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes))
- Aim 2: Mean Peak Acceleration for rTMS Treatment With Respect to Frequency(Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes))
- Aim 3: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)(Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes))
- Aim 3: Mean Peak Acceleration of Wrist Extension Movements(Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes))