Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal neurological examination
- •Ability to meet criteria of inclusion experiment
- •Ability to give informed consent.
排除标准
- •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
- •Single lesion as defined by MRI of the brain affecting the primary motor output system of the hand at a cortical (M1) level or subcortical level, or unilateral, and supratentorial in absence of history of a previous symptomatic stroke within 3 months of the current stroke
- •Dense paresis of the hand for more than three days after cerebral infarction (MRC of < 4- of wrist- and finger extension/flexion movements)
- •Good functional recovery of hand function as defined by MRC of 4 or 4+ of wrist- and finger extension/flexion movements
- •Ability to perform wrist extension movements
- •Ability to meet criteria of inclusion experiment
- •Ability to give informed consent
- •Ability of TMS to elicit a measurable MEP of > 100 μV and an increase in MEP amplitude with increasing stimulus intensity (up to 100% of MSO) of at least 20% over MEP amplitude at MT
- •Exclusion Criteria:
- •History or neurological or psychiatric disease, including bipolar disorder
- •Intake of CNS active drugs
- •History of seizure disorder
- •History of migraine headaches
- •History of anaphylaxis or allergic reactions
- •Contraindication to TMS
研究组 & 干预措施
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
干预措施: Carbidopa-Levodopa (Drug)
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
干预措施: Methylphenidate (Drug)
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
干预措施: Amphetamine Sulfate (Drug)
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
干预措施: Placebo (Drug)
Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
干预措施: Transcranial Magnetic Stimulation (TMS) Training (Other)
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.
干预措施: Transcranial Magnetic Stimulation (TMS) (Other)
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.
干预措施: Sham Transcranial Magnetic Stimulation (TMS) (Other)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
干预措施: Carbidopa-Levodopa (Drug)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
干预措施: Methylphenidate (Drug)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
干预措施: Amphetamine Sulfate (Drug)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
干预措施: Placebo (Drug)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
干预措施: Sham Transcranial Magnetic Stimulation (TMS) (Other)
Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
干预措施: Transcranial Magnetic Stimulation (TMS) Training (Other)
结局指标
主要结局
Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
时间窗: 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
时间窗: 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.
次要结局
- 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))
研究者
Cathrin Buetefisch
Dr. Cathrin Buetefisch
Emory University