Healthy Clinical Trial
Official title:
Operant Conditioning of Spinal Reflexes and Motor Evoked Potentials
NCT number | NCT03461159 |
Other study ID # | 201712733 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | June 8, 2018 |
Est. completion date | June 30, 2024 |
Emerging evidence demonstrates that animals and people can exert control over the level of excitability in spinal and corticospinal neural circuits that contribute to movement. This discovery has important implications, as it represents a new strategy to improve motor control in people of all ability levels, including those with neurological conditions. Operant conditioning is a well-studied mechanism of learning, in which the modification of a behavior can be brought about by the consequence of the behavior, and reinforcement causes behaviors to become more frequent. In recent years, operant conditioning has been applied to spinally-mediated reflex responses in mice, rats, monkeys and people. By electrically stimulating a peripheral nerve, recording the muscle response, and rewarding responses that are within a desirable range, it is possible to increase or decrease the neural circuit's excitability. This may alter the level of resting muscle tone and spasticity, as well the muscle's contribution to planned movements and responses to unexpected events. Operant conditioning of spinal reflexes has been applied to a lower limb muscle in healthy people and those with spinal cord injuries. In this project, we will expand the use of operant conditioning to muscles of the upper limb, demonstrating feasibility and efficacy in healthy people and people post-stroke. We will determine whether operant conditioning can be used to decrease excitability of spinal reflexes that activate a wrist flexor muscle. Additionally, in a separate group of healthy people, we will determine whether operant conditioning can be used in a similar way to increase corticospinal excitability. We will stimulate the motor cortex with transcranial magnetic stimulation to elicit motor evoked potentials in the same wrist flexor muscle, and will reward responses that exceed a threshold value. We will examine the effects of these interventions on motor control at the wrist, using an innovative custom-designed cursor-tracking task to quantify movement performance. We will determine whether changes in spinal reflex excitability or corticospinal excitability alter motor control. The overall goal of this research is to develop a new, evidence-based strategy for rehabilitation that will improve recovery of upper limb function in people after stroke.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | June 30, 2024 |
Est. primary completion date | June 30, 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 21 Years to 90 Years |
Eligibility | Inclusion Criteria for Healthy Group: - Able and willing to provide informed consent - Normal function of both upper extremities - Generally in good health Exclusion Criteria for Healthy Group: - Any self-reported disease or disorder that might affect this study, including neurologic, psychiatric, muscular, orthopedic, cardiac, vascular, pulmonary, hematologic, infectious, immune, gastrointestinal, urogenital, integumentary, oncologic, or endocrine conditions - Any self-reported or demonstrated loss of sensation, passive range of motion, or motor function affecting any part of the upper limb on either side Inclusion Criteria for Stroke Group: - Able and willing to provide informed consent - Subcortical ischemic stroke OR incomplete spinal cord injury, diagnosed by a neurologist at least 3 months before enrollment - Upper limb sensorimotor impairment on one or both sides, as indicated by a score of 10 to 56 out of 66 points on the Fugl-Meyer Assessment of the Upper Extremity - Cognitive ability that is normal or only mildly impaired, as indicated by a score of 9 or less on the Short Blessed Test - Normal receptive and expressive language abilities, as indicated by a score of 0 on the Best Language item of the National Institutes of Health Stroke Scale Exclusion Criteria for Stroke Group: - Any self-reported or medically documented disease or disorder that might affect this study, including other neurologic conditions besides stroke or spinal cord injury, psychiatric, muscular, orthopedic, cardiac, vascular, pulmonary, hematologic, infectious, immune, gastrointestinal, urogenital, integumentary, oncologic, or endocrine conditions - Diagnosis of hemorrhagic stroke or hemorrhagic conversion - Diagnosis of an infarct affecting the motor cortex |
Country | Name | City | State |
---|---|---|---|
United States | University of Iowa | Iowa City | Iowa |
Lead Sponsor | Collaborator |
---|---|
Stacey Dejong | National Center of Neuromodulation for Rehabilitation, Roy J. Carver Charitable Trust |
United States,
Carp JS, Tennissen AM, Chen XY, Wolpaw JR. H-reflex operant conditioning in mice. J Neurophysiol. 2006 Oct;96(4):1718-27. doi: 10.1152/jn.00470.2006. Epub 2006 Jul 12. — View Citation
Chen Y, Chen L, Wang Y, Wolpaw JR, Chen XY. Persistent beneficial impact of H-reflex conditioning in spinal cord-injured rats. J Neurophysiol. 2014 Nov 15;112(10):2374-81. doi: 10.1152/jn.00422.2014. Epub 2014 Aug 20. — View Citation
Majid DS, Lewis C, Aron AR. Training voluntary motor suppression with real-time feedback of motor evoked potentials. J Neurophysiol. 2015 May 1;113(9):3446-52. doi: 10.1152/jn.00992.2014. Epub 2015 Mar 4. — View Citation
Makihara Y, Segal RL, Wolpaw JR, Thompson AK. Operant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans. J Neurophysiol. 2014 Sep 15;112(6):1439-46. doi: 10.1152/jn.00225.2014. Epub 2014 Jun 18. — View Citation
Thompson AK, Chen XY, Wolpaw JR. Acquisition of a simple motor skill: task-dependent adaptation plus long-term change in the human soleus H-reflex. J Neurosci. 2009 May 6;29(18):5784-92. doi: 10.1523/JNEUROSCI.4326-08.2009. — View Citation
Thompson AK, Pomerantz FR, Wolpaw JR. Operant conditioning of a spinal reflex can improve locomotion after spinal cord injury in humans. J Neurosci. 2013 Feb 6;33(6):2365-75. doi: 10.1523/JNEUROSCI.3968-12.2013. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum H-reflex amplitude of target muscle (wrist flexor) | After operant conditioning of H-reflexes, the pre-training vs post-training change in the maximum H-reflex, identified using recruitment curves, will be the primary outcome measure. | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Primary | Motor evoked potential amplitude of target muscle (wrist flexor) | After operant conditioning of motor evoked potentials, the pre-training vs post-training change in the MEP amplitude for the target muscle will be the primary outcome measure. Stimulus intensity will be kept constant during pre and post testing (e.g. 110% of the baseline resting motor threshold). | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Secondary | Maximum H-reflex amplitude of an antagonist muscle (wrist extensor) | pre-training vs post-training change in the maximum H-reflex of the antagonist muscle, identified using recruitment curves | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Secondary | Motor evoked potential amplitude of an antagonist muscle (wrist extensor) | Pre-training vs post-training change in the motor evoked potential amplitude for the antagonist muscle. | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Secondary | Wrist motor control total error score | Wrist motor control will be assessed using a novel instrumented device and a computer-based force-tracking task that requires a high level of precise motor control at the wrist. | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Secondary | Maximum voluntary isometric contraction | Maximum wrist flexion force production | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Secondary | Action Research Arm Test | For participants with stroke only, this standardized test will be used to quantify upper limb function. | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later | |
Secondary | Fugl-Meyer Assessment of the Upper Extremity | For participants with stroke only, this standardized test will be used to quantify upper limb impairment. | baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later |
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