Operant Conditioning for Neuromodulation

NCT03461159 | Unknown

• 1 other identifier: 201712733
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke; Healthy

Keywords

operant conditioning; H-reflex; motor evoked potential; transcranial magnetic stimulation; motor control

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (6)

• Maximum H-reflex amplitude of an antagonist muscle (wrist extensor)

  baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later

• Motor evoked potential amplitude of an antagonist muscle (wrist extensor)

  baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later

• Wrist motor control total error score

  baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later

• Maximum voluntary isometric contraction

  baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later

• Action Research Arm Test

  baseline, before and after up to 8 weeks of operant conditioning and follow up 3 months later

Study Arms (4)

H-reflex conditioning - Healthy

EXPERIMENTAL

Operant conditioning of H-reflexes in healthy volunteers

Other: Operant conditioning of H-reflexes

H-reflex conditioning - Stroke

EXPERIMENTAL

Operant conditioning of H-reflexes in people post-stroke

Other: Operant conditioning of H-reflexes

MEP conditioning - Healthy

EXPERIMENTAL

Operant conditioning of motor evoked potentials in healthy volunteers

Other: Operant conditioning of motor evoked potentials

MEP conditioning - Stroke

EXPERIMENTAL

Operant conditioning of motor evoked potentials in people post-stroke

Other: Operant conditioning of motor evoked potentials

Interventions

Operant conditioning of H-reflexes OTHER

Spinal reflex responses will be elicited in a wrist flexor muscle using a peripheral nerve stimulator. During training trials, the size of the participant's response will be shown on a screen and the participant will be asked to decrease the size of the H-reflex response over successive trials. Responses that are below a threshold will be rewarded and those above will not.

H-reflex conditioning - Healthy; H-reflex conditioning - Stroke

Operant conditioning of motor evoked potentials OTHER

Motor evoked potentials will be elicited in a wrist flexor muscle using transcranial magnetic stimulation. During training trials, the size of the participant's response will be shown on a screen and the participant will be asked to increase the size of the MEP response over successive trials. Responses that are above a threshold will be rewarded and those below will not.

MEP conditioning - Healthy; MEP conditioning - Stroke

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide informed consent
• Normal function of both upper extremities
• Generally in good health

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Stacey Dejong: lead
• Roy J. Carver Charitable Trust: collaborator
• National Center of Neuromodulation for Rehabilitation: collaborator

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Related Publications (6)

• 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.

  PMID: 16837659 BACKGROUND

• 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.

  PMID: 25143542 BACKGROUND

• 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.

  PMID: 25744889 BACKGROUND

• 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.

  PMID: 24944216 BACKGROUND

• 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.

  PMID: 19420246 BACKGROUND

• 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.

  PMID: 23392666 BACKGROUND

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Stacey L DeJong, PhD, PT

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacey L DeJong, PhD, PT

CONTACT

319-335-6842; stacey-dejong@uiowa.edu

Kim A Streeby

CONTACT

319-384-4735; kimberly-streeby@uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 4, 2018
• First Posted: March 9, 2018
• Study Start: June 8, 2018
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)