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Operant Conditioning for Rehabilitation After Stroke

Primary Purpose

Stroke

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Operant conditioning of motor evoked potentials

About this trial

This is an interventional basic science trial for Stroke focused on measuring operant conditioning, motor evoked potential, transcranial magnetic stimulation, muscle synergy, motor control, motor coordination

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria for aged matched healthy group

Male or female whose age range between 40 and 75
no known neurological injuries

Exclusion criteria for aged matched healthy group

have an orthopedic disorder involving upper limbs;
have a history of any neurologic disease;
have any history of epilepsy of the potential participants and/or their family members;
had an adverse reaction to TMS;
are unable to consent;
are pregnant.

Inclusion criteria for stroke group

male or female hemiparetic chronic stroke survivors;
age ranging between 40-75 year;
with single unilateral ischemic or hemorrhagic middle cerebral artery stroke;
neurologically stable for >6 months;
have an expectation that current medication will be maintained without changes for at least 3 months. Stable use of anti-spasticity medication (e.g., baclofen, diazepam, tizanidine) is accepted;
with moderate-to-severe impairments (FMA<45/66);
with weak wrist extension (i.e., <4 by manual muscle strength test);
eligible to receive transcranial magnetic stimulation (TMS), and extensor carpi radialis (ECR) motor evoked potential (MEP) must be present in the more affected arm;
without severe spasticity (Modified Ashworth (MA) <4);
have not received botulinum toxin on the impaired arm within 3 months.

Exclusion criteria for stroke group

have an orthopedic disorder involving upper limbs;
have no measurable MEP elicited in the ECR;
unable to produce any voluntary ECR EMG activity;
cognitive impairment sufficient to interfere with informed consent or successful completion of the protocol (Montreal Cognitive Assessment (MoCA) score < 26);
a history of another neurologic disease;
a history of vertigo;
a history of vestibular or cochlear dysfunction;
have a history of convulsion or a seizure;
anesthesia of joint position sense in upper limbs;
are pregnant or have a chance that they might be (self-reported);
have metal in the brain/skull (except titanium; e.g. splinters, fragments, clips, etc.);
have cochlear implants;
have an implanted neurostimulator (DBS, epidural/subdural, VNS);
have a cardiac pacemaker or intracardiac lines or metal in the body;
have a medication infusion device;
are taking any medications to treat mental illness;
have spinal or ventricular derivations;
had an adverse reaction to TMS.

Sites / Locations

University of HoustonRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ECR MEP conditioning - Stroke

Arm Description

MEP operant conditioning of ECR in stroke survivors

Outcomes

Primary Outcome Measures

Change in intermuscular coordination patterns (ICoPs)

EMGs will be recorded from 15 muscles. To assess whether wrist extensor MEP OC induces changes in the composition of intermuscular coordination patterns, non-negative matrix factorization will be applied to EMGs to identify and compare ICoPs.

Change in motor evoked potential (MEP)

To measure the amount of the corticospinal excitability of the target muscle (extensor carpi radialis) and its antagonist (flexor carpi radialis), MEPs will be elicited while the participant provides ~30% maximum voluntary contraction level of each muscle background electromyographic (EMG) signals. For all trials, transcranial magnetic stimulation at ~10% above active motor threshold at the optimum location of the cortex will be used to elicit the MEP.

Change in Fugl-Meyer Assessment (FMA) score

To measure severity of motor impairment after stroke, FMA will be performed in the human upper extremity. FMA is commonly used to assess severity of motor impairment and motor recovery. The maximum FMA upper extremity motor score is 66 (i.e., 0: complete motor impairment; 66: normal motor performance). Each item is scored on a 3-point scale (0 = cannot perform, 1 = performs partially, 2 = performs fully).

Change in Action Research Arm Test (ARAT) score

To measure motor function after stroke, ARAT will be performed in the human upper extremity. 19 Items comprising the ARAT are categorized into four subscales (grasp, grip, pinch, and gross movement) and arranged in order of decreasing difficulty, with the most difficult task examined first, followed by the least difficult task. Task performance is rated on a 4-point scale, ranging from 0 (no movement) to 3 (movement performed normally).

Secondary Outcome Measures

Change in force errors that occur during isometric wrist force tracking tasks

As a mechanistic outcome, force errors that occur during isometric wrist force tracking tasks (ramp up-hold-ramp down) will be recorded to assess wrist motor control function that can change as corticospinal excitability increases through MEP up-conditioning.

Full Information

NCT ID

NCT05020080

First Posted

August 13, 2021

Last Updated

July 29, 2023

Sponsor

University of Houston

Collaborators

National Center of Neuromodulation for Rehabilitation

1. Study Identification

Unique Protocol Identification Number

NCT05020080

Brief Title

Operant Conditioning for Rehabilitation After Stroke

Official Title

Examining the Effects of Operant Conditioning of Wrist Extensor MEP on Arm Intermuscular Coordination After Stroke

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 13, 2022 (Actual)

Primary Completion Date

September 30, 2023 (Anticipated)

Study Completion Date

September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Houston

Collaborators

National Center of Neuromodulation for Rehabilitation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The purposes of this study include: To test if multiple upper extremity muscles represented within a discrete primary motor cortex site reflect existing muscle synergies after stroke. To test if altered muscle synergies and intermuscular coordination are malleable to motor evoked potential conditioning that induces corticospinal plasticity for the targeted muscle, wrist extensor carpi radialis

Detailed Description

Stroke is a leading cause of long-term disabilities in the U.S., which can markedly impact the function of the upper extremity (UE). One of the major UE motor impairments is abnormal intermuscular coordination, which leads to impaired post-stroke function and life participation. Also, relatively little is understood about how stroke affects the corticospinal innervation of multiple UE muscles, visualized as multi-muscle motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the primary motor cortex (M1), and its association with intermuscular coordination and impaired UE motor function in stroke. Some studies have shown that improvement in corticospinal excitability for the affected limb may be able to improve intermuscular coordination and enhance motor function recovery after stroke. Operant conditioning is a method that can be used to produce not only targeted plasticity but also wider beneficial plasticity in multiple spinal/supraspinal pathways. Recent studies have shown that MEP operant up-conditioning can increase the corticospinal excitability for the targeted muscle in people with SCI in the UE and lower extremity (LE) and in the LE of multiple sclerosis. For the aim 1 of the project, MEPs elicited by TMS will be applied at the hot spot for the wrist ECR. EMG signal from 15 UE muscle will be collected simultaneously during isometric force generation tasks. This aim will enroll 10 age-matched (age of 40-75 yo) healthy adult and 10 adult (age of 40-75 yo) stroke survivors. Each participant will have a single measurement session. For the aim 2 of the project, 4 randomized out of 10 stroke survivors will perform operant conditioning method of the wrist ECR; also, assessment of the intermuscular coordination, UE Fugl-Meyer (FM), and Action Research Arm Test (ARAT) will be performed. Participants will have three visits per week for 10 weeks for training session. Finally, to test retention of the intervention effect, they will perform two assessment sessions one and three months after finishing the training.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke

Keywords

operant conditioning, motor evoked potential, transcranial magnetic stimulation, muscle synergy, motor control, motor coordination

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ECR MEP conditioning - Stroke

Arm Type

Experimental

Arm Description

MEP operant conditioning of ECR in stroke survivors

Intervention Type

Other

Intervention Name(s)

Operant conditioning of motor evoked potentials

Intervention Description

MEPs elicited by TMS will be applied at the hot spot for the wrist extensor carpi radialis. During training trials, participants will be asked to increase the size of their MEP response. During assessment trials, a physical therapist or occupational therapist will rate the functional level of arm impairment using FMA and ARAT.

Primary Outcome Measure Information:

Title

Change in intermuscular coordination patterns (ICoPs)

Description

Time Frame

before any training, after the 12th and 24th conditioning sessions, respectively, and 1 and 3 months after the 24th conditioning, respectively

Title

Change in motor evoked potential (MEP)

Description

Time Frame

before any training, after the 12th and 24th conditioning sessions, respectively, and 1 and 3 months after the 24th conditioning, respectively

Title

Change in Fugl-Meyer Assessment (FMA) score

Description

Time Frame

Time Frame: before any training, after the 12th and 24th conditioning sessions, respectively, and 1 and 3 months after the 24th conditioning, respectively

Title

Change in Action Research Arm Test (ARAT) score

Description

Time Frame

before any training, after the 12th and 24th conditioning sessions, respectively, and 1 and 3 months after the 24th conditioning, respectively

Secondary Outcome Measure Information:

Title

Change in force errors that occur during isometric wrist force tracking tasks

Description

Time Frame

before any training, after the 12th and 24th conditioning sessions, respectively, and 1 and 3 months after the 24th conditioning, respectively

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria for aged matched healthy group Male or female whose age range between 40 and 75 no known neurological injuries Exclusion criteria for aged matched healthy group have an orthopedic disorder involving upper limbs; have a history of any neurologic disease; have any history of epilepsy of the potential participants and/or their family members; had an adverse reaction to TMS; are unable to consent; are pregnant. Inclusion criteria for stroke group male or female hemiparetic chronic stroke survivors; age ranging between 40-75 year; with single unilateral ischemic or hemorrhagic middle cerebral artery stroke; neurologically stable for >6 months; have an expectation that current medication will be maintained without changes for at least 3 months. Stable use of anti-spasticity medication (e.g., baclofen, diazepam, tizanidine) is accepted; with moderate-to-severe impairments (FMA<45/66); with weak wrist extension (i.e., <4 by manual muscle strength test); eligible to receive transcranial magnetic stimulation (TMS), and extensor carpi radialis (ECR) motor evoked potential (MEP) must be present in the more affected arm; without severe spasticity (Modified Ashworth (MA) <4); have not received botulinum toxin on the impaired arm within 3 months. Exclusion criteria for stroke group have an orthopedic disorder involving upper limbs; have no measurable MEP elicited in the ECR; unable to produce any voluntary ECR EMG activity; cognitive impairment sufficient to interfere with informed consent or successful completion of the protocol (Montreal Cognitive Assessment (MoCA) score < 26); a history of another neurologic disease; a history of vertigo; a history of vestibular or cochlear dysfunction; have a history of convulsion or a seizure; anesthesia of joint position sense in upper limbs; are pregnant or have a chance that they might be (self-reported); have metal in the brain/skull (except titanium; e.g. splinters, fragments, clips, etc.); have cochlear implants; have an implanted neurostimulator (DBS, epidural/subdural, VNS); have a cardiac pacemaker or intracardiac lines or metal in the body; have a medication infusion device; are taking any medications to treat mental illness; have spinal or ventricular derivations; had an adverse reaction to TMS.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jinsook Roh, PhD

Phone

7137432578

jroh@Central.UH.EDU

First Name & Middle Initial & Last Name or Official Title & Degree

Manuel A Portilla-Jiménez, MS, BME

Phone

3467194921

maporti4@cougarnet.uh.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jinsook Roh, Ph.D.

Organizational Affiliation

University of Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77204

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jinsook Roh, PhD

Phone

713-743-2578

jroh@central.uh.edu

First Name & Middle Initial & Last Name & Degree

Manuel A Portilla-Jiménez, MS, BME

Phone

3467194921

maporti4@cougarnet.uh.edu

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25856485

Citation

Ting LH, Chiel HJ, Trumbower RD, Allen JL, McKay JL, Hackney ME, Kesar TM. Neuromechanical principles underlying movement modularity and their implications for rehabilitation. Neuron. 2015 Apr 8;86(1):38-54. doi: 10.1016/j.neuron.2015.02.042.

Results Reference

background

PubMed Identifier

25762917

Citation

McMorland AJ, Runnalls KD, Byblow WD. A neuroanatomical framework for upper limb synergies after stroke. Front Hum Neurosci. 2015 Feb 16;9:82. doi: 10.3389/fnhum.2015.00082. eCollection 2015.

Results Reference

background

PubMed Identifier

19828310

Citation

Tresch MC, Jarc A. The case for and against muscle synergies. Curr Opin Neurobiol. 2009 Dec;19(6):601-7. doi: 10.1016/j.conb.2009.09.002. Epub 2009 Oct 12.

Results Reference

background

PubMed Identifier

23155178

Citation

Roh J, Rymer WZ, Perreault EJ, Yoo SB, Beer RF. Alterations in upper limb muscle synergy structure in chronic stroke survivors. J Neurophysiol. 2013 Feb;109(3):768-81. doi: 10.1152/jn.00670.2012. Epub 2012 Nov 14.

Results Reference

background

PubMed Identifier

25717296

Citation

Roh J, Rymer WZ, Beer RF. Evidence for altered upper extremity muscle synergies in chronic stroke survivors with mild and moderate impairment. Front Hum Neurosci. 2015 Feb 11;9:6. doi: 10.3389/fnhum.2015.00006. eCollection 2015.

Results Reference

background

PubMed Identifier

30625010

Citation

Thompson AK, Fiorenza G, Smyth L, Favale B, Brangaccio J, Sniffen J. Operant conditioning of the motor-evoked potential and locomotion in people with and without chronic incomplete spinal cord injury. J Neurophysiol. 2019 Mar 1;121(3):853-866. doi: 10.1152/jn.00557.2018. Epub 2019 Jan 9.

Results Reference

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PubMed Identifier

30207863

Citation

Thompson AK, Cote RH, Sniffen JM, Brangaccio JA. Operant conditioning of the tibialis anterior motor evoked potential in people with and without chronic incomplete spinal cord injury. J Neurophysiol. 2018 Dec 1;120(6):2745-2760. doi: 10.1152/jn.00362.2018. Epub 2018 Sep 12.

Results Reference

background

PubMed Identifier

30123249

Citation

Thompson AK, Favale BM, Velez J, Falivena P. Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies. Neural Plast. 2018 Jul 15;2018:4725393. doi: 10.1155/2018/4725393. eCollection 2018.

Results Reference

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Operant Conditioning for Rehabilitation After Stroke

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