Reliability of Paired Associative Stimulation-induced Neuroplasticity After Stroke (PASS)

Paired associative stimulation (PAS) is a non-invasive stimulation method which is known to modulate corticospinal excitability through mechanisms related to long-term potentiation and long-term depression. The purpose of this study is to determine the reliability of individual subject's response (i.e., change in corticospinal excitability) to PAS in patients with chronic stroke (>6 months) with upper limb motor deficits.

Study Overview

• Status: Terminated
• Conditions: Stroke
• Intervention / Treatment: Behavioral: PAS true; Behavioral: PAS sham

Detailed Description

One of the assumptions in stroke rehabilitation is that motor training will lead to motor re-learning and persistent improvements through mechanisms involving neuroplasticity, defined as the ability of the brain to change its structure and function in response to injury, activity, or change in environment. A way to measure a patient's capacity for neuroplasticity may be useful in guiding selection of patients for rehabilitative interventions, or to assess the effect of pharmacological agents on neuroplasticity which may aid in augmenting motor recovery. One method to assess neuroplasticity non-invasively in humans through the use of paired associative stimulation (PAS). PAS is a form of non-invasive stimulation that modulates corticospinal excitability through mechanisms related to long-term potentiation (LTP) and long-term depression (LTD). In PAS, repetitive pairing of peripheral nerve stimulation with a transcranial magnetic stimulation (TMS) pulse over the contralateral motor cortex will increase or decrease corticospinal excitability, depending on the timing between the two stimuli. In healthy subjects and patients with stroke, PAS has successfully been used to facilitate corticospinal excitability as a means to enhance motor performance. In this study, we plan to use PAS as an assay of corticospinal plasticity rather than as a therapeutic intervention in patients with chronic motor deficits (>6 months) due to ischemic stroke.

There is large interindividual variability in individuals' responses to PAS, which may be useful in examining its relationship to motor learning, but the reliability of the measure will need to be assessed prior to using this measure to make inferences about a subject's general capacity to learn motor tasks. The reliability of the response to PAS and its relationship to clinical factors such as stroke severity, has not been well studied in patients with stroke. Results from a preliminary experiment suggest that stroke patients who have a robust response to facilitatory PAS on their unaffected hemisphere have more severe motor deficits than those who do not have a significant response to PAS.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • White Plains, New York, United States, 10605
      • Burke Neurological Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unilateral ischemic stroke with residual arm weakness (Fugl-Meyer Upper Limb < 60) more than 6 months prior to enrollment.
• Ability to give informed consent and understand the tasks involved.
• Age over 18 years.

Exclusion Criteria:

• Hemorrhagic Stroke
• Contraindications to TMS: history of seizure/epilepsy, pacemaker, other neurological disorders, brain surgery, metal implant/fragment in the head, pregnancy
• Taking medications or substances that are known to affect PAS-induced plasticity within the past 2 months: selective serotonin reuptake inhibitors, dopamine, dopamine agonists, haloperidol, lithium, acetylcholinesterase inhibitors, beta-blockers, nimodipine, levetiracetam, ethosuximide, benzodiazepines, baclofen, nicotine
• Peripheral neuropathy or history of nerve injury in the paretic upper limb.
• Social and/or personal circumstances that interfere with ability to return for all study visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PAS true; Participants will receive paired associative stimulation therapy with a modulatory inter-stimulus interval.	Behavioral: PAS true; Participants will receive paired associative stimulation (transcranial magnetic stimulation and peripheral nerve stimulation) with an inter-stimulus interval length known to modulate corticospinal excitability.
Sham Comparator: PAS sham; Participants will receive paired associative stimulation therapy with a non modulatory inter-stimulus interval.	Behavioral: PAS sham; Participants will receive paired associative stimulation (transcranial magnetic stimulation and peripheral nerve stimulation) with an inter-stimulus interval length known to not modulate corticospinal excitability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motor evoked potential amplitude	Assessment of corticospinal excitability	Baseline, up to 30 min Post PAS

Collaborators and Investigators

• Sponsor: Burke Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): September 12, 2022

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: HMRL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No