Late LTP-like Plasticity Effects of tDCS in Chronic Stroke Patients

Study Overview
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Brief Summary
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Rationale: About 80% of stroke patients suffer motor impairments, but current therapies have limited effects on motor recovery. Therefore, investigating new potential therapeutic approaches is crucial. Transcranial Direct Current Stimulation (tDCS) is a form of non-invasive electrical stimulation where a weak current is applied through electrodes over the scalp. This stimulation is known to (1) induce changes in neuronal excitability -which can last up to one day with late LTP-like plasticity protocols- in a polarity and site-specific manner, and (2) facilitate motor learning and stroke recovery. However, it is unknown how the motor cortex excitability changes that follow tDCS relate to the increase in motor learning and recovery potential. The currently upheld hypothesis is that motor learning needs to be synchronized in time with electrical stimulation (paired stimulation), but recent results from our lab suggest that tDCS also increases skill learning after stimulation has ended (unpaired stimulation). If this is true, tDCS has a much larger therapeutic window and is a more valuable clinical tool than currently believed. Therefore, the investigators want to investigate how late LTP-like plasticity tDCS affects the increase in skill learning normally seen with tDCS when applied 24 hours before training. The outcome of this study can provide important guidelines on effective motor therapy during stroke rehabilitation. Objective: Identify the effect of late LTP-like plasticity tDCS in chronic stroke patients on skill learning 24 hours later. Study design: Double-blinded, randomized between-subjects trials. Study population: Chronic stroke patients. Main study parameters/endpoints: The main objective of the study is to determine the effect of late LTP-like plasticity tDCS on skill learning 24 hours later. As a motor learning paradigm, the investigators will use a circuit tracking task which chronic stroke patients perform better if tDCS is applied concurrently. During this task, patients have to trace a cursor over a circuit as fast and accurately as possible by moving a computer mouse. Skill will be quantified by calculating a combined speed/ accuracy score and skill improvement compared to baseline (LI; the learning index) will be compared between the sham, conventional unpaired tDCS, conventional paired tDCS groups and the late LTP-like plasticity tDCS groups.

Conditions
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Stroke, Hemiparesis

Intervention / Treatment
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* Device: Sham
* Device: Conventional Paired tDCS
* Device: Conventional Unpaired tDCS
* Device: Late LTP-like Plasticity tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic (> 6 months) stroke patient Aged 18-79 years Motor deficit in the upper limb due to the stroke Exclusion Criteria: Absence of recordable MEPs from the ADM after TMS Absence of voluntary movement (Fugl-Meyer < III) Head injury or the presence of intracranial metal or intracranial lesions History of cranial irradiation History of epilepsy Presence of a pacemaker Taking anticonvulsant or neuroleptic medication Substance abuse Inability to understand instructions History of psychiatric disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham<br>Day 1: sham stimulation Day 2: sham stimulation | Device: Sham<br>* Bihemispheric 1mA Sham protocol: sham - pause - sham<br>|
| Active Comparator: Conventional Paired tDCS<br>Day 1: sham stimulation Day 2: conventional tDCS | Device: Conventional Paired tDCS<br>* Bihemispheric 1mA Sham protocol: sham - pause - sham Conventional Paired tDCS protocol: 20 minutes tDCS - pause - sham<br>|
| Active Comparator: Conventional Unpaired tDCS<br>Day 1: conventional tDCS Day 2: sham stimulation | Device: Conventional Unpaired tDCS<br>* Bihemispheric 1mA Sham protocol: sham - pause - sham Conventional Unpaired tDCS protocol: 20 minutes tDCS - pause - sham<br>|
| Experimental: Late LTP-like Plasticity tDCS<br>Day 1: late LTP-like Plasticity tDCS Day 2: sham stimulation | Device: Late LTP-like Plasticity tDCS<br>* Bihemispheric 1mA Sham protocol: sham - pause - sham Late LTP-like Plasticity tDCS protocol: 10 minutes tDCS - 25 minutes pause - 10 minutes tDCS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor Skill Retention | Motor skill retention will be assessed on the circuit game | Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Grip Force | Maximum Grip Force will be assessed using a Jamar Dynamometer | Day 1 and Day 9 | 
| Purdue Pegboard Test |  | Day 1 and Day 9 |