Comparison of Measures of Plasticity

Study Overview
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Brief Summary
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Neuroplasticity refers to the ability of the nerve cells to modify their structure or function in response to injury or insult, or other environmental stimuli, with these changes outlasting the period of exposure. Plasticity may be observed as short term or long term changes. In humans, neuroplasticity can be readily assessed in the motor cortex, as excitability changes are demonstrated in the degree to which peripheral muscles are activated, seen through changes in motor-evoked potentials (MEPs). In this study, a number of approaches to assessing neuroplasticity will be evaluated: Paired-associative stimulation (PAS), Theta Burst Stimulation (TBS), which is a form of transcranial magnetic stimulation (TMS) and protocols that combine these two. In addition, participants will complete a computerised 'rotor pursuit task' designed to provide a measure of motor learning. The investigators aim to find the most efficacious (defined by greatest number of responders and effect size as seen in an increase in MEP amplitude) brain stimulation protocol. The investigators will expose the same participants to four excitatory conditioning stimulation paradigms, with each session separated by at least a week. Our hypotheses include: The four conditioning stimulation protocols should increase motor cortical excitability, the investigators therefore expect there to be a significant increase in participant MEPs, with a positive correlation in the increase ofMEP amplitude of the protocols. The investigators do however expect that due to the principles of homeostatic metaplasticity, that the protocols preceded by cTBS will show greater MEP change, due to the lowering of the threshold for LTP plasticity induction. In addition, the investigators expect that an increase in the motor learning manifest by the rotor pursuit task and for there to be a correlation in participants between the increase in MEP amplitude and the improvement in time on target (TOT) shown in the motor learning task (MLT).

Official Title
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Comparison of Measures of Plasticity

Conditions
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Depression, Healthy

Intervention / Treatment
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* Procedure: cTBS-PAS25
* Procedure: cTBS-iTBS
* Procedure: PAS25
* Procedure: iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy controls those suffering depression aged Exclusion Criteria: Significant Neurological illness, including epilepsy Alcohol use above NHRMC guidelines Illicit drug use Electronic implant; such as cochlear implant or pacemaker Musculoskeletal disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PAS25<br>PAS25 refers to the intervention 'paired-associative stimulation' with peripheral ulnar nerve stimulation followed by TMS to the motor cortex 25 ms after. | Procedure: PAS25<br>* PAS25 refers to the intervention 'paired-associative stimulation' with peripheral ulnar nerve stimulation followed by TMS to the motor cortex 25 ms after.<br>* Other names: Digitimer;|
| Experimental: cTBS-PAS<br>40 seconds of continuous Theta-burst stimulation, followed by PAS25 which refers to the intervention 'paired-associative stimulation' with peripheral ulnar nerve stimulation followed by TMS to the motor cortex 25 ms after. | Procedure: cTBS-PAS25<br>* 40 seconds of continuous Theta-burst stimulation, followed by PAS25 which refers to the intervention 'paired-associative stimulation' with peripheral ulnar nerve stimulation followed by TMS to the motor cortex 25 ms after<br>* Other names: Digitimer;|
| Experimental: iTBS<br>190 seconds of intermittent theta-burst stimulation | Procedure: iTBS<br>* 190 seconds of intermittent theta-burst stimulation<br>* Other names: Magstim;|
| Experimental: cTBS-iTBS<br>40 seconds of continuous Theta-burst stimulation, followed by 190 seconds of intermittent Theta-burst stimulation | Procedure: cTBS-iTBS<br>* 40 seconds of continuous Theta-burst stimulation, followed by 190 seconds of intermittent Theta-burst stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| amplitude of motor evoked potentials |  | 60 minutes post brain stimulation protocol intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| motor learning through performance on a 'rotor pursuit task' |  | time frame relates to 5 blocks of 5 trials for each participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paired associative stimulation, theta burst stimulation, transcranial magnetic stimulation, neuroplasticity, healthy controls