Non-invasive Assessment of Synaptic Plasticity

Study Overview
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Brief Summary
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The pathophysiological mechanisms underlying Movement Disorders, including Parkinson's disease, have been related to altered synaptic plasticity affecting several structures of the central nervous system. Although several previous neurophysiologic investigations have shown abnormal long-term potentiation and depression-like plasticity in M1, other regions crucially involved in motor planning and execution, including the spinal cord, have been studied less. Parkinson's disease arises from the progressive loss of dendritic spines followed by atrophy of specific cortical (i.e. M1) and subcortical structures (i.e. putamen). These structural changes are responsible for the main clinical features of PD such as bradykinesia and rigidity. The present research project aims to probe non-invasively the main pathophysiologic mechanisms underlying altered synaptic plasticity in M1 and spinal cord and their relationship in a cohort of patients with movement disorders, including Parkinson's disease. More in detail, the investigators will use specific methodologies able to induce plasticity, including the repetitive transcranial magnetic stimulation (TMS), concerning the M1 and the focal muscle vibration, regarding the spinal cord. The neuromodulation protocol will imply 2 separate sessions, randomly scheduled to take into account the effect of the symptomatic pharmacologic treatment. Furthermore, patients will be randomly assigned to sham or real non-invasive stimulation groups. Before and after the stimulation protocol, the investigators will collect specific clinical as well as neurophysiologic measures (i.e., thresholds) according to standardized procedures. In conclusion, the goal of the study is to investigate the abnormal plasticity in the M1 and spinal cord in patients affected by specific movement disorders, through non-invasive techniques.

Official Title
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Non-invasive Assessment of Brain and Spinal Synaptic Plasticity in Patients Affected by Movement Disorders

Conditions
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Movement Disorders, Parkinson Disease

Intervention / Treatment
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* Device: Device: focal muscle vibration and theta burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical diagnosis of Parkinson's disease Exclusion Criteria: psychiatric disorders, including severe congnitive loss and depression

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Subjects<br>Device: focal muscle vibration to induce spinal plasticity theta burst stimulation and paired associative stimulation to induce plasticity in M1 | Device: Device: focal muscle vibration and theta burst stimulation<br>* non invasive techniques of neuromodulation for inducing plasticity in M1 and spinal cord<br>|
| Patients with Parkinson's disease<br>Device: theta burst stimulation and paired associative stimulation to induce plasticity in M1 Device: focal muscle vibration to induce spinal plasticity | Device: Device: focal muscle vibration and theta burst stimulation<br>* non invasive techniques of neuromodulation for inducing plasticity in M1 and spinal cord<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of neurophysiologic measures | Rest motor threshold | baseline | 
| Analysis of neurophysiologic measures | Active motor threshold | baseline | 
| Analysis of neurophysiologic measures | Amplitude of motor evoked potentials | through study completion, an average of 1 year | 
| Analysis of neurophysiologic measures | H reflex | through study completion, an average of 1 year | 
| Analysis of neurophysiologic measures | input-output curve | through study completion, an average of 1 year |