Transcranial Brain Stimulation in Vegetative State Patients

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to determine whether transcranial brain stimulations, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), are effective in terms of EEG coherence and clinical changes in patients in vegetative and minimally conscious state.

Official Title
-----------------
Study on the Use of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation to Promote Diagnosis, Prognosis and Innovative Rehabilitation in Patients in Vegetative and Minimally Conscious State.

Conditions
-----------------
Vegetative State, Minimally Conscious State

Intervention / Treatment
-----------------
* Device: Transcranial direct current stimulation (tDCS)
* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
* Device: Transcranial Direct Current Stimulation (SHAM)
* Device: Repetitive Transcranial Magnetic Stimulation (SHAM)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of vegetative state od minimally conscious state defined by the Disability Rating Scale with a score between 17 and 29. Age between 18 and 65 years. Time from the lesion: more than 4 months. Stable clinical condition. written consent fron the legal administrator of the patient. Exclusion Criteria: Presence of epileptiform activity on EEG. Previous history of epilepsy. Extensive hemorrhage or ischemia. Metallic clips or intracranial implants. Pacemaker e Baclofen infusion. Presence of drugs influencing arousal or awareness.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brain stimulation<br>Brain stimulation will consist of 4 types of intervention: real transcranial direct current stimulation (two weeks, five days a week) a week of wash-out Sham transcranial direct current stimulation (two weeks, five days a week) two weeks of wash-out real repetitive transcranial magnetic stimulation (two weeks, four days a week) a week of wash-out Sham repetitive transcranial magnetic stimulation (two weeks, three days a week) Stimulations will be counterbalanced between patients. | Device: Transcranial direct current stimulation (tDCS)<br>* 2 mA of intensity, 20 minutes of stimulation over the left fronto-temporal prefrontal cortex.<br>Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* Frequency of stimulation: 10Hz. Interstimulus interval: 1 min. Number of stimuli per session: 300. Number of sessions per week: 4 Total number of stimuli: 1.200<br>Device: Transcranial Direct Current Stimulation (SHAM)<br>* The electrodes of stimulation will be applied in the left fronto-temporal prefrontal cortex, but the device will be turned off.<br>Device: Repetitive Transcranial Magnetic Stimulation (SHAM)<br>* The coil will be applied on the left fronto-temporal prefrontal cortex, but the device will be turned off.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG coherence analysis | EEG will be filtered between 0.5 and 30Hz by elliptic filters. Fast Fourier Transformation will be performed on 2 sec-epochs. For each stimulation site, coherence values will be estimated within four frequency bands: Delta (0.5-3.5 Hz), Theta (4-7.5 Hz), Alpha (8-12.5 Hz), and Beta (13-30 Hz). Each coherence map will be proportionally thresholded, preserving 50% of the strongest coherence values, to produce a weighted adjacency matrix. The estimated functional connectivity patterns will be characterized by means of two global network metrics derived from graph theory: modularity and global efficiency. Modularity measures how the network is organized into modules with high level clustering. Global efficiency measures how efficient the network is in exchanging information at the global level. | Change from baseline EEG coherence at the end of brain stimulation (two weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability Rating Scale |  | Change from baseline DRS scale at the end of brain stimulation (two weeks) |