HD-tDCS Combined With Circadian Rhythm Reconstruction and Micro Expression Changes on Consciousness Recovery in Patients With Chronic Disturbance of Consciousness

Study Overview
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Brief Summary
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The circadian rhythm characteristics of sleep cycle and neuroendocrine in patients with chronic disorder of consciousness show different degrees of disorder, and the relationship between this disorder and consciousness level is unclear.The researchers used HD-tDCS to treat patients with chronic disturbance of consciousness who intervened in circadian rhythm, and used a variety of methods such as EEG, fMRI, protein metabolism, ERP and micro-expression to explore the mechanism of improving the state of consciousness of HD-DCS and the relationship between circadian rhythm and patients' consciousness level

Detailed Description
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The sleep status (> 24 hours) of patients with chronic disturbance of consciousness was recorded with the revised coma recovery scale revised (CRS-R) and Polysomnography (PSG). The sleep cycle of patients with chronic disturbance of consciousness was judged by the open and close eyes cycle and EEG. Patients with circadian rhythm treated with or without blue light stimulation and melatonin were treated with HD-tDCS. EEG, fMRI, protein metabolism, ERP and micro expression data were recorded before and after treatment.Explore the mechanism of improving the state of consciousness of HD-DCS and the relationship between circadian rhythm and patients' consciousness level

Official Title
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Effect and Mechanism of HD-tDCS Combined With Circadian Rhythm Remodeling on Consciousness Recovery in Patients With Chronic Disorder of Consciousness

Conditions
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Disorder of Consciousness

Intervention / Treatment
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* Drug: Melatonin
* Other: Placebo
* Other: HD-tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with diagnosis of disorder of consciousness Stable vital signs Good coordination, less spontaneous activity No anti-epileptic and sedative drugs taken within prior 24 hours The family members volunteered and signed the informed consent Exclusion Criteria: locked-in syndrome Diseases and factors that may affect the judgment of brain function, such as metabolic diseases, poisoning, shock, etc. There are contraindications to MRI scanning, such as the presence of metal implants in the body Contraindications treated by transcranial direct current stimulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tDCS and melatonin intervention<br>In real tDCS, the current was increased to 2 mA from the onset of stimulation and applied for 20 minutes. Participants were given a 3-mg fast-release oral dose of melatonin. | Drug: Melatonin<br>* Participants assigned to the melatonin group were given a 3-mg fast-release oral dose of melatonin administered at approximately 21:00<br>Other: HD-tDCS<br>* Direct current was applied using a battery-driven constant-current stimulator through saline-soaked surface sponge electrodes (7cm×5cm) with the anode placed over the left DLPFC (F3 according to the 10-20 international EEG system) and the reference cathode placed over the right supraorbital region (Fp2). During real tDCS, the current was increased to 2 mA from the onset of stimulation and applied for 20 minutes<br>|
| Experimental: tDCS intervention<br>In real tDCS, the current was increased to 2 mA from the onset of stimulation and applied for 20 minutes. | Other: Placebo<br>* Participants in this group were treated according to a protocol identical to those receiving active medication at approximately 21:00. For the sham tDCS groups, the same stimulation parameters were employed, except that the stimulator had a built-in placebo mode; when it was activated, two ramp fade-in/fade-out periods in the beginning and the end of sham stimulation mimicked the somatosensory artifact of real tDCS<br>Other: HD-tDCS<br>* Direct current was applied using a battery-driven constant-current stimulator through saline-soaked surface sponge electrodes (7cm×5cm) with the anode placed over the left DLPFC (F3 according to the 10-20 international EEG system) and the reference cathode placed over the right supraorbital region (Fp2). During real tDCS, the current was increased to 2 mA from the onset of stimulation and applied for 20 minutes<br>|
| Experimental: Melatonin intervention<br>Participants were given a 3-mg fast-release oral dose of melatonin. | Drug: Melatonin<br>* Participants assigned to the melatonin group were given a 3-mg fast-release oral dose of melatonin administered at approximately 21:00<br>|
| Placebo Comparator: Control<br>Patients were treated with the placebo and sham-tDCS. | Other: Placebo<br>* Participants in this group were treated according to a protocol identical to those receiving active medication at approximately 21:00. For the sham tDCS groups, the same stimulation parameters were employed, except that the stimulator had a built-in placebo mode; when it was activated, two ramp fade-in/fade-out periods in the beginning and the end of sham stimulation mimicked the somatosensory artifact of real tDCS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Coma Recovery Scale-Revised (CRS-R) scale | The CRS-R is a tool used to characterise the level of consciousness consisting of 23 hierarchically arranged items that comprise six subscales addressing the auditory, visual, motor, oromotor/verbal, communication and arousal processes. The values range from 0 to 23, with higher score indicating better outcome. | Change from Baseline CRS-R at 14 days. | 
| Electroencephalography (EEG) | Delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (12-30 Hz). An increase of delta and theta activity usually reflects encephalopathy and/or structural lesions, interpreted as poor outcome predictor of DOC .The power of α and β is related to the chance of recovery. | Change from baseline EEG power spectral density at 14 days. | 
| Sleep parameters | Changes in in sleep/wake architecture assessed by polysomnography. Electrodes attached to the scalp near the frontal, central (top) and occipital (back) portions of the brain and provide a readout of different stages of sleep (N1, N2, N3, REM, and Wakefulness). | Change from baseline sleep patterns at 14 days. | 
| Resting state fMRI | Resting state fMRI reflects the brain activity occured in a resting or task-negative state. Regional (ReHo, ALFF, fALFF, etc.) and global parameters (functional connectivity, etc.) could be used in this study. | Change from ReHo, ALFF, fALFF and functional connectivity at 14 days. | 
| Micro-expression | After listening to auditory stimulations, transient alterations may occur on the micro expression of the subjects. High-resolution video will be taken to capture each subject's facial micro-expressions while listening to the auditory materials. | At baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| protein metabolism | Changes of protein content in peripheral blood | Change from Baseline protein metabolism at 14 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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disorder of consciousness, Circadian rhythm, HD-tDCS