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The aim of this project is to investigate whether tickling stimulations can have a short-term effect on the responsiveness of patients with Disorders of Consciousness due to Severe Acquired Brain Injury and to compare this effect with that of neutral tactile stimulations that do not induce tickling.
During the experimental session, patients will undergo the CRS-R and the Nociception Coma Scale-Revised (NCS-R) to ensure that any responses to tickling are not influenced by pain sensations. Subsequently, fNIRS detection optodes will be placed using a non-invasive frontal headband. A 10-minute resting-state recording will be performed. Next, patients will be subjected to tickling: they will be tickled bilaterally in the three most ticklish areas identified in a pilot study with healthy subjects-namely, the soles of the feet, the armpits, and the ribs-plus a control area, the forehead. The stimulation will be manual and will be performed by rubbing the targeted body part while opening and closing fingers in pairs in an arched motion. Additionally, patients will also receive a neutral stimulation (in the same body areas), which consists of simply touching the area without inducing tickling. The order of stimulations will follow a randomized list. Each stimulation will last for 5 seconds, followed by 5 seconds of rest, repeated twice. In total, patients will be stimulated for 10 seconds plus 5 seconds of rest (15 seconds in total) for each body area. There will be a 1-minute pause between each area. Afterward, an additional 10 minute resting-state fNIRS recording will be conducted. During the experimental session, patients will be filmed so that the videos can be analyzed by two different experimenters, who will assess differences between stimulations based on facial expressions, verbalizations/vocalizations, body movements, and changes in emotional state (e.g., crying, smiling, grimacing). At the end of the protocol, the fNIRS optodes will be removed. In total, the experiment will last approximately one hour and fifteen minutes: 30 minutes for CRS-R/NCS-R and 45 minutes for the tickling protocol and fNIRS recording.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with Disorders of Consciousness (DoC) | All patients with disorders of consciousness who are consecutively admitted to the participating centers of the study will be enrolled with a diagnosis of disorders of consciousness based on the CRS-R scale, with an age ≥18 years and a time since the event ≥ 28 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tickle stimulation | Behavioral | Patients will be subjected to tickling: they will be tickled bilaterally in three areas, the soles of the feet, the armpits, and the ribs-plus a control area, the forehead. The stimulation will be manual and performed by rubbing the targeted body part while opening and closing the fingers in pairs in an arched motion. Additionally, patients will also undergo a neutral stimulation (in the same body areas), which consists of simply touching the area without inducing tickling. |
| Measure | Description | Time Frame |
|---|---|---|
| Behavioral Response Scores During Tickling and Neutral Stimulation (Video Coding) | Behavioral responses will be evaluated from video recordings by two blinded raters, based on predefined observational categories (e.g., facial expressions, vocalizations, etc). | Day 1 (single session) |
| Hemodynamic Response Changes Measured by fNIRS During Tickling and Neutral Stimulation | Oxygenated and deoxygenated hemoglobin changes (HbO/HbR) will be recorded using functional near-infrared spectroscopy (fNIRS) in response to tactile stimulation. Signal changes in prefrontal regions will be analyzed and compared across stimulation types. | Day 1 (single session) |
| Cortical EEG Activation Patterns During Tickling and Neutral Stimulation (SedLine) | EEG data will be acquired with SedLine during stimulation sessions. Spectral power in defined frequency bands (e.g., alpha, beta) will be analyzed and compared between conditions. | Day 1 (single session) |
| Measure | Description | Time Frame |
|---|---|---|
| Coma Recovery Scale-Revised (CRS-R) Total Score Prior to Tickling Stimulation | Coma Recovery Scale-Revised (CRS-R) total score assessed before the stimulation protocol to determine baseline level of consciousness.The Coma Recovery Scale-Revised (CRS-R) is a standardized behavioral assessment tool used to determine the level of consciousness in patients with disorders of consciousness. Scores range from 0 to 23, with higher scores indicating better consciousness and functional responsiveness. |
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Inclusion Criteria:
Exclusion Criteria:
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All patients with DoC who are consecutively admitted to the participating centers of the study.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Simona Abagnale, PhD | Contact | +393487520258 | sabagnale@dongnocchi.it |
| Name | Affiliation | Role |
|---|---|---|
| Anna Estraneo, MD | Fondazione Don Gnocchi | Principal Investigator |
| Olivia Gosseries, PhD, Professor | University of Liege | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Coma Science Group - University of Liege | Completed | Liège | Belgium | 4000 | Belgium | |
IPD collected throughout the trial (CRS-R, NCS-R, video recordings outcomes, fNIRS data)
From the first patient recording data until the last patient.
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| ID | Term |
|---|---|
| D003244 | Consciousness Disorders |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D064926 | Neurophysiological Monitoring |
| ID | Term |
|---|---|
| D008991 | Monitoring, Physiologic |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Neurophysiological Monitoring with SedLine | Device | SedLine is a portable, non-invasive EEG monitoring device used to record electrical brain activity through frontal electrodes. In the TICKLING-DOC study, SedLine is used to assess cortical responses in patients with disorders of consciousness (DoC) during manual tactile stimulation, specifically tickling, and neutral touch. The EEG data are recorded before, during, and after stimulation to detect neural reactivity and possible correlations with behavioral responses. The goal is to investigate whether tickle-evoked EEG activity reflects residual consciousness and contributes to diagnostic and rehabilitative strategies. SedLine allows continuous monitoring in a bedside setting, offering safe, real-time assessment of brain function. |
|
|
| Day 1 (baseline) |
| Nociception Coma Scale-Revised (NCS-R) Total Score Prior to Stimulation | NCS-R will be administered before tactile stimulations to assess nociceptive reactivity. The Nociception Coma Scale-Revised (NCS-R) is a standardised behavioural tool used to assess nociceptive responses in patients with disorders of consciousness. It includes three subscales (motor, verbal, and facial responses). Scores range from 0 to 9, with higher scores indicating greater responsiveness to nociceptive stimuli. | Day 1 (baseline) |
| Fondazione Don Gnocchi |
| Recruiting |
| Sant'Angelo dei Lombardi |
| Avellino |
| 83054 |
| Italy |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |