Spontaneous Eye Blinking Evaluation for Cognitive Assessment of Individuals With Severe Acquired Brain Injury (SEE-ABI)

Assessment of consciousness and attention in individuals with severe Acquired Brain Injury (sABI) is crucial for planning rehabilitation, but it is often hindered by coexisting sensory-motor and/or cognitive-behavioural disorders.

This project aims at evaluating the value of spontaneous eye blinking features to assess patients' attentional abilities and to distinguish patients with unresponsive wakefulness syndrome (UWS) from those in minimally conscious state (MCS).

Patients will undergo an EEG-EOG recording at rest and during an auditory oddball task. Eye blinking features on EOG will be analysed and compared to that of healthy individuals. A machine-learning-based algorithm using blinking features for the diagnosis of patients with sABI will be studied and validated preliminarily.

This project will help to stratify patients with sABI using easy-to-detect clinical markers, supporting clinicians' decision-making about patient's management. Additionally, blinking patterns related to residual attentional abilities in patients emerged from disorders of consciousness will be investigated.

Study Overview

• Status: Active, not recruiting
• Conditions: Acquired Brain Injury; Disorders of Consciousness
• Intervention / Treatment: Diagnostic test: EEG-EOG recording at rest and during an auditory oddball paradigm

Detailed Description

Overall aim: to provide preliminary results on the value of spontaneous eye blinking features (i.e., rate, amplitude, duration, and variability in intervals between blinks), which do not rely on voluntary behavioural responses, for improving the assessment of attentional abilities and consciousness in patients with sABI.

Specific aims:

1. to confirm the diagnostic value of EBR in pDoC patients, as in Magliacano et al.'s (2021) study;
2. to improve diagnostic accuracy of patients with prolonged Disorders of Consciousness (pDoC) by evaluating additional blinking features (i.e., amplitude, duration, variability in intervals between blinks) for discriminating patients in UWS from those in MCS or conscious.
3. to explore the usefulness of eye blinking features analysis for assessing residual attentional abilities in full-conscious patients recovering from pDoC.
4. prototyping a machine-learning-enabled pipeline for supporting consciousness diagnosis based on Eye Blink Rate (EBR) and EOG-derived features. The interpretability and reliability aspects will be carefully evaluated to obtain a clinically usable solution for supporting diagnostic procedures and planning tailored cognitive rehabilitation.

Overall, this study is proposing a preliminary investigation, with pilot samples of both healthy and test population, for the analysis of EBR and EOG-derived biomarkers. These results will lay the foundations for the development and validation of multifactorial decisional algorithms for patients' diagnostic and prognostic stratification, based on easily collectable clinical markers.

This project has an observational, cross-sectional design. All patients with sABI consecutively admitted will be screened. We plan to enrol a convenience test sample of 35 patients with sABI including 10 patients with pDoC (5 in UWS, 5 in MCS) and 25 patients who recovered full consciousness after sABI.

A benchmark population of 20 healthy individuals, balanced for age and sex with the patient sample, will be also enrolled, by means of word-of-mouth according to a snowball sampling. This population will undergo anamnestic interview, and neurological and primary cognitive examination for excluding history or presence of neurological disorders. At study entry, patients' demographic (e.g., age, sex), anamnestic (e.g., aetiology, time post-injury, brain lesion location), and clinical data will be collected. Patients' clinical diagnosis and cognitive functioning will be classified according to their best score on the repeated Coma Recovery Scale-Revised (CRS-R) and on Levels of Cognitive Functioning (LCF), respectively.

Within 2 weeks from study entry, each patient will attend an electroencephalogram-electrooculogram (EEG-EOG) recording session. Eye blinking will be examined during a rest condition (duration: 8 min) and during an active auditory oddball task (duration: 8 min), consisting of randomly intermixed tones (non-target: 500 Hz, overall probability: 80%, n=312; target: 1000 Hz, overall probability: 20%, n=78) presented with a 1-s inter-stimulus interval through headphones. To complement clinical assessment, the background activity on resting EEG and the presence of the P300 component on event-related potentials following the auditory oddball paradigm will be evaluated. Patients' consciousness (CRS-R) and cognitive functioning (LCF) levels will be gathered on the day of the EEG-EOG recording session, and considered for statistical analysis.

Control participants will undergo the same EEG-EOG recording as the patients. For both participant groups, blinks will be defined as a sharp positive peak followed by a shallow negative deflection in a time window of <400 ms on the EOG. Moreover, to prevent awareness of blink recording affects blink features, throughout recording sessions participants will be never informed of the blinking recording, but they will be encouraged to stay relaxed with their eyes open. This procedure will be conducted regardless of the participant (patient or control) group.

Biostatistical analyses will be exploited for the investigation of associations between EOG-derived biomarkers and residual attentional abilities in conscious sABI patients under different acquisition paradigms, in response to Objective 3. Objective 4 will be addressed through the development of Machine Learning-based prototypes for the diagnosis of patients with pDoC using information derived from EOG signals, complemented by EEG and clinical data. The interpretability and error analyses will pose the premises for the identification of eventual covert patterns contained in EOG data.

• Study Type: Observational
• Enrollment (Estimated): 55

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy
    • IRCCS Fondazione Don Carlo Gnocchi Firenze
  • AV
    • Sant'Angelo dei Lombardi, AV, Italy, 83054
      • Polo Specialistico Riabilitativo Fondazione Don Carlo Gnocchi ONLUS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients with sABI consecutively admitted will be screened.

Description

Inclusion Criteria:

• diagnosis of severe acquired brain injury;
• age≥18 years;
• time post-injury≥28 days
• written informed consent by patient or, where necessary, by primary caregiver

Exclusion criteria will be:

• large craniectomy interfering with EEG recording;
• unstable clinical conditions;
• presence of ophthalmic disorders, or central or peripheral impairments in eyelid motility on clinical evaluation;
• administration of sedative medication in the previous 24h;
• previous history of neurological or psychiatric diseases

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with severe acquired brain injury; Patients' inclusion criteria: (i) age≥18 years; (ii) time post-injury≥28 days. Exclusion criteria will be: (i) large craniectomy interfering with EEG recording; (ii) unstable clinical conditions; (iii) presence of ophthalmic disorders, or central or peripheral impairments in eyelid motility on clinical evaluation; (iv) administration of sedative medication in the previous 24h; (v) previous history of neurological or psychiatric diseases; (vi) written informed consent by patient or, where necessary, by primary caregiver.	Diagnostic test: EEG-EOG recording at rest and during an auditory oddball paradigm; Participants will attend an electroencephalogram-electrooculogram (EEG-EOG) recording session. Eye blinking will be examined during a rest condition (duration: 8 min) and during an active auditory oddball task (duration: 8 min), consisting of randomly intermixed tones (non-target: 500 Hz, overall probability: 80%, n=312; target: 1000 Hz, overall probability: 20%, n=78) presented with a 1-s inter-stimulus interval through headphones.
Benchmark sample; i) age≥18 years; ii) normal or corrected-to-normal vision excluding contact lenses; iii) a total score >22.23 at the Montreal Cognitive Assessment (Santangelo et al., 2015); iv) written informed consent. Exclusion criteria: i) presence of ophthalmic disorders, or central or peripheral impairments in eyelid motility on clinical evaluation; ii) consumption of drugs acting on the central nervous system; iii) previous history of neurologic or psychiatric diseases.	Diagnostic test: EEG-EOG recording at rest and during an auditory oddball paradigm; Participants will attend an electroencephalogram-electrooculogram (EEG-EOG) recording session. Eye blinking will be examined during a rest condition (duration: 8 min) and during an active auditory oddball task (duration: 8 min), consisting of randomly intermixed tones (non-target: 500 Hz, overall probability: 80%, n=312; target: 1000 Hz, overall probability: 20%, n=78) presented with a 1-s inter-stimulus interval through headphones.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coma Recovery Scale-Revised	The Coma Recovery Scale-Revised is a clinical scale with a total score ranging from 0 to 23, with higher scores indicating a higher level of consciousness	Within 2 weeks from study entry
Levels of Cognitive Functioning	Levels of Cognitive Functioning is a clinical scale with a score ranging from 1 to 8, with higher scores indicating a higher level of cognitive functioning	Within 2 weeks from study entry

Collaborators and Investigators

• Sponsor: Alfonso Magliacano

Publications and helpful links

General Publications

• Magliacano A, Rosenfelder M, Hieber N, Bender A, Estraneo A, Trojano L. Spontaneous eye blinking as a diagnostic marker in prolonged disorders of consciousness. Sci Rep. 2021 Nov 17;11(1):22393. doi: 10.1038/s41598-021-01858-3.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2025
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: machine learning; cognitive rehabilitation; diagnosis; severe acquired brain injury; eye blinking
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Pathologic Processes; Neurobehavioral Manifestations; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Disease; Brain Injuries; Consciousness Disorders
• Other Study ID Numbers: SEE-ABI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No