Auditory Processing in DOC Patients (AUD-DOC)

Hierarchical Auditory Processing in Disorders of Consciousness: From Basic Deviance Detection to Semantic Integration

This prospective observational study investigates whether electroencephalography (EEG) can improve the differentiation between unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) in patients with severe acquired brain injury. The study further examines the association between EEG markers of auditory processing and long-term functional outcome at 12 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Disorder of Consciousness; Minimally Conscious State; Unresponsive Wakefulness Syndrome
• Intervention / Treatment: Behavioral: Coma Recovery Scale-Revised (CRS-R); Behavioral: Electroencephalography (EEG)

Detailed Description

Accurate classification of disorders of consciousness remains challenging in neurological early rehabilitation. Behavioral assessment is the clinical standard, yet misclassification persists, particularly in patients with severe motor impairment or fluctuating arousal. Neurophysiological measures may provide complementary information beyond observable behavior.

This study applies event-related potential (ERP) paradigms during bedside EEG recording to assess hierarchical levels of auditory processing in patients with disorders of consciousness in the subacute phase after brain injury. The paradigms are designed to detect neural responses reflecting basic auditory discrimination as well as higher-order cognitive processing.

The primary objective is to determine the highest neurophysiologically detectable level of auditory processing and to examine whether it differs between clinically defined consciousness groups. Secondary objectives include evaluating the relationship between EEG-derived markers and standardized behavioral assessments, as well as assessing the prognostic value of EEG findings for functional outcome one year after admission.

The study aims to clarify the diagnostic and prognostic relevance of EEG-based measures in routine neurorehabilitation settings.

• Study Type: Observational
• Enrollment (Estimated): 42

Contacts and Locations

Study Locations

• Germany
  • Lower Saxony
    • Hessisch Oldendorf, Lower Saxony, Germany, 31840
      • BDH-Klinik Hessisch Oldendorf
      • Contact: Melanie Boltzmann, PhD; Phone Number: +49 5152781256; Email: m.boltzmann@bdh-klinik-hessisch-oldendorf.de
      • Contact: Simone B. Jenner; Phone Number: +49 5152781215; Email: s.jenner@bdh-klinik-hessisch-oldendorf.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population consists of adult patients (18-80 years) with severe acquired brain injury in the subacute phase who are diagnosed with a disorder of consciousness (Unresponsive Wakefulness Syndrome or Minimally Conscious State) in a neurological rehabilitation setting.

Description

Inclusion Criteria:

• Presence of a disorder of consciousness (Unresponsive Wakefulness Syndrome [UWS] or Minimally Conscious State [MCS]), classified using the Coma Recovery Scale-Revised (CRS-R) based on three assessments conducted on at least two separate days
• Age between 18 and 80 years
• Written informed consent provided by the patient's legal representative
• Preserved brainstem auditory evoked potentials (BAEPs) on at least one side

Exclusion Criteria:

• Ongoing sedation at the time of EEG assessment
• Current treatment with medications known to significantly affect cortical functional state, including barbiturates, neuroleptics (antipsychotics), antiepileptic drugs, benzodiazepines, or comparable agents
• Colonization with multidrug-resistant organisms requiring isolation precautions (e.g., 4MRGN)
• Pregnancy
• Impaired language comprehension (e.g., insufficient German language proficiency or aphasia)
• Temporal bone fractures or severe infratentorial brain injury associated with unilateral or bilateral absence of auditory evoked potentials (AEPs)
• Bilateral hearing impairment or deafness, or presence of a cochlear implant
• Scalp wounds or conditions preventing placement of an EEG electrode cap

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
UWS patients; Patients classified as unresponsive wakefulness syndrome (UWS) with the Coma Recovery Scale-Revised (CRS-R)	Behavioral: Coma Recovery Scale-Revised (CRS-R); The Coma Recovery Scale-Revised (CRS-R) is a standardized behavioral assessment instrument used to determine the level of consciousness in patients with severe brain injury. It comprises six subscales evaluating auditory, visual, motor, oromotor/verbal, communication, and arousal functions, with hierarchically structured items to identify the highest level of behavioral responsiveness.; Behavioral: Electroencephalography (EEG); Electroencephalography (EEG) is a non-invasive neurophysiological method used to record spontaneous and stimulus-related electrical brain activity via scalp electrodes. In this study, bedside EEG recordings are performed using structured auditory stimulation paradigms designed to elicit event-related potentials (ERPs). These include hierarchical paradigms assessing different levels of auditory processing, ranging from basic sensory discrimination (e.g., mismatch negativity, MMN) to higher-order cognitive processing (e.g., N400 responses). EEG-derived ERP markers are analyzed to determine the highest detectable level of auditory processing and to evaluate their association with clinical diagnosis and long-term functional outcome.
MCS patients; Patients classified as minimally conscious state (MCS) with the Coma Recovery Scale-Revised (CRS-R)	Behavioral: Coma Recovery Scale-Revised (CRS-R); The Coma Recovery Scale-Revised (CRS-R) is a standardized behavioral assessment instrument used to determine the level of consciousness in patients with severe brain injury. It comprises six subscales evaluating auditory, visual, motor, oromotor/verbal, communication, and arousal functions, with hierarchically structured items to identify the highest level of behavioral responsiveness.; Behavioral: Electroencephalography (EEG); Electroencephalography (EEG) is a non-invasive neurophysiological method used to record spontaneous and stimulus-related electrical brain activity via scalp electrodes. In this study, bedside EEG recordings are performed using structured auditory stimulation paradigms designed to elicit event-related potentials (ERPs). These include hierarchical paradigms assessing different levels of auditory processing, ranging from basic sensory discrimination (e.g., mismatch negativity, MMN) to higher-order cognitive processing (e.g., N400 responses). EEG-derived ERP markers are analyzed to determine the highest detectable level of auditory processing and to evaluate their association with clinical diagnosis and long-term functional outcome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Highest Detectable Hierarchical Level of Auditory Processing	The primary endpoint is the highest neurophysiologically detectable hierarchical level of auditory processing, operationalized by the presence of significant auditory event-related potential (ERP) effects. For each ERP paradigm, analyses are conducted at the individual patient level to determine whether a statistically significant ERP effect is present within predefined time windows and electrode regions. The highest hierarchy level showing a significant effect defines the individual outcome (ordinal scale: levels 1-4).	week 2-3 after admission to neurological rehabilitation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between Clinical Level of Consciousness and Neurophysiological Cognitive Processing	Relationship between clinically determined consciousness status (e.g., UWS vs. MCS) and the highest achieved hierarchical level of auditory processing as measured by ERP responses.	week 2-3 after admission to neurological rehabilitation
Prognostic Validity of ERP-Based Hierarchical Processing Level	Predictive value of the highest achieved hierarchical level of auditory processing for functional outcome at 12 months after admission. Functional status will be assessed using a standardized outcome measure.	12 months after EEG measurement

Collaborators and Investigators

• Sponsor: BDH-Klinik Hessisch Oldendorf

Publications and helpful links

General Publications

• Cruse D, Chennu S, Chatelle C, Bekinschtein TA, Fernandez-Espejo D, Pickard JD, Laureys S, Owen AM. Bedside detection of awareness in the vegetative state: a cohort study. Lancet. 2011 Dec 17;378(9809):2088-94. doi: 10.1016/S0140-6736(11)61224-5. Epub 2011 Nov 9.
• Wannez S, Heine L, Thonnard M, Gosseries O, Laureys S; Coma Science Group collaborators. The repetition of behavioral assessments in diagnosis of disorders of consciousness. Ann Neurol. 2017 Jun;81(6):883-889. doi: 10.1002/ana.24962.
• Engemann DA, Raimondo F, King JR, Rohaut B, Louppe G, Faugeras F, Annen J, Cassol H, Gosseries O, Fernandez-Slezak D, Laureys S, Naccache L, Dehaene S, Sitt JD. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain. 2018 Nov 1;141(11):3179-3192. doi: 10.1093/brain/awy251.
• Kondziella D, Bender A, Diserens K, van Erp W, Estraneo A, Formisano R, Laureys S, Naccache L, Ozturk S, Rohaut B, Sitt JD, Stender J, Tiainen M, Rossetti AO, Gosseries O, Chatelle C; EAN Panel on Coma, Disorders of Consciousness. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness. Eur J Neurol. 2020 May;27(5):741-756. doi: 10.1111/ene.14151. Epub 2020 Feb 23.
• Young MJ, Bodien YG, Giacino JT, Fins JJ, Truog RD, Hochberg LR, Edlow BL. The neuroethics of disorders of consciousness: a brief history of evolving ideas. Brain. 2021 Dec 16;144(11):3291-3310. doi: 10.1093/brain/awab290.
• Kotchoubey B. Event-related potential measures of consciousness: two equations with three unknowns. Prog Brain Res. 2005;150:427-44. doi: 10.1016/S0079-6123(05)50030-X.

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Critically ill patients; Disorders of Consciousness; Electroencephalography (EEG); Acquired Brain Injury; Neurological rehabilitation; Event-related potential (ERP); Coma Recovery Scale-Revised (CRS-R)
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Neurobehavioral Manifestations; Neurocognitive Disorders; Craniocerebral Trauma; Trauma, Nervous System; Brain Damage, Chronic; Unconsciousness; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Brain Injuries; Consciousness Disorders; Persistent Vegetative State
• Other Study ID Numbers: AUD-DOC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No