Pathophysiology, Psycho-emotional and Cognitive Functioning Associated With Tinnitus (AudiCog)

Cognitive and Emotional Function and Brain Reorganisation Associated to Auditory Abilities : Impact of Tinnitus

the investigators have recently shown that patients with drug-resistant temporal lobe epilepsy who have undergone brain surgery targeting the medial temporal lobe structures were more likely to develop tinnitus postoperatively. This discovery of a vulnerability to tinnitus associated with medial temporal lobe surgery to eliminate drug-refractory epileptic seizures provides a new clinical model of tinnitus, targeting temporal lobe regions as generators or mediators of this hearing disorder. The objective of this project is to study the impact of tinnitus on the cognitive, emotional, psychoacoustic and cerebral functioning associated with this hearing disorder, and to clarify the pathophysiology of tinnitus by comparing different groups of individuals with tinnitus (surgical epileptic patients or non-surgical ORL patients) to matched tinnitus-free groups (surgical tinnitus-free cases and healthy controls volunteer).

Study Overview

• Status: Recruiting
• Conditions: Tinnitus; Epilepsy, Temporal Lobe
• Intervention / Treatment: Other: acoustics tests, Questionaries,; Radiation: MRI

Detailed Description

Tinnitus (known as "ringing in the ears") is a disabling medical condition. Its psychosocial impact is substantial, including anxiety, depression, stress, irritability, concentration and sleep disorder leading to detrimental effects on communication, education, professional fulfillment, mental health and quality of life. The cerebral bases of tinnitus and its consequence on human hearing health have received a lot of attention in the scientific literature. Yet, the relationship between the neurobiological dysfunction, psychological processes and clinical semiology of tinnitus remains poorly understood. Considering the current gaps in knowledge, there is a real need for clinical investigations into tinnitus-related brain changes and rigorous hearing, psycho-emotional, and cognitive assessments. the investigators recent discovery of a vulnerability to tinnitus associated with medial temporal lobe surgery (to treat refractory epilepsy) provides a new clinical model, which targets the temporal lobe regions as a tinnitus generator or mediator of its severity. The goal of this collaborative interdisciplinary study is to advance knowledge about the pathophysiology of tinnitus, as well as the socio-emotional, cognitive and psychoacoustic aspects associated to this hearing disorder. the investigators will first, characterize the subjective and self-reported hearing disorders with objective psychoacoustic, cognitive and affective measures in tinnitus sufferers and second, clarify the cerebral network underlying tinnitus and elucidate the role temporal lobe regions in the brain networks at play in surgical and non-surgical tinnitus. To this end, individuals with and without tinnitus, who had undergone or not a surgery will be compared in a 2 by 2 design. Investigating different patient cohorts with tinnitus who are well matched to both, healthy control populations and vulnerable clinical populations, without tinnitus is a valuable contribution of our proposal. Moreover, the psychological and hearing profiles of people with tinnitus will be examined in relation with their brain morphology and connectivity profiles.The project builds upon the internationally recognized leadership of the PI and her collaborators in the fields of auditory cognition and its neurobiological bases using neuropsychological, psychoacoustic, and neuroimaging methods in clinical populations. The members of the investigators consortium have all the necessary and unique expertise to carry out this innovative and interdisciplinary project.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie DUPONT, MD, Ph.D; Phone Number: 01 42 16 03 01; Email: sophie.dupont@aphp.fr
• Study Contact Backup: Name: Séverine Samson, Ph.D; Phone Number: 03 20 41 64 43; Email: severine.samson@univ-lille.fr

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital Européen Georges Pompidou
    • Contact: Alain LONDERO; Phone Number: 01 56 09 34 79; Email: alain.londero@aphp.fr
  • Paris, France, 75013
    • Recruiting
    • Service de Soins de Suite et Réadaptation (SSR) Neurologique, DMU de Neurosciences
    • Contact: Sophie DUPONT, MD, Ph.D; Phone Number: 01 42 16 03 01; Email: sophie.dupont@aphp.fr
    • Contact: Séverine Samson, Ph.D; Phone Number: 03 20 41 64 43; Email: severine.samson@univ-lille.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Common Criteria for Inclusion :

• Age ≥ 18 years old
• Good written and oral comprehension of the French language
• Person affiliated to a Social Security scheme
• Informed consent signed by the participant
• Normal or corrected vision
• Absence of known pre-existing neurological and/or degenerative disorders

Group Specific Inclusion Criteria :

Tinnitus+ Group - Suffering from subjective uni- or bilateral tinnitus, chronic (>3 months) and stable (no period of remission).

Chir+ Group

- Surgically treated for drug-resistant epilepsy of the temporal lobe (including the amygdala).

Group Tinnitus-

• Not suffering from tinnitus Group Chir-
• Non epileptic
• Not having undergone surgical treatment of the temporal lobe (including the tonsil)

Exclusion criteria:

• Presence of severe or profound deafness, uni or bilateral.
• Under legal protection (guardianship, curators, etc.)

Additional criteria for patients completing visit V2 :

• MRI contraindicated or claustrophobic
• Pregnant or breastfeeding woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: impact of tinnitus on executive cognitive functioning	Other: acoustics tests, Questionaries,; acoustics tests at V1 Questionaries at V1; cognitive; emotional; auditory
Experimental: impact of tinnitus on reorganization of functional/ structural brain connectivity maps	Other: acoustics tests, Questionaries,; acoustics tests at V1 Questionaries at V1; cognitive; emotional; auditory; Radiation: MRI; Anatomical and functional MRI at V2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the impact of tinnitus on executive cognitive functioning	Measurement of executive control using a stroop test in people with and without chronic tinnitus.	at the second visit, maximum 6 month after first visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emotional functioning (anxiety and depression)	Measures of Anxiety and Depression using: Hospital Anxiety and Depression Scale (HADS) : 14 rated items from 0 to 3. Seven questions are related to anxiety and seven to the depressive dimension, allowing for thus obtaining two scores (maximum score of each score = 21).	at the second visit, maximum 6 month after first visit.
psycho-acoustic functioning	Measurements of auditory functioning through hearing assessment (audiometry) : - Self-assessment questionnaires for hearing loss: The self-assessment of hearing loss is based on a yes/no question: "Do you feel that you have a hearing loss or hearing loss?	at the second visit, maximum 6 month after first visit.
psycho-acoustic functioning	Measurements of auditory functioning through hearing assessment (audiometry) : - The noise hypersensitivity questionnaire( Khalfa, 2002) provides a score ranging from 0 (no hypersensitivity) to 42 (very strong hypersensitivity).	at the second visit, maximum 6 month after first visit.
psycho-acoustic functioning	Measurements of auditory functioning through hearing assessment (audiometry) : - The severity of tinnitus is measured by the Tinnitus Handicap Inventory (THI) questionnaire. Scores range from 0 (mild discomfort) to 100 (catastrophic impact).	at the second visit, maximum 6 month after first visit.
psycho-acoustic functioning	Measurements of auditory functioning through hearing assessment (audiometry) : - Hearing threshold measurement (pure tones from 125-16000Hz)	at the second visit, maximum 6 month after first visit.
psycho-acoustic functioning	Measurements of auditory functioning through hearing assessment (audiometry) : - Discomfort threshold measurement (with 1kHz sound)	at the second visit, maximum 6 month after first visit.
psycho-acoustic functioning	Measurements of auditory functioning through hearing assessment (audiometry) : Evaluation of transient otoacoustic emissions (TEOAE) or by distortion product (DPOAE)	at the second visit, maximum 6 month after first visit.
cognitive functioning, other than executive functioning (attention, memory)	Measures of cognitive functioning : - the Attentional Network Test (ANT) visual attention test. ANT gives three attention scores based on reaction times. These scores represent the ability to direct attention, to be alert to surrounding stimuli and the executive part of attention.	at the second visit, maximum 6 month after first visit.
cognitive functioning, other than executive functioning (attention, memory)	Measures of cognitive functioning : - Mental Flexibility Score (Trail Making Test): The scores of the TMT (Trail Making Test) are expressed in time of completion. The faster the time to completion, the better the performance. So we have 2 scores, one for board A of the test: TMT-A and the other for board B of the test: TMT-B.	at the second visit, maximum 6 month after first visit.
cognitive functioning, other than executive functioning (attention, memory)	Measures of cognitive functioning : Measures of cognitive functioning :- Short-term memory score (auditive-verbal span). Score between 1 and 10, where 10 represents the best short-term memory score	at the second visit, maximum 6 month after first visit.
cognitive functioning, other than executive functioning (attention, memory)	Measures of cognitive functioning : Measures of cognitive functioning :- Working memory score (Brown-Peterson). The Brown Peterson gives a memorization score ranging from 0 to 100, where 100% is the best score.	at the second visit, maximum 6 month after first visit.
cognitive functioning, other than executive functioning (attention, memory)	Measures of cognitive functioning : - Episodic memory score in auditory modality. The episodic memory test in auditory mode gives a memorization score ranging from 0 to 100, where 100% represents a perfect memorization score.	at the second visit, maximum 6 month after first visit.
the reorganization of functional and structural brain connectivity maps	Functional and structural brain connectivity measurements using brain imaging (fMRI, diffusion and resting MRI) : - Volumetric measurement (in particular of the amygdala and the parahippocampal cortex)	at the third visit, maximum 18 month after the first visit
the reorganization of functional and structural brain connectivity maps	Functional and structural brain connectivity measurements using brain imaging (fMRI, diffusion and resting MRI) : - Measurement of anatomical connections between regions of interest (i.e. amygdala, auditory cortex, attention network including the precuneus and prefrontal cortex) from diffusion tensor imaging (TDI): fractional anisotropy (FA), mean diffusivity (MD), radial (RD) and axial (AD).	at the third visit, maximum 18 month after the first visit
the reorganization of functional and structural brain connectivity maps	Functional and structural brain connectivity measurements using brain imaging (fMRI, diffusion and resting MRI) : - Measurement of structural connectivity from fMRI at rest between predefined regions of interest and over new regions of interest defined during an attentional activation task	at the third visit, maximum 18 month after the first visit
the reorganization of functional and structural brain connectivity maps	Functional and structural brain connectivity measurements using brain imaging (fMRI, diffusion and resting MRI) : - Measurement of the amplitude of the synchrony of slow fluctuations and statistical dependencies in functional connectivity by comparing data from people with and without chronic tinnitus.	at the third visit, maximum 18 month after the first visit
Emotional functioning (stress)	Measures of stress using Perceived Stress Scale (PSS-4): Lowest score: 0, Highest score: 16, Higher scores are correlated to more stress.	at the second visit, maximum 6 month after first visit.
Emotional functioning (Auditory recognition of emotions)	Measures of Auditory recognition of emotions using hearing tests with recordings	at the second visit, maximum 6 month after first visit.

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Sophie Dupont, MD, Ph.D, AP-HP Hopital Pitie-Salpetriere

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): April 15, 2029

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Epilepsy; Tinnitus; Brain connectivity; Cognitive Functioning
• Additional Relevant MeSH Terms: Epileptic Syndromes; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Epilepsies, Partial; Epilepsy; Epilepsy, Temporal Lobe; Tinnitus
• Other Study ID Numbers: APHP200761

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