Cortical auditory evoked potentials, brain signal variability and cognition as biomarkers to detect the presence of chronic tinnitus

Abstract

The current limited understanding of tinnitus neurophysiology is one of the major obstacles in developing effective treatments for chronic tinnitus. As such, there is an urgent need for knowledge on underlying neural and/or neurobehavioral correlates that might function as potential biomarkers for tinnitus. We aimed to develop a model for the detection of tinnitus cases based on such potential biomarkers. In a first step, data from twenty patients suffering from chronic tinnitus, but no concurrent hearing loss or psychological complaints, were compared to data from twenty matched controls. Cortical auditory evoked potentials (CAEP) were elicited using a standard oddball paradigm. Source estimation and brain signal variability were analyzed to investigate putative differences between tinnitus patients and controls. Other examinations included standard audiometry, speech understanding in quiet and noisy conditions, and cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The P300 component, a response to unexpected but relevant stimuli, was significantly reduced in the tinnitus group. Source estimation revealed that the response of tinnitus patients was characterized by a decreased activity in temporal cortex, parahippocampus and insula. Brain signal variability on fine time scales was significantly higher in the tinnitus group, suggesting that tinnitus patients rely more strongly on local information processing. Furthermore, tinnitus was associated with a decreased cognitive performance, especially on tasks measuring delayed memory. In a second step, a logistic regression model was constructed based on CAEP activity, brain signal variability and RBANS scores. This model performed significantly above chance level when detecting tinnitus cases in an unseen dataset (accuracy of 75%, area under the ROC curve of 0.86). The successful classification between tinnitus cases and controls demonstrates the potential value of the proposed combination of biomarkers. Moreover, the identified associations between tinnitus, auditory evoked activity and cognitive performance point towards a significant contribution of top-down information processing in the perception of tinnitus.