Potential Audiological and MRI Markers of Tinnitus.

BACKGROUND: Subjective tinnitus, or ringing sensation in the ear, is a common disorder with no accepted objective diagnostic markers. PURPOSE: The purpose of this study was to identify possible objective markers of tinnitus by combining audiological and imaging-based techniques. RESEARCH DESIGN: Case-control studies. STUDY SAMPLE: Twenty adults drawn from our audiology clinic served as participants. The tinnitus group consisted of ten participants with chronic bilateral constant tinnitus, and the control group consisted of ten participants with no history of tinnitus. Each participant with tinnitus was closely matched with a control participant on the basis of age, gender, and hearing thresholds. DATA COLLECTION AND ANALYSES: Data acquisition focused on systematic administration and evaluation of various audiological tests, including auditory-evoked potentials (AEP) and otoacoustic emissions, and magnetic resonance imaging (MRI) tests. A total of 14 objective test measures (predictors) obtained from audiological and MRI tests were subjected to statistical analyses to identify the best predictors of tinnitus group membership. The least absolute shrinkage and selection operator technique for feature extraction, supplemented by the leave-one-out cross-validation technique, were used to extract the best predictors. This approach provided a conservative model that was highly regularized with its error within 1 standard error of the minimum. RESULTS: The model selected increased frontal cortex (FC) functional MRI activity to pure tones matching their respective tinnitus pitch, and augmented AEP wave N1 amplitude growth in the tinnitus group as the top two predictors of tinnitus group membership. These findings suggest that the amplified responses to acoustic signals and hyperactivity in attention regions of the brain may be a result of overattention among individuals that experience chronic tinnitus. CONCLUSIONS: These results suggest that increased functional MRI activity in the FC to sounds and augmented N1 amplitude growth may potentially be the objective diagnostic indicators of tinnitus. However, due to the small sample size and lack of subgroups within the tinnitus population in this study, more research is needed before generalizing these findings.

An in vitro model for testing drugs to treat tinnitus.

Tinnitus affects approximately 50 million people in the USA alone, with 10 million being highly debilitated. Pharmacotherapy for tinnitus is still in emerging stages due to time consuming clinical trials and/or animal experiments. We tested a new cellular model where induced rapid neuronal firing or spiking was used as a mimic for the type of aberrant activity that may occur in tinnitus. Spontaneously active auditory cortical networks growing on microelectrode arrays were exposed to pentylenetetrazol (PTZ), a proconvulsant and an antagonist of GABA(A) receptor, which is implicated in tinnitus. Auditory cortical networks were then exposed to experimental tinnitus drugs linopirdine (Dup966, a potassium channel blocker), L-carnitine (an antioxidant), or selective Ca(2+) channel antagonists pregabalin (Lyrica), or gabapentin (Neurontin) at various concentrations. PTZ increased spike rate by 139.6±27% and burst rate by 129.7±28% in auditory cortical networks with a phenotypic high firing of excitable neurons. Reductions of increased activity were observed to varying degrees using the experimental tinnitus drugs. The potency of the drugs was linopirdine (EC(50): 176±7.0 µM)>L-carnitine (EC(50): 1569±41 µM)>pregabalin (EC(50): 8360±340 µM), >gabapentin, with 34.2±7.5% efficacy (EC(50): 2092±980 µM). These studies provide proof of principle for the use of auditory cortical networks on microelectrode array as a feasible platform for semi-high throughput application for screening of drugs that might be used for the treatment of tinnitus.