A New Objective Electrophysiological Technique As a Measure of Central Auditory Processing in a Rat Model of Autism Spectrum Disorder

Background: Gaps embedded in noise (GIN) have been used as acoustic stimulus to evaluate the auditory temporal processing of different study populations such as in subjects with central auditory processing disorders (CAPD). Since GIN are very short as miliseconds (ms), they have been used to evaluate temporal resolution which is defined as the ability to detect small changes in sound over time, or slight discontinuities in ongoing stimuli. Poor temporal resolution has been shown to correlate with speech recognition difficulties. The gap detection threshold (GDT) is defined as the shortest gap that can be perceived in an otherwise continuous background stimulus. Electrophysiological assessment of GIN has focused mainly on Late Latency Responses requiring awake alert subjects (humans or animals). As rat models are commonly employed to understand the molecular mechanisms underlying auditory and neurological disorders, there is a need to develop techniques to determine central auditory processing (CAP) in experimental animal models.

Objectives: One of the most commonly reported sensory processing impairments in individuals with autism spectrum disorder (ASD) is the abnormalities in CAP. ASD patients consistently exhibit atypical behaviors in response to auditory stimuli and CAPD, which refers to a complex and heterogeneous group of auditory-specific disorders. There is still not a reliable electrophysiological technique to determine CAPD in ASD patients. The aim of this study was to develop an electrophysiological technique that can be used as an objective measure of CAP in anesthetized rat model.

Methods: We developed a method to determine the Objective Gap Detection Threshold (OGDT) in rats. QSSR elicited by noise modulated by 40Hz gaps of different durations were analyzed in time and frequency domains using wild-type (WT) and rat model of ASD. The detection was performed in frequency domain, by applying the Hotelling’;s T2 test to the 40Hz complex fundamental frequency component. The OGDT is estimated by analyzing the confidence ellipses of the 40Hz spectral component.

Results: When the confidence ellipses (p=0.05) contain the origin of the complex plane, we observed that the subject is not significantly detecting the noise gap. We observed that the rats were detecting noise gaps of 12, 10 and 8ms and not detecting the 6ms gap. We also observed the “vanishing” of response into the background noise when a 4ms noise gap is applied. The 5ms OGDT result was verified by the statistical T2 test and is consistent with the previous animal studies with awake rats. The OGDT values were significantly increased in our rat model of ASD in agreement with findings observed in humans having ASD.

Conclusions: We have developed an electrophysiological method to determine GDT as a measure of CAPD in an anesthetized rat model. This technique eliminates the need for being alert and awake during the test bringing a new dimension especially in animal experiments regarding central auditory evaluation. The availability of novel objective techniques to determine CAPD will help in its early detection in patients diagnosed with ASD or suspicion of being on the spectrum leading to early intervention and hence better clinical outcomes.