Development of Effective Strategies for Tinnitus Diagnosis and Treatment

Research Trainee: Aaron Apawu, PhD, Postdoctoral Fellow, Dept. of Anatomy and Call Biology at Wayne State University

Faculty Sponsor: Avril Genene Holt, PhD, Associate Professor of Anatomy and Cell Biology at Wayne State University

Animals exposed to unilateral acoustic trauma demonstrated significant deficits in gap detection ability at 20 kHz frequency and 45 dB intensity, in comparison to non-noise exposed animals, one month after noise exposure (p=.05). Two months following noise exposure, animals demonstrated marginally significant deficits in gap detection (p=.08) in comparison to controls. This decrease in gap detection resulted in decreased suppression of the acoustic startle response. TTS= temporary threshold shift induced by mild noise exposure

Animals exposed to unilateral acoustic trauma demonstrated significant deficits in gap detection ability at 20 kHz frequency and 45 dB intensity, in comparison to non-noise exposed animals, one month after noise exposure (p=.05). Two months following noise exposure, animals demonstrated marginally significant deficits in gap detection (p=.08) in comparison to controls. This decrease in gap detection resulted in decreased suppression of the acoustic startle response. TTS= temporary threshold shift induced by mild noise exposure

Tinnitus, oftentimes described as a perception of “ringing in the ears,” is the number one service related disability for Veterans (The Independent Budget, 2012). People employed in noisy environments, such as factory and construction workers, are also disproportionately affected by this condition (National Institute on Deafness and Other Communication Disorders). Our lab has previously demonstrated that noise and drug induced tinnitus result in deficits of GAP inhibition of the acoustic startle reflex (ASR), a behavioral measure of tinnitus, 48 hours following tinnitus generation (Holt, Bissig, Mirza, Rajah & Berkowitz, 2010). In addition, these same tinnitus models cause increased spontaneous neuronal activity (SNA) in the inferior colliculus (IC), a brain region that is key for the integration of auditory signals (Mulders & Robertson, 2013; Holt et al., 2010).

Noise exposed animals  (n=6) in comparison to the controls (n=6) show increased  MEMRI signal intensity (increased neuronal activity) 12 weeks after acoustic trauma in the central nucleus of the inferior colliculus.

Noise exposed animals (n=6) in comparison to the controls (n=6) show increased MEMRI signal intensity (increased neuronal activity) 12 weeks after acoustic trauma in the central nucleus of the inferior colliculus.

Hyperactivity in central auditory pathways may serve as the neural basis for the perception of tinnitus (Bauer, Turner, Caspary, Myers & Brozoski 2008; Brozoski, Bauer & Caspary, 2002; Kaltenbach, 2007; Kaltenbach & Afman, 2000). In the current study, we combine acoustic startle reflex (ASR) testing with manganese enhanced MRI (MEMRI) to test the hypothesis that deficits in GAP inhibition of the acoustic startle reflex and increased spontaneous neuronal activity will be present within 24 hours following noise exposure, and persist for three months. A hallmark of MEMRI is the use of manganese (Mn2+), an activity‐dependent contrast agent that enters active neurons through voltage‐gated calcium channels (Holt et al., 2010; Yu, Wadghiri, Sanes & Turnbull, 2005). Since regions of the brain with increased neuronal activity demonstrate increased Mn2+ uptake, MEMRI can be used to measure hyperactivity in central auditory structures following acoustic trauma.