The brain is no longer viewed as a fixed system but a plastic system that adapts itself to optimally code for relevant stimuli. In some cases, the brain can experience abnormal plasticity. Hearing loss and tinnitus are two examples of debilitating conditions that affect millions of Americans and have been linked to abnormal tonotopic reorganization within the central auditory system. Understanding how tonotopic plasticity occurs within the auditory system and how we can acoustically and/or electrically stimulate the brain to induce appropriate changes in frequency coding to improve hearing can have significant clinical implications. Thus the long-term objective of the proposed studies is to map out the functional circuitry underlying tonotopic plasticity. Based on previous studies, plastic changes in frequency coding occur at all stages of the auditory pathway and involves both ascending and descending networks. However, the detailed functional organization between cortical and subcortical structures that can explain how tonotopic plasticity actually occurs within the central auditory system is still unknown. As an initial step towards identifying the detailed functional circuitry underlying tonotopic plasticity, the proposed studies will use various electrophysiological techniques to map out the functional and anatomical projection patterns from the primary auditory cortex (A1) to the central nucleus of the inferior colliculus (ICC). Both A1 and ICC have shown to play crucial roles in enabling central tonotopic reorganization. In particular, studies have demonstrated that best frequency (BF) shifts in A1 neurons induce similar BF shifts within subcortical structures, including ICC. Furthermore, BF shifts within ICC have also shown to contribute to BF shifts within A1. Using ketamine-anesthetized guinea pigs, the proposed studies will investigate how electrical stimulation of different frequency and isofrequency regions of A1 activate different frequency and isofrequency regions of ICC to begin to understand how A1 BF shifts induce similar shifts within ICC neurons. To identify the anatomical projection patterns, an innovative approach using antidromic stimulation will be used in which corticofugal neurons can be activated backwards from their axon terminals to their cell bodies. This method enables identification of mono- versus poly-synaptic projections from A1 throughout ICC. Thus in the same animal it is possible to map out the functional and anatomical projection pattern from A1 to ICC. Furthermore, BF shifts within ICC neurons will be induced using a conditioning paradigm (pure tone stimulation paired with stimulation of a BF matched A1 region). It is then possible to assess if and how the A1-to-ICC activation pattern altered as the acoustic-driven response patterns of ICC neurons change over time. These findings will begin to identify the functional circuitry underlying tonotopic plasticity that can guide future stimulation strategies for hearing loss and tinnitus. Furthermore, the developed electrophysiological methods can be expanded to investigate other brain regions of interest to the general neuroscience field.
In the U.S., approximately 36 million adults have reported hearing loss with about 40,000 receiving auditory implants and approximately 2 million people have reported debilitating tinnitus. Both tinnitus and poor speech perception with implants have been linked to abnormal frequency coding within the central auditory system. Thus the clinical goal of our proposed studies is to better understand how to acoustically and/or electrically activate the auditory system to improve frequency coding properties important for speech perception or tinnitus suppression.
|Lim, Hubert H; Lenarz, Thomas (2015) Auditory midbrain implant: research and development towards a second clinical trial. Hear Res 322:212-23|
|Markovitz, Craig D; Hogan, Patrick S; Wesen, Kyle A et al. (2015) Pairing broadband noise with cortical stimulation induces extensive suppression of ascending sensory activity. J Neural Eng 12:026006|
|Straka, M M; Hughes, R; Lee, P et al. (2015) Descending and tonotopic projection patterns from the auditory cortex to the inferior colliculus. Neuroscience 300:325-37|
|Markovitz, Craig D; Smith, Benjamin T; Gloeckner, Cory D et al. (2015) Investigating a new neuromodulation treatment for brain disorders using synchronized activation of multimodal pathways. Sci Rep 5:9462|
|Offutt, Sarah J; Ryan, Kellie J; Konop, Alexander E et al. (2014) Suppression and facilitation of auditory neurons through coordinated acoustic and midbrain stimulation: investigating a deep brain stimulator for tinnitus. J Neural Eng 11:066001|
|Straka, MaÅ‚gorzata M; McMahon, Melissa; Markovitz, Craig D et al. (2014) Effects of location and timing of co-activated neurons in the auditory midbrain on cortical activity: implications for a new central auditory prosthesis. J Neural Eng 11:046021|
|Straka, MaÅ‚gorzata M; Schmitz, Samuel; Lim, Hubert H (2014) Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway. J Neurophysiol 112:981-98|
|Markovitz, Craig D; Tang, Tien T; Lim, Hubert H (2013) Tonotopic and localized pathways from primary auditory cortex to the central nucleus of the inferior colliculus. Front Neural Circuits 7:77|
|Straka, Malgorzata M; Schendel, Dillon; Lim, Hubert H (2013) Neural integration and enhancement from the inferior colliculus up to different layers of auditory cortex. J Neurophysiol 110:1009-20|
|Johnson, Matthew D; Lim, Hubert H; Netoff, Theoden I et al. (2013) Neuromodulation for brain disorders: challenges and opportunities. IEEE Trans Biomed Eng 60:610-24|
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