Degree Name
PhD (Doctor of Philosophy)
Program
Biomedical Sciences
Date of Award
8-2025
Committee Chair or Co-Chairs
Dr. Siva Digavalli
Committee Members
Brooks Pond, Justin Gass, Russell Brown, Sethu Sankaranarayanan
Abstract
Auditory processing begins in the cochlea and ascends through brainstem relays to the cortex, where sound features with increasing complexity are encoded. The 40 Hz auditory steady-state response (ASSR) reflects induced gamma synchrony shaped by local cortical circuit dynamics. Disrupted 40 Hz ASSR is a consistent finding in schizophrenia, linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction in inhibitory interneurons, making it a promising translational biomarker. While multiple ASSR generators have been identified, it is not known if these are redundant or represent unique activity. This dissertation investigates regional differences in 40 Hz ASSR across two principal generators: the primary auditory cortex (Actx) and prefrontal cortex (PFC) in awake Sprague-Dawley rats using epidural EEG. We hypothesized that specific regions encode click trains differently; that is, earlier stations of the auditory neuraxis (e.g. Actx) are more sensitive to basic stimulus features, while later stations (e.g. PFC) support more abstract information processing. Given that regional encoding may reflect distinct circuit configurations, including varying receptor densities and subtypes, we varied stimulus parameters (intensity, click number, jitter) and assessed ASSR responses before and after pharmacological manipulation (e.g., NMDAR antagonists, atypical antipsychotics). The Actx exhibited rapid (~ 40 ms onset), phase-locked gamma synchrony that was robust across some stimulus feature manipulations. In contrast, the PFC displayed delayed (~200 ms), phase-locked gamma that emerged only with some types of stimuli (e.g. click trains but not triangle waves) that carried a threshold number (≥8) of stimuli requirement and was disrupted by even minor timing variability (±4% of the interclick interval). Higher harmonics of ASSR were reliably observed but differentially affected by pharmacological treatment, suggesting that complex sounds like click trains are encoded through multiple frequency channels. Low doses of the NMDA receptor antagonist, MK801, augmented gamma synchrony in the Actx but abolished the same in the PFC. Conversely, clozapine and risperidone enhanced gamma synchrony in the PFC while disrupting it in the Actx, highlighting region-specific effects. Overall, these findings establish that 40 Hz ASSR can encode distinctly across cortical regions and could serve as a regional, pharmacologically sensitive, translational biomarker for guiding drug development in neuropsychiatry.
Document Type
Dissertation - embargo
Recommended Citation
Gautam, Deepshila, "Hierarchy In Sensation: Exploring the 40 Hz Auditory Steady State Synchrony in The Primary Auditory and Prefrontal Association Cortices" (2025). Electronic Theses and Dissertations. Paper 4589. https://dc.etsu.edu/etd/4589
Copyright
Copyright by the authors.
Included in
Other Neuroscience and Neurobiology Commons, Pharmacology Commons, Systems Neuroscience Commons
