EFFECTS OF AGING ON MIDBRAIN AND CORTICAL SPEECH-IN-NOISE PROCESSING

Older adults frequently report that they can hear what they have been told but cannot understand the meaning. This is particularly true in noisy conditions, where the additional challenge of suppressing irrelevant noise (i.e. a competing talker) adds another layer of difficulty to their speech understanding. Hearing aids improve speech perception in quiet, but their success in noisy environments has been modest, suggesting that peripheral hearing loss may not be the only factor in the older adult’s perceptual difficulties. Recent animal studies have shown that auditory synapses and cells undergo significant age-related changes that could impact the integrity of temporal processing in the central auditory system. Psychoacoustic studies carried out in humans have also shown that hearing loss can explain the decline in older adults’ performance in quiet compared to younger adults, but these psychoacoustic measurements are not accurate in describing auditory deficits in noisy conditions. These results would suggest that temporal auditory processing deficits could play an important role in explaining the reduced ability of older adults to process speech in noisy environments. The goals of this dissertation were to understand how age affects neural auditory mechanisms and at which level in the auditory system these changes are particularly relevant for explaining speech-in-noise problems. Specifically, we used non-invasive neuroimaging techniques to tap into the midbrain and the cortex in order to analyze how auditory stimuli are processed in younger (our standard) and older adults. We will also attempt to investigate a possible interaction between processing carried out in the midbrain and cortex.

A Search for Muon Neutrinos in Coincidence with Gamma-Ray Bursts in the Southern Hemisphere Sky Using the IceCube Neutrino Observatory

The origin of observed ultra-high energy cosmic rays (UHECRs, energies in excess of $10^{18.5}$ eV) remains unknown, as extragalactic magnetic fields deflect these charged particles from their true origin. Interactions of these UHECRs at their source would invariably produce high energy neutrinos. As these neutrinos are chargeless and nearly massless, their propagation through the universe is unimpeded and their detection can be correlated with the origin of UHECRs. Gamma-ray bursts (GRBs) are one of the few possible origins for UHECRs, observed as short, immensely bright outbursts of gamma-rays at cosmological distances. The energy density of GRBs in the universe is capable of explaining the measured UHECR flux, making them promising UHECR sources. Interactions between UHECRs and the prompt gamma-ray emission of a GRB would produce neutrinos that would be detected in coincidence with the GRB’s gamma-ray emission. The IceCube Neutrino Observatory can be used to search for these neutrinos in coincidence with GRBs, detecting neutrinos through the Cherenkov radiation emitted by secondary charged particles produced in neutrino interactions in the South Pole glacial ice. Restricting these searches to be in coincidence with GRB gamma-ray emis- sion, analyses can be performed with very little atmospheric background. Previous searches have focused on detecting muon tracks from muon neutrino interactions fromthe Northern Hemisphere, where the Earth shields IceCube’s primary background of atmospheric muons, or spherical cascade events from neutrinos of all flavors from the entire sky, with no compelling neutrino signal found. Neutrino searches from GRBs with IceCube have been extended to a search for muon tracks in the Southern Hemisphere in coincidence with 664 GRBs over five years of IceCube data in this dissertation. Though this region of the sky contains IceCube’s primary background of atmospheric muons, it is also where IceCube is most sensitive to neutrinos at the very highest energies as Earth absorption in the Northern Hemisphere becomes relevant. As previous neutrino searches have strongly constrained neutrino production in GRBs, a new per-GRB analysis is introduced for the first time to discover neutrinos in coincidence with possibly rare neutrino-bright GRBs. A stacked analysis is also performed to discover a weak neutrino signal distributed over many GRBs. Results of this search are found to be consistent with atmospheric muon backgrounds. Combining this result with previously published searches for muon neutrino tracks in the Northern Hemisphere, cascade event searches over the entire sky, and an extension of the Northern Hemisphere track search in three additional years of IceCube data that is consistent with atmospheric backgrounds, the most stringent limits yet can be placed on prompt neutrino production in GRBs, which increasingly disfavor GRBs as primary sources of UHECRs in current GRB models.

Physiological Effects of Alcohol on Crayfish Escape Circuitry

Alcohol is one of the oldest and most widely used drugs on the planet, but the cellular mechanisms by which it affects neural function are still poorly understood. Unlike other drugs of abuse, alcohol has no specific receptor in the nervous system, but is believed to operate through GABAergic and serotonergic neurotransmitter systems. Invertebrate models offer circuits of reduced numerical complexity and involve the same cell types and neurotransmitter systems as vertebrate circuits. The well-understood neural circuits controlling crayfish escape behavior offer neurons that are modulated by GABAergic inhibition, thus making tail-flip circuitry an effective circuit model to study the cellular mechanisms of acute alcohol exposure. Crayfish are capable of two stereotyped, reflexive escape behaviors known as tail-flips that are controlled by two different pairs of giant interneurons, the lateral giants (LG) and the medial giants (MG). The LG circuit has been an established model in the neuroscience field for more than 60 years and is almost completely mapped out. In contrast, the MG is still poorly understood, but has important behavioral implications in social behavior and value-based decision making. In this dissertation, I show that both crayfish tail-flip circuitry are physiologically sensitive to relevant alcohol concentrations and that this sensitivity is observable on the single cell level. I also show that this ethyl alcohol (EtOH) sensitivity in the LG can be changed by altering the crayfish’s recent social experience and by removing descending inputs to the LG. While the MG exhibits similar physiological sensitivity, its inhibitory properties have never been studied before this research. Through the use of electrophysiological and pharmacological techniques, I show that the MG exhibits many similar inhibitory properties as the LG that appear to be the result of GABA-mediated chloride currents. Finally, I present evidence that the EtOH-induced changes in the MG are blocked through pre-treatment of the potent GABAA receptor agonist, muscimol, which underlines the role of GABA in EtOH’s effects on crayfish tail-flip circuitry. The work presented here opens the way for crayfish tail-flip circuitry to be used as an effective model for EtOH’s acute effects on aggression and value-based decision making.