Invasive and Noninvasive Brain Stimulation Strategies for the Treatment of Tinnitus

Abstract

The central auditory system consists of a series of relay stations at which auditory information is processed in stages before reaching the auditory cortex for sound perception. However, descending projections and non-auditory inputs into the central auditory system also play a vital role in shaping neural coding along the auditory pathway. The work in this thesis seeks to investigate the organization and role of these modulatory pathways of the central auditory system, particularly to devise and improve upon existing neuromodulation strategies for treating neurological disorders related to the auditory system, including tinnitus and hyperacusis. Through animal studies, we have shown that the descending projections from primary auditory cortex to subcortical centers, particularly the central nucleus of the inferior colliculus, exhibit a precise spatial organization based on frequency coding, supporting the role of the corticofugal system for modulating specific and relevant coding features within the ascending auditory system. Further, by combining stimulation of auditory cortex with an irrelevant acoustic stimulus, we were able to suppress neural firing throughout the inferior colliculus, revealing at least one potential mechanism for gating relevant versus irrelevant sound inputs. Targeting this gating mechanism could provide a neuromodulation treatment for tinnitus and/or hyperacusis which are associated with hyperactivity across auditory centers. Finally, we introduce a new neuromodulation approach using simultaneous noninvasive stimulation of multimodal pathways, focusing initially on somatosensory and auditory inputs. We present our proof-of-concept studies showing the ability to modulate neural coding in the inferior colliculus up to auditory cortex in a systematic way depending on the stimulation parameters (e.g., interstimulus interval and body stimulation location). These invasive and noninvasive techniques for modulating the brain provide potential options for the treatment of hearing disorders as well as other neurological and neuropsychiatric conditions.