Distributed cortical feedback mechanisms for context-dependent auditory processing

The National Institute on Deafness and Other Communication Disorders awarded Carnegie Mellon University $100,228 on January 16, 2027, under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) to develop and apply a high-density cortical inactivation platform for studying distributed cortical feedback mechanisms in auditory processing.

The research investigates how multiple higher-order cortical regions exert top-down feedback onto primary auditory cortex to modulate context-dependent auditory perception. The work develops a novel platform enabling rapid, trial-wise silencing of nine distinct higher-order cortical regions within a single recording session, paired with extracellular electrophysiology and population-level neural analyses. Aim 1 establishes how each feedback source modulates frequency tuning and reorganizes auditory-cortical population activity during passive listening in mice. Aim 2 determines how behavioral engagement reconfigures these distributed networks and how higher-order regions contribute to active transformation of auditory cortex responses when task demands change; mice perform a short-term working-memory auditory categorization task while individual feedback pathways are transiently inactivated during defined behavioral epochs. By comparing the same neural populations across passive listening and active task performance, the research quantifies how feedback pathways shape context-dependent reorganization of sensory representations.

The award is a Project Grant assistance type with performance at Carnegie Mellon's Office of Sponsored Programs in Pittsburgh, Pennsylvania. The period of performance runs from January 16, 2027, through August 31, 2029.

Abstract

Adaptive auditory perception depends on the brain's ability to flexibly transform acoustic input into representations that support accurate behavior. Higher-order cortical regions play a critical role in this process by exerting top-down feedback onto primary sensory areas, yet most studies examine these pathways individually, leaving unresolved how multiple feedback sources jointly modulate auditory cortex (actx). As a result, we lack a systems-level understanding of how distributed corticocortical inputs collectively shape sensory representations and how their influence changes when sounds gain behavioral relevance. This proposal develops and applies a novel, high-density cortical inactivation platform that allows rapid, trial- wise silencing of nine distinct higher-order cortical regions within a single recording session. By pairing this approach with extracellular electrophysiology and rigorous population-level analyses, aim 1 will establish how each feedback source modulates frequency tuning and reorganizes auditory-cortical population activity during passive listening. These experiments will provide the first direct comparison of multiple corticocortical pathways acting on actx at the single-neuron level under matched conditions, generating an integrated characterization of distributed cortical feedback in sensory cortex. Aim 2 will determine how behavioral engagement reconfigures these distributed networks and how higher- order regions contribute to the active transformation of actx responses when task demands change. Mice will perform a short-term working-memory auditory categorization task while individual feedback pathways are transiently inactivated during defined behavioral epochs. By comparing the same neural populations across passive listening and active task performance, we will quantify how these feedback pathways shape context- dependent reorganization and the modulation of sensory encoding during stimulus evaluation, memory maintenance, and choice execution. This aim will identify which higher-order regions drive the state-dependent shift from passive sensory processing to active, behaviorally relevant computation in actx. Together, the proposed work will deliver a comprehensive framework for how higher-order cortical regions jointly sculpt auditory-cortical processing across passive and active states. By integrating large-scale perturbations with single-unit and population analyses, this research will establish an organizing principle for distributed cortical feedback, advancing our understanding of how sensory cortex is shaped by the broader cortical network.