Elucidating neural circuits and pupil readouts of motivated effortful listening

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Project Summary . Attending to a speaker in a noisy environment, such as a cocktail party, can be an effortless and pleasantly immersive experience for individuals with normal hearing and cognitive function. However, for individuals with hearing loss, this ‘listening effort’ is their primary complaint, and can be a severe source of stress and fatigue that impacts their quality of life and employment. Unlike an audiogram, which can be measured objectively, listening effort is a high-level cognitive process, and challenging to measure. Pupillometry, measuring the size of the pupil of the eye, has proven extremely useful as a physiological readout of listening effort. However, we have very little understanding about the neural interactions underlie mental effort, and therefore do not know what the pupil tells us, specifically, about these circuits. Experiments are needed that behaviorally engage listening effort while probing the underlying neural circuits mechanisms, and determining which circuit interactions are read out by pupil dilation. Our laboratory has recently developed a behavioral approach to study the attentional component of listening effort (attentional effort), in mice. Mice report detection of temporal coherence in ongoing noise by licking for sugar reward. We parametrically vary the difficulty on each trial, and manipulate listening effort by changing reward volume in blocks of trials. We find that mice expend more attentional effort during high-reward blocks, resulting in better detection of temporal coherence during blocks. In parallel work, we have extensively characterized the physiological correlates in the auditory system of several pupillometry metrics during a simpler auditory detection behavior. Furthermore, human and animal work consistently show that frontal cortex structures that combine task performance and motivational information are active during attentional effort. These results lead to the following central hypothesis: differences in cortical coding between states of low and high reward, result from changes in modulation on fast and slow time scales, together with auditory-frontal interactions that enhance coding of high-value sounds and provide feedback signals that improve subsequent performance, and that these circuits are upregulated after hearing loss. We will test this hypothesis by electrically recording from neurons in the auditory cortex and assaying their coding of sounds, while two-photon imaging or optopgenetically manipulating inputs from neuromodulatory systems or frontal cortex, and doing pupillometry during our listening effort task. Our results will reveal the contributions of neuromodulatory and frontal cortex inputs to auditory cortex to shifts in listening effort allocated to temporal coherence detection, and will directly relate multiple pupil metrics and statistical modeling approaches to these circuit mechanisms.