Nikolas Francis - US grants

DESCRIPTION (provided by applicant): Interacting with natural acoustic environments requires learning how to respond to behaviorally meaningful sounds. The frontal cortex (FC) plays a central role in enabling us to learn associations between sounds and actions. Neurons within the FC are involved with attention, memory, knowledge of task rules, risk, and reward. A key feature of FC neurons is that they are highly adaptive in response to changes in ongoing cognitive demands. In this project, our long-term objective is to understand how the FC changes its neural codes for associations between sounds and their behavioral meanings when listening becomes difficult. Participating in a conversation in a crowded room is a common example of difficult listening, especially when neighboring voices are similar. It remains unclear how such listening tasks affect FC responses to sound for single neurons and small populations of neurons. To explore this topic, we developed an auditory task in which animals learn to receive a reward or avoid punishment by, respectively, continuing or stopping to lick a water spout in response to acoustic cues. We shall record neural responses in the FC while the animals perform these tasks. We hypothesize that increasing the similarity of task sounds will make the task more difficult, and that FC responses to the sounds will be modulated with similarity. Our preliminary results suggest that, even when the objective task-difficulty remains unchanged, the strength of FC responses is highly correlated with how well an animal performs the task. Thus, our results shed light on how the brain's response to sound changes according to the subjective experience of listening difficulty. In another twist on these questions, we shall consider how background noise makes listening difficult. Drawing from the previous example, having an intimate conversation in a crowded room will be difficult if the overall level of voices in the roo is high. To the best of our knowledge, the effect of background noise on FC responses to sounds during an auditory task has not been studied. To explore this topic, we will again have animals listen for behaviorally meaningful acoustic cues, but with the addition of acoustic background noise to increase task difficulty. We hypothesize that FC activity will be modulated by the level of noise, reflecting the animals' uncertainty in detecting the acoustic cues. Listenig can be challenging for healthy and hearing impaired people. Our studies will help clarify the basic understanding of FC physiology during difficult listening behaviors. As a result, our work will contribute to future therapies designed to enable better hearing in every-day settings.

Project Summary/Abstract Short-term memory (STM) is a fundamental component of hearing that is critical to speech comprehension and auditory communication. Mounting evidence has indicated that the activity in primary auditory cortex (A1) changes when we perform auditory tasks. In this project, our long-term objective is to understand how A1 changes its neural activity and connectivity during the maintenance of auditory STM. We will study how auditory STM is encoded in the structure of neural networks in A1 layer 2/3 (L2/3). We choose to study L2/3 because auditory STM involves an intracortical circuit, and L2/3 is dense in intracortical connectivity. To the best of our knowledge, the representation of STM in neural network structure has not been studied in A1. To explore this topic, we will have animals compare two sequential sounds that are separated by a silent delay. The animals must memorize the first sound to compare with the second sound to give a correct behavioral response during the task. We will record neuronal responses in A1 L2/3 while the animals perform this task. We hypothesize that the neural networks that arise during the first sound will be sustained during the delay until the second sound. We will use both simple and complex sounds to understand how acoustic complexity affects neuronal network structure. Furthermore, we will determine if there exists a stimulus-invariant representation of acoustic periodicity, i.e., `pitch', in neuronal networks. Our preliminary results suggest that neural activity in auditory cortex depends on if the animal successfully discriminates between high vs. low frequency pure-tones. Thus, our results shed light on how the brain's auditory responsiveness depends on how we listen and react to sound. Listening can be challenging for both healthy and hearing-impaired people. Our studies will help clarify the basic understanding of how the brain allows us to listen. As a result, our work will contribute to future therapies designed to enable better hearing in every-day settings.