There have been many recent developments in invasive and non-invasive techniques for modulating brain operations. However, these techniques typically cannot be efficiently used beyond ?proof of concept? experiments since the cellular-network origins of the most basic functions in the brain are not known. Part of the reason for this is that while cognitive neuroscientists have learned a lot about the principles that govern brain operations, and computational modelers have made leaps and bounds in creating models of nearly every brain circuit, these two fields remain only sparsely connected. Our proposed project will bridge the gap between cognitive neuroscience, electrophysiology, and computational modeling by measuring neuronal activity on multiple spatial scales in behavioral experiments, and connecting these data to detailed computational models of the auditory thalamocortical system. This process will provide specific predictions for the neuromodulation of auditory system function and form a solid base for novel therapeutic approaches. Our project focuses on defining the cellular-network underpinnings of three distinct mechanisms of auditory perceptual processes, which are utilized for speech processing. The first is the flexibility of neuronal oscillations in the delta-theta bands that endows them with the capability to dynamically adapt their cycles to the quasi-rhythmic structure of naturalistic auditory stimulus sequences, including species specific vocalizations and speech. The second mechanism that supports efficient auditory processing is oscillatory phase reset, which enables the precise tracking of stimulus sequences by neuronal oscillations supporting, amongst other things the figure-ground segregation of attended auditory streams. The third fundamental mechanism for processing continuous auditory stimulus streams is parsing, which enables the brain to segment and group acoustic elements so that they form units that are interpretable by the brain. These three mechanisms form the basis of the complex computations needed to make sense of the auditory environment. We will perform concurrent thalamus-cortex electrophysiological recordings in macaques to determine the spatiotemporal organization of neuronal activity patterns supporting the above described fundamental auditory processing mechanisms. The data collected during behavioral tasks will inform our detailed thalamocortical computational model, which will in turn provide precise predictions on efficient neuromodulation approaches to induce, or temporarily inhibit the neuronal activity patterns underlying distinct auditory processes like stream segregation or parsing. Besides advanced time-resolved single unit and neuronal ensemble activity analyses, we will be able to verify the effectiveness of neuromodulation based on behavioral biases. The model based, targeted neuromodulation techniques developed by our proposed projects will pave the way for novel therapeutic approaches in the treatment of neuropsychiatric and developmental disorders that are hallmarked by deficits in the dynamical properties of neuronal oscillatory systems.

Public Health Relevance

Using data obtained with electrophysiological recordings spanning multiple spatial scales, coupled with advanced data analyses, we are developing a detailed model of the brain?s auditory thalamocortical circuits and their hallmark neuronal oscillatory patterns, which support distinct functions, like auditory selective attention and speech segmentation. We will use the model and experimental data to better understand the brain and the characteristic neuronal deficits underlying a variety of brain diseases, including schizophrenia and autism spectrum disorders. This improved understanding will lead to the development of novel, precisely targeted neuromodulation methods that will first be tested within the model and then could be used to restore intricate neuronal oscillatory dynamics altered in numerous neuropsychiatric and developmental disorders.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
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Poremba, Amy
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Nathan Kline Institute for Psychiatric Research
United States
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Barczak, Annamaria; O'Connell, Monica Noelle; McGinnis, Tammy et al. (2018) Top-down, contextual entrainment of neuronal oscillations in the auditory thalamocortical circuit. Proc Natl Acad Sci U S A 115:E7605-E7614
Zoefel, Benedikt; Costa-Faidella, Jordi; Lakatos, Peter et al. (2017) Characterization of neural entrainment to speech with and without slow spectral energy fluctuations in laminar recordings in monkey A1. Neuroimage 150:344-357
Obleser, Jonas; Henry, Molly J; Lakatos, Peter (2017) What do we talk about when we talk about rhythm? PLoS Biol 15:e2002794
Lakatos, Peter; O'Connell, Monica N; Barczak, Annamaria (2016) Pondering the Pulvinar. Neuron 89:5-7
Lakatos, Peter; Barczak, Annamaria; Neymotin, Samuel A et al. (2016) Global dynamics of selective attention and its lapses in primary auditory cortex. Nat Neurosci 19:1707-1717
Neymotin, S A; McDougal, R A; Bulanova, A S et al. (2016) Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex. Neuroscience 316:344-66
Neymotin, Samuel A; Dura-Bernal, Salvador; Lakatos, Peter et al. (2016) Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex. Front Pharmacol 7:157
Haegens, Saskia; Barczak, Annamaria; Musacchia, Gabriella et al. (2015) Laminar Profile and Physiology of the ? Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex. J Neurosci 35:14341-52
Martínez, Antígona; Gaspar, Pablo A; Hillyard, Steven A et al. (2015) Neural oscillatory deficits in schizophrenia predict behavioral and neurocognitive impairments. Front Hum Neurosci 9:371
O'Connell, M N; Barczak, A; Ross, D et al. (2015) Multi-Scale Entrainment of Coupled Neuronal Oscillations in Primary Auditory Cortex. Front Hum Neurosci 9:655

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