NCS-FO: SOUND: Understanding the Functional Neural Dynamics Underpinning Auditory Processing Dysfunctions through a Multiscale Recording-Stimulation Framework

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Auditory processing dysfunction (APD) is a common feature of many types of psychosis, including schizophrenia, and is associated with multiple core symptoms, including auditory verbal hallucinations (i.e. hearing voices). Despite APD’s high prevalence, affecting up to 80% of the psychotic population, pharmaceutical therapy is ineffective: 70% of patients either have undesirable side effects or experience persistent symptoms despite treatment. A non-pharmacological treatment strategy, such as neuromodulation (targeted stimulation of nerves), would meet an important medical need. Although neuromodulation has recently emerged as a plausible therapeutic tool for a range of neuropsychological conditions, little is understood of the abnormal neural patterns underlying APD. This project will utilize an innovative framework, integrating multiscale recording and stimulation, to explore APD and to elucidate its underlying mechanisms. The project unites a multidisciplinary team of researchers, including experts in neural signal processing, neuroscience, psychiatry, and deep learning. The proposed work will develop computational, data-driven approaches in real-world settings. These will investigate multimodal signals with distinct spatiotemporal properties, integrated with a neuroimaging study of psychosis with APD. In addition to the scientific impacts of this proposal, the proposed work will advance national health by addressing multiple existing gaps in neuroscience and psychiatry. The educational and outreach plans will provide training opportunities for women and under-represented minoroties, promoting STEM diversity in the Northeastern United States.This project has three main thrusts. All of the proposed frameworks are data-driven and will be tested on healthy controls and patients with schizophrenia, in whom APD is a core feature. The first thrust will develop a computational statistical approach to quantify hierarchical couplings between hemodynamic infra-slow oscillations (using fNIRS), and electrical high-frequency oscillations (using EEG), through a nested multimodal approach in auditory task-related settings. The second thrust introduces an innovative multimodal data fusion approach to exploit complementary strengths from electrical and vascular dynamics, toward an integrative understanding of APD. This will enable identification of across-subject and within-subject signals underlying APD. The third thrust will extent beyond functional investigations and into causal dynamics across large-scale networks. The research will develop fused causal models, to identify subject-specific causal patterns of APD, and to create individualized spatial target mapping for optimal site stimulation. The precise locations of aberrant causal patterns will be targets for transcranial direct-current stimulation (tDCS). Project outcomes include the introduction of an innovative computational data fusion approach to bridge distinct spatiotemporal scales; discovery of latent signatures and causal patterns of APD through novel neural information processing; insight into APD hierarchical mechanisms, and understanding of the cortical modulatory properties of APD.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.