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Mechanisms of impaired subcortical auditory processing in schizophrenia

精神分裂症皮层下听觉处理受损的机制

基本信息

批准号：
10247065
负责人：
John Connor Williams
金额：
$ 5.1万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2023-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10247065
关键词：
22q11.2 Antipsychotic Agents Assessment tool Attenuated Auditory Auditory Perception Auditory area Base of the Brain Bayesian Analysis Brain Chicago Chronic Clinical Clinical Medicine Code Conscious Corpus striatum structure Data Development DiGeorge Syndrome Diagnosis Disease Dopamine Dopamine D2 Receptor Dose Economic Burden Environment Ethics Etiology Failure Functional Magnetic Resonance Imaging Funding Generations Geniculate body structure Goals Hallucinations Haloperidol Homelessness Human Impairment Imprisonment Individual Lead Learning Life Expectancy Linear Models Link Location Magnetic Resonance Imaging Measures Medial Mediating Mediation Medical Methods Modeling Mus Neurobiology Overweight Pathogenesis Patients Perception Perceptual disturbance Physicians Play Process Psychoses Psychotic Disorders Rattus Reporting Research Research Personnel Research Proposals Research Training Resources Rest Risk Role Schizoaffective Disorders Schizophrenia Scientist Sensory Severities Signal Transduction Speech Discrimination Stimulus Symptoms Synapses Syndrome Testing Thalamic Nuclei Thalamic structure Training Training Programs Translational Research Unemployment United States United States National Institutes of Health Verbal Auditory Hallucinations Weight auditory discrimination auditory processing base clinical imaging clinical predictors cognitive neuroscience disability disorder risk expectation experience genetic risk factor imaging study improved microdeletion mouse model novel novel strategies relating to nervous system sensory input social transmission process

项目摘要

Project Summary Schizophrenia is among the most severe and burdensome medical conditions worldwide, yet the pathophysiological basis for symptoms experienced by patients remain unknown. This F30 application presents a research and training program that will support the applicant on a path towards becoming an NIH- funded independent investigator and physician-scientist focused on understanding the neurobiology of schizophrenia and related psychotic disorders. The activities in this application build on the candidate’s prior training and are set in a resource-rich environment that will facilitate the development of expertise in: 1) principles of clinical imaging in schizophrenia, 2) methods in cognitive neuroscience and functional magnetic resonance imaging (fMRI), 3) model-based analysis of auditory processing using fMRI, 4), fundamentals of clinical medicine and translational research, and 5) the responsible and ethical conduct of research. This research proposal aims to determine the relationships between auditory verbal hallucinations (AVH) experienced by individuals with schizophrenia and previous findings of: 1) impaired thalamocortical connectivity in mouse models of 22q11 deletion syndrome (22q11DS), the strongest known genetic risk factor for psychosis; 2) reduced resting-state functional connectivity between MGN and AC in patients with schizophrenia; and 3) impaired computational processes in auditory cortex and MGN. The overarching goal of the research to be carried out in this application is to use resting-state, task-based, and model-based multiband fMRI to identify impairments that correlate with the presence and severity of AVH in: 1) connectivity between medical geniculate nucleus (MGN) and auditory cortex (AC), and 2) auditory learning and percept generation in medial geniculate nucleus. I aim to study the following groups of individuals: unmedicated patients with SCZ and schizoaffective disorder (n=30) and matched healthy controls (varying degrees of subclinical perceptual disturbances; n=30). Using a thalamic localizer fMRI task, voxels comprising the medial geniculate nucleus will be identified in each subject. Subsequently, resting-state functional connectivity (RSFC) between MGN and AC will be determined using task-free fMRI. Using a model-based auditory discrimination fMRI task, neurocomputational underpinnings of auditory learning and percept generation will be measured. Neurobiological impairments detected via fMRI will be correlated with clinical measures of AVH severity. Such evidence would have important implications for our understanding of the brain bases of auditory verbal hallucinations and the pathogenesis of schizophrenia and would help generate new targets for treatment of this devastating illness.

项目总结