Neurobiological correlates of auditory processing in health and disease: an RDoC study

健康和疾病中听觉处理的神经生物学相关性：一项 RDoC 研究

• 批准号: 9080754
• 负责人: Anissa Abi-Dargham
• 金额: $ 73.25万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9080754
• 关键词: 22q11 Deletion Syndrome; Amphetamines; Auditory; Auditory Perception; Auditory area; Auditory system; Behavior; Blood; Blood specimen; Candidate Disease Gene; Categories; Clinical; Corpus striatum structure; DNA; DSM-IV; DSM-V; Delusional disorder; Delusions; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders; Disabled Persons; Disease; Distress; Dopamine; Dopamine Antagonists; Dopamine Receptor; Equipment and supply inventories; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Gene Expression Profile; Genes; Genetic; Globus Pallidus; Glutamates; Hallucinations; Health; Individual; Lead; Learning; Magnetic Resonance Spectroscopy; Measures; Midbrain structure; Modality; Modeling; Molecular; Morphology; Multimodal Imaging; Mutation; N-Methylaspartate; National Institute of Mental Health; Neurobiology; Neurocognitive; Pathway interactions; Patients; Perception; Perceptual disturbance; Phenotype; Play; Positron-Emission Tomography; Process; Psychotic Disorders; Recruitment Activity; Reporting; Research Domain Criteria; Rest; Risk Factors; Role; Sampling; Schizoaffective Disorders; Schizophrenia; Sensory; Sensory Process; Severities; Signal Transduction; Stimulus; Symptoms; Synaptic plasticity; Syndrome; System; Temporal Lobe; Testing; Thalamic structure; Tinnitus; Verbal Auditory Hallucinations; Water; Work; auditory discrimination; base; cognitive system; exome sequencing; genome sequencing; handicapping condition; hippocampal pyramidal neuron; human subject; improved; interdisciplinary approach; mouse model; neural correlate; neuroimaging; novel; peripheral blood; public health relevance; relating to nervous system; response; sensory mechanism; tool; transcriptome sequencing; transmission process; treatment strategy; whole genome

 DESCRIPTION (provided by applicant): This proposal focuses on the role of auditory perception, a subconstruct within the cognitive systems domain of the Research Domain Criteria (RDoC), in the pathophysiology of auditory perceptual disturbances in health and across traditional (DSM-IV and DSM-V) disease categories. The overall aim is to characterize the neurobiological and neurocomputational basis of auditory sensory learning to identify pathophysiological mechanisms leading to auditory perceptual disturbances and, specifically, auditory verbal hallucinations (AVH). We aim to recruit the following groups: schizophrenia and schizoaffective disorder with low- and high-severity AVH (n=15 and n=15, respectively), delusional disorder (delusional psychosis without AVH; n=15), tinnitus (auditory perceptual disturbances without AVH; n=15), and matched healthy controls (varying degrees of subclinical perceptual disturbances; n=30). We will obtain extensive clinical, neurocognitive, and genetic characterization, and multimodal imaging in all subjects: (1) PET measures of D2/3 receptors and DA storage/release capacity within the thalamus, striatum, and the midbrain, using [11C]PHNO and the amphetamine paradigm; (2) Model-based fMRI measures of sensory prediction-error signals in auditory regions during a probabilistic, auditory discrimination task; 3) MR spectroscopy measures of glutamate concentration in the auditory cortex; (4) Task-based and resting- state fMRI connectivity measures in sensory thalamo-cortical projections; (5) Whole genome sequencing based on blood DNA samples. We will test in the overall sample across diagnostic groups if auditory PE deficits predict AVH (SA1) and correlate with altered DA in striatum and thalamus (SA2) and with increased glutamate in the auditory cortex (SA3). We will also explore the relationship within the same subjects between DA and glutamate (EA1) and the relationships of auditory PE to connectivity between auditory thalamus and auditory cortex (EA2) and identify a set of candidate genes associated with auditory PE deficits (EA3). This RDoC proposal will lead to further understanding of the mechanisms of sensory learning and their perturbations in conditions associated with auditory perceptual alterations.