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

基本信息

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
项目类别：
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

项目摘要

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.

描述（由适用提供）：该提案着重于听觉感知的作用，这是研究领域标准的认知系统领域（RDOC）在健康和传统（DSM-IV和DSM-V）疾病中的听觉感知障碍的病理生理学中。总体目的是表征听觉感觉学习的神经生物学和神经计算基础，以鉴定导致听觉感知障碍的病理生理机制，尤其是听觉口语幻觉（AVH）。我们旨在招募以下组：具有低度和高度AVH（分别为n = 15和n = 15）的精神分裂症和精神分裂症（分别为n = 15和n = 15），妄想障碍（没有AVH的妄想精神；亚临床感知疾病的程度； n = 30）。我们将在所有受试者中获得广泛的临床，神经认知和遗传表征以及多模式成像：（1）使用[11C] Phno和Amphetamine paradigm在丘脑，纹状体和中脑内的D2/3受体和DA存储/释放能力的PET测量；（2）基于模型的fMRI测量在概率，听觉歧视任务期间，听觉区域中的感觉预测信号； 3）听觉皮层中谷氨酸浓度的MR光谱测量；（4）在感觉thalammo-cortical投影中基于任务和静止状态fMRI连接度量；（5）基于血液DNA样品的整个基因组测序。如果听觉PE定义了预测AVH（SA1），并且与纹状体和丘脑（SA2）（SA2）（SA2）中的DA相关，并且与听觉皮层（SA3）中的谷氨酸增加，我们将在诊断组的总体样本中进行测试。我们还将探讨DA和谷氨酸（EA1）之间相同主题的关系，以及听觉PE与听觉丘脑与听觉皮层（EA2）之间的连通性的关系，并识别一组与听觉PE相关的候选基因（EA3）。该RDOC建议将进一步了解与听觉感知改变有关的感觉学习机制及其在扰动中的机制。