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.

 描述（由申请人提供）：本提案重点关注听觉感知的作用，听觉感知是研究领域标准 (RDoC) 认知系统领域内的一个子结构，在健康和传统（DSM-IV 和 DSM-V）疾病类别中听觉感知障碍的病理生理学中的作用。总体目标是表征听觉感觉学习的神经生物学和神经计算基础，以确定导致听觉感知障碍，特别是幻听（AVH）的病理生理机制。我们的目标是招募以下群体：患有低严重度和高严重度 AVH 的精神分裂症和分裂情感性障碍（分别为 n=15 和 n=15）、妄想症（无 AVH 的妄想性精神病；n=15）、耳鸣（无 AVH 的听觉知觉障碍；n=15）以及匹配的健康对照（不同程度的亚临床知觉障碍；n=15）。 n=30）。我们将在所有受试者中获得广泛的临床、神经认知和遗传特征以及多模态成像：（1）使用 [11C]PHNO 和安非他明范例，对丘脑、纹状体和中脑内的 D2/3 受体和 DA 储存/释放能力进行 PET 测量； (2) 在概率性听觉辨别任务中，基于模型的功能磁共振成像测量听觉区域的感觉预测误差信号； 3) 磁共振波谱测量听觉皮层谷氨酸浓度； (4) 感觉丘脑皮质投射中基于任务和静息态的功能磁共振成像连接测量； (5)基于血液DNA样本的全基因组测序。我们将在诊断组的总体样本中测试听觉 PE 缺陷是否预测 AVH (SA1) 并与纹状体和丘脑 (SA2) 的 DA 改变以及听觉皮层 (SA3) 的谷氨酸增加相关。我们还将探讨同一受试者内 DA 和谷氨酸 (EA1) 之间的关系，以及听觉 PE 与听觉丘脑和听觉皮层 (EA2) 之间连接的关系，并确定一组与听觉 PE 缺陷相关的候选基因 (EA3)。 该 RDoC 提案将有助于进一步了解感觉学习的机制及其在与听觉感知改变相关的条件下的扰动。