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

 描述（由申请人提供）：该提案侧重于听觉感知的作用，这是研究领域标准（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。总体目标是描述听感觉学习的神经生物学和神经计算基础，以确定导致听觉知觉障碍（特别是听觉言语幻觉（AVH））的病理生理机制。我们的目标是招募以下人群：精神分裂症和情感性精神障碍伴轻度和重度AVH（分别为n=15和n=15）、妄想性精神障碍（不伴AVH的妄想性精神病; n=15）、耳鸣（不伴AVH的听觉感知障碍; n=15）和匹配的健康对照（不同程度的亚临床感知障碍; n=30）。我们将获得广泛的临床，神经认知和遗传特征，以及所有受试者的多模态成像：（1）使用[11 C]PHNO和安非他明范式，在丘脑，纹状体和中脑内D2/3受体和DA储存/释放能力的PET测量;（2）在概率听觉辨别任务期间听觉区域感觉预测错误信号的基于模型的fMRI测量; 3）听觉皮层中谷氨酸浓度的MR波谱测量;（4）感觉丘脑-皮层投射中基于任务和静息状态的fMRI连接测量;（5）基于血液DNA样品的全基因组测序。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（SA 1），并与纹状体和丘脑中的DA改变（SA 2）以及听觉皮层中的谷氨酸盐增加（SA 3）相关。我们还将探讨DA和谷氨酸（EA 1）之间的关系和听觉PE的听觉丘脑和听觉皮层（EA 2）之间的连接，并确定一组候选基因与听觉PE赤字（EA 3）在同一主题。 这RDoC建议将导致进一步理解的感觉学习的机制和他们的扰动条件与听觉感知改变。

 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.