A Hearing Test for Hallucinations: Toward Development of Computational Markers for Early Diagnosis

幻觉听力测试：开发用于早期诊断的计算标记

• 批准号: 10456110
• 负责人: Albert R Powers
• 金额: $ 19.68万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-23 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456110
• 关键词: Address; Adopted; Auditory Hallucination; Behavioral; Belief; Biological Markers; Brain; Brain region; Cerebellum; Clinical; Clinical assessments; Cochlea; Complement; Computer Models; Data; Data Analyses; Deltastab; Detection; Development; Diagnosis; Diagnostic; Disease Marker; Early Diagnosis; Early identification; Early treatment; Environment; Evaluation; Exhibits; Exposure to; Frequencies; Functional Imaging; Functional disorder; Gaussian model; Goals; Hallucinations; Hearing; Hearing Tests; Hospitalization; Image; Individual; Insula of Reil; Knowledge; Laboratories; Learning; Link; Medical; Mentors; Modeling; Neurotransmitters; Organ; Outcome; Overweight; Participant; Patient Care; Patient Self-Report; Patients; Perception; Physiology; Predisposition; Process; Psychopathology; Psychoses; Psychotic Disorders; Publishing; Quality of life; Reporting; Research; Research Personnel; Retina; Risk; Schizophrenia; Science; Selection for Treatments; Sensory; Services; Severities; Structure of superior temporal sulcus; Suicide attempt; Symptoms; System; Testing; Therapeutic; Time; Training; Uncertainty; Visual; Voice; Weight; Work; auditory stimulus; base; care outcomes; career; clinical application; clinical high risk for psychosis; computational neuroscience; computerized tools; conditioning; experience; high risk; improved; improved outcome; information model; information processing; neuroimaging; psychosis risk; research clinical testing; sensory input; symposium; theories; visual stimulus

PROJECT SUMMARY / ABSTRACT Early identification of those at clinical high risk of psychosis (CHR) is critical for maximizing outcomes for those who convert. However, prediction relies largely on subjective symptom reports. Objective biomarkers are essential. My career goal is to use objective computational neuroscience to predict conversion in CHR. In work recently completed with my primary mentor (Dr. Corlett) and published in Science, I examined whether hallucinations might arise from an over-weighting of prior knowledge in perception. We used sensory conditioning to elicit hallucinatory experiences. Participants were exposed to repeated pairings of visual and auditory stimuli and subsequently perceived the auditory stimulus when only the visual was present. We applied this Conditioned Hallucinations paradigm to four groups: participants with psychosis both with (P+H+) and without (P+H-) hallucinations, healthy voice-hearers (P-H+), and healthy controls (P-H-). Conditioned hallucinations were markedly more frequent in those who hallucinate (P+H+ and P-H+) compared with those who do not (P+H-, P-H-). These behavioral data were used to estimate parameters of a Hierarchical Gaussian Filter (HGF) model with the laboratory of Dr. Stephan (co-mentor). Two different model parameters discriminated between groups of individuals with and without auditory hallucinations and, orthogonally, with and without a diagnosable psychotic disorder. On functional imaging analysis, activity in brain regions encoding low-level perceptual belief (e.g., insula, superior temporal sulcus) differentiated those with and without hallucinations. Activity in brain regions encoding change sensitivity (e.g., cerebellum) differentiated those with and without psychosis. These computational and imaging metrics may hasten the detection of conversion in CHR. However, more work is required. We propose 1) to determine whether these markers relate to risk of conversion in CHR; and 2) to determine whether they change with symptom severity over time. This research will provide training in the clinical application of computational models of perception, the evaluation of CHR, and longitudinal data analysis. Our work will be supported by formal didactics and symposia focused on the theory and practice of computational modeling. To meet my career goal, I must understand more deeply how to construct, alter, and utilize computational models of perception so that I may capture the subtle abnormalities of information processing that predate the development of frank hallucinations and psychosis. This proposal will provide me with the additional training and mentored research experiences necessary to become a fully independent investigator who brings the tools of computational neuroscience to the service of the early detection of psychosis.

项目总结/摘要 早期识别临床上精神病高危人群对于最大限度地提高治疗效果至关重要 对于那些皈依者。然而，预测在很大程度上依赖于主观症状报告。客观生物标志物 是必不可少的。我的职业目标是使用客观的计算神经科学来预测CHR的转换。 在最近与我的主要导师（Corlett博士）完成并发表在《科学》杂志上的工作中，我检查了 幻觉是否可能是由于感知中先验知识的过度权重而产生的。我们用感官 条件反射来引发幻觉参与者被暴露在重复配对的视觉和 听觉刺激和随后感知听觉刺激时，只有视觉存在。我们 将这种条件性幻觉范式应用于四组：患有精神病的参与者都有（P+H+） 无（P+H-）幻觉、健康听音者（P-H+）和健康对照（P-H-）。调节 幻觉（P+H+和P-H+）的发生率明显高于那些 而不是（P+H-，P-H-）。 这些行为数据被用来估计一个分层高斯滤波器（HGF）的参数 与Stephan博士（共同导师）的实验室合作。区分两种不同的模型参数 一组有和没有幻听的个体，正交地，有和没有可诊断的 精神障碍根据功能成像分析，大脑中编码低水平感知信念的区域的活动 (e.g.,颞上沟（上级颞沟）区分有和无幻觉。脑内活动 编码区域改变灵敏度（例如，小脑）区分那些有和没有精神病。这些 计算和成像指标可能会加速CHR转换的检测。然而，更多的工作是 必需的.我们建议：1）确定这些标志物是否与转换风险有关; 2） 确定它们是否随着症状严重程度的变化而变化。这项研究将提供培训， 知觉、知觉评估和纵向数据的计算模型的临床应用 分析.我们的工作将得到正式的教学法和专题讨论会的支持，重点是理论和实践， 计算建模 为了实现我的职业目标，我必须更深入地理解如何构建、改变和利用 感知的计算模型，这样我就可以捕捉到信息处理的微妙异常， 早于幻觉和精神病的发展这份提案将为我提供 成为完全独立的研究者所需的额外培训和指导研究经验 他将计算神经科学的工具用于精神病的早期检测。

项目成果

Paracingulate Sulcus Length Is Shorter in Voice-Hearers Regardless of Need for Care.

无论是否需要护理，发声者的副扣带沟长度都较短。

• DOI: 10.1093/schbul/sbaa067
• 发表时间: 2020
• 期刊: Schizophrenia bulletin
• 影响因子: 6.6
• 作者: Powers,AlbertR;vanDyck,LauraI;Garrison,JaneR;Corlett,PhilipR
• 通讯作者: Corlett,PhilipR

Navigating the Benefits and Pitfalls of Online Psychiatric Data Collection.

• DOI: 10.1001/jamapsychiatry.2021.2315
• 发表时间: 2021-11-01
• 期刊: JAMA PSYCHIATRY
• 影响因子: 25.8
• 作者: Quagan, Brittany;Woods, Scott W.;Powers, Albert R.
• 通讯作者: Powers, Albert R.

Psychotic Experiences in the General Population: Symptom Specificity and the Role of Distress and Dysfunction.

一般人群的精神病经历：症状特异性以及痛苦和功能障碍的作用。

• DOI: 10.1001/jamapsychiatry.2019.2391
• 发表时间: 2019
• 期刊: JAMA psychiatry
• 影响因子: 25.8
• 作者: Powers3rd,AlbertR

Development of Voluntary Control Over Voice-Hearing Experiences: Evidence From Treatment-Seeking and Non-Treatment-Seeking Voice-Hearers.

• DOI: 10.1093/schizbullopen/sgaa052
• 发表时间: 2020-01
• 期刊: Schizophrenia bulletin open
• 作者: Mourgues C;Negreira AM;Quagan B;Mercan NE;Niles H;Kafadar E;Bien C;Kamal F;Powers AR 3rd
• 通讯作者: Powers AR 3rd

Conditioned Hallucinations and Prior Overweighting Are State-Sensitive Markers of Hallucination Susceptibility.

• DOI: 10.1016/j.biopsych.2022.05.007
• 发表时间: 2022-11-15
• 期刊: Biological psychiatry
• 影响因子: 10.6