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Pathophysiology of Auditory Hallucinations

幻听的病理生理学

基本信息

批准号：
8873997
负责人：
PHILIP CORLETT
金额：
$ 10.38万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2017-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8873997
关键词：
Accounting Anisotropy Anterior Auditory Hallucination Bilateral Brain Brain Part Brain region Coupling Data Detection Diagnosis Diffusion Magnetic Resonance Imaging Disease Distress Emotional Failure Financial compensation Frequencies Functional Magnetic Resonance Imaging Functional disorder Funding Generations Grant Hallucinations Homologous Gene Inferior Inferior frontal gyrus Intervention Judgment Left Leg Link Maps Measures Methods Modeling Pathway interactions Patients Persons Recording of previous events Relative (related person)Research Rest Schizoaffective Disorders Schizophrenia Site Social Functioning Source Speech Speech Perception Stimulus Structure of middle temporal gyrus Subgroup Sum Superior temporal gyrus Techniques Testing Time Transcranial magnetic stimulation Verbal Auditory Hallucinations Wernicke Area base blood oxygen level dependent experience insight neuroimaging phrases programs putamen repetitive transcranial magnetic stimulation response white matter

项目摘要

DESCRIPTION (provided by applicant): The overall objective of this R01 grant renewal is to ascertain the pathophysiological basis of auditory/verbal hallucinations (AVHs) in patients with schizophrenia and schizoaffective disorder. The proposed research plan derives from two fMRI studies completed during the initial grant period. The first detected heightened activity prior to AVHs in the left inferior frontal gyrus (IFG) and right temporal regions that in turn was preceded by elevated functional coupling between these regions. Our second study examined resting functional connectivity (FC) summed along a functional loop linking sites in Wernicke's area, a right homologue of Wernicke's area, left IFG, and the putamen. Hallucinators with schizophrenia demonstrated robustly greater FC summed across this corticostriatal loop compared to similarly diagnosed patients without AVHs and healthy controls. These findings suggest a specific hypothesis that will be further tested, namely that heightened corticostriatal coupling linking left IFG, posterior temporal regions and the putamen leads to episodic coactivation states that are hallucinogenic. Specific Aim #1 is to utilize two speech perception tasks to elicit excessive regional activation in hallucinators compared to nonhallucinating patients and healthy controls in the same brain regions comprising the corticostriatal loop found to be hyperconnected at baseline in this patient subgroup. One task is detection of negative emotionality expressed via speech intonation, while the second task is to distinguish meaningful phrases from phrases comprised partially of non-word syllable strings. Specific Aim #2 is to use fMRI during an inner speech generation task to test the hypothesis that corticostriatal hyperconnectivity detected in our completed study is a compensation arising from pathway inefficiency. Our prediction is that evidence of pathway inefficiency in hallucinating patients will not be detected, which is consistent with our alternative hyperconnectivity->coactivation model. Specific Aim #3 is to demonstrate aberrant white matter pathways that distinguish hallucinating patients from nonhallucinating patients and healthy controls. This will be accomplished by conducting a diffusion tensor imaging study to measure fractional anisotropy in the anterior arcuate fasciculus and mean diffusivity in the inferior longitudinal fasciculus. Specific Aim #4 is to demonstrate that at rest FC linking the putamen and Wernicke's area predicts subsequent improvement in AVHs following a course of bitemporal 1-Hz repetitive transcranial magnetic stimulation (rTMS), and that level of reduction in FC induced by this intervention also correlates positively with level of improvement in AVHs obtained. Twenty-five patients with schizophrenia spectrum disorder and active AVHs, 25 patients with similar diagnoses but without a recent history of AVHs, and 25 healthy controls will be studied. These studies will provide critical new insights into the mechanistic basis of AVHs.

描述（由申请人提供）：本次 R01 拨款更新的总体目标是确定精神分裂症和分裂情感障碍患者幻听/幻言 (AVH) 的病理生理学基础。拟议的研究计划源自于初始资助期间完成的两项功能磁共振成像研究。第一个检测结果是，在 AVH 之前，左额下回 (IFG) 和右颞区的活动增强，而这些区域之间的功能耦合又增强。我们的第二项研究检查了沿着韦尼克区（韦尼克区的右侧同源体）、左侧 IFG 和壳核的功能环连接位点总结的静息功能连接 (FC)。与没有 AVH 的类似诊断患者和健康对照相比，患有精神分裂症的幻觉者在皮质纹状体环上表现出明显更高的 FC 总和。这些发现提出了一个将被进一步检验的具体假设，即连接左 IFG、后颞区和壳核的皮质纹状体耦合增强会导致产生致幻作用的阵发性共激活状态。具体目标#1是利用两项言语感知任务来引发幻觉者与非幻觉患者和健康对照者相比，在相同的大脑区域中过度的区域激活，这些区域包括在该患者亚组中发现在基线处超连接的皮质纹状体环路。第一项任务是检测通过语音语调表达的负面情绪，而第二项任务是区分有意义的短语和部分由非单词音节串组成的短语。具体目标#2是在内部语音生成任务中使用功能磁共振成像来测试我们完成的研究中检测到的皮质纹状体超连接性是由于通路效率低下而产生的补偿这一假设。我们的预测是，不会检测到幻觉患者中通路效率低下的证据，这与我们的替代超连接->共激活模型一致。具体目标#3是证明异常的白质通路可以区分幻觉患者与非幻觉患者和健康对照。这将通过进行扩散张量成像研究来测量前弓状束的分数各向异性和下纵束的平均扩散率来实现。具体目标 #4 是证明，在休息时，连接壳核和韦尼克区的 FC 可以预测经过双颞叶 1 Hz 重复经颅磁刺激 (rTMS) 后 AVH 的后续改善，并且这种干预引起的 FC 减少水平也与获得的 AVH 改善水平呈正相关。将研究 25 名患有精神分裂症谱系障碍和活动性 AVH 的患者、25 名具有类似诊断但近期没有 AVH 病史的患者以及 25 名健康对照者。这些研究将为 AVH 的机制基础提供重要的新见解。