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）：此R01授予更新的总体目标是确定精神分裂症和精神分裂症患者的听觉/言语幻觉（AVH）的病理生理基础。拟议的研究计划来自最初赠款期间完成的两项功能磁共振成像研究。在左下额回（IFG）和右颞区域中AVH之前的第一个检测到的活动又是在这些区域之间升高的功能耦合。我们的第二项研究检查了沿Wernicke地区的功能循环链接站点的静止功能连通性（FC），Wernicke地区的正确同源物，左IFG和Putamen。与没有AVH和健康对照的类似诊断的患者相比，具有精神分裂症的幻子剂表现出了在此皮质纹状体环上的强劲概述。这些发现提出了一个特定的假设，该假设将进一步检验，即链接左IFG的皮质纹状体偶联，后颞区和壳核导致具有幻觉剂的情节共激活状态。具体目的1是要利用两项语音感知任务来引起幻觉剂中的过度区域激活，与非抗溶解的患者和在该患者子组中基线相关的同一大脑区域的非耐盐酸对照和健康对照相比。一项任务是检测通过语音语调表达的负面情绪，而第二个任务是将有意义的短语与部分由非单词音节字符串组成的短语区分开来。具体目的＃2是在内部语音生成任务中使用fMRI来检验以下假设：在我们完成的研究中检测到的皮质纹状体超连续性是由途径效率低下引起的补偿。我们的预测是，将无法检测到幻觉患者效率低下的证据，这与我们的替代性超连续性 - >共激活模型一致。特定目的＃3是展示异常的白质途径，这些途径将幻觉与非降解患者和健康对照组区分开。这将通过进行扩散张量成像研究来实现，以测量前弓形前孔中的分数各向异性和下纵向筋膜中的平均扩散率。具体目的4是要证明，在将ptamen和Wernicke的区域连接起来的休息FC时，预测随后在BITEMAL 1-Hz重复的经颅磁刺激（RTMS）的过程后，AVH的改善，而通过这种干预诱导的FC的水平也与AVHS获得的改善水平相关。 25例精神分裂症谱系障碍和活性AVH患者，25例具有相似诊断的患者，但没有最近的AVH病史，将研究25例健康对照。这些研究将为AVH的机械基础提供关键的新见解。