Auditory speech and cognitive networks in hallucinators across the psychosis spectrum

整个精神病谱系中幻觉者的听觉言语和认知网络

基本信息

批准号：
8700834
负责人：
ANN Kyungah SHINN
金额：
$ 18.14万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8700834
关键词：
Address Adverse effects Anisotropy Anterior Antipsychotic Agents Area Attention Attenuated Auditory Auditory Hallucination Auditory Perception Auditory area Bipolar Disorder Brain Brain region Categories Clinical Cognitive Conflict (Psychology)DSM-IV Data Diagnosis Diagnostic Dimensions Disease Distress Dorsal Eye Female Fiber Frequencies Functional Magnetic Resonance Imaging Functional disorder Hearing Heterogeneity Individual Intervention Knowledge Language Left Literature Matched Group Medicine Modeling Monitor Neurobiology Neurosciences Pathogenesis Patients Perception Pharmaceutical Preparations Play Process Production Psychiatrist Psychotic Disorders Recording of previous events Refractory Research Residencies Resources Rest Schizoaffective Disorders Schizophrenia Seeds Severities Severity of illness Specific qualifier value Speech Staging Stimulus Symptoms Temporal Lobe Training Transcend Verbal Auditory Hallucinations Voice auditory stimulus base biological research career development cingulate cortex cognitive control cognitive neuroscience cohort effective intervention falls functional group grasp insight interest language processing male neurofeedback neuroimaging public health relevance repetitive transcranial magnetic stimulation suicidal risk

Address Adverse effects Anisotropy Anterior Antipsychotic Agents Area Attention Attenuated Auditory Auditory Hallucination Auditory Perception Auditory area Bipolar Disorder Brain Brain region Categories Clinical Cognitive Conflict (Psychology)DSM-IV Data Diagnosis Diagnostic Dimensions Disease Distress Dorsal Eye Female Fiber Frequencies Functional Magnetic Resonance Imaging Functional disorder Hearing Heterogeneity Individual Intervention Knowledge Language Left Literature Matched Group Medicine Modeling Monitor Neurobiology Neurosciences Pathogenesis Patients Perception Pharmaceutical Preparations Play Process Production Psychiatrist Psychotic Disorders Recording of previous events Refractory Research Residencies Resources Rest Schizoaffective Disorders Schizophrenia Seeds Severities Severity of illness Specific qualifier value Speech Staging Stimulus Symptoms Temporal Lobe Training Transcend Verbal Auditory Hallucinations Voice auditory stimulus base biological research career development cingulate cortex cognitive control cognitive neuroscience cohort effective intervention falls functional group grasp insight interest language processing male neurofeedback neuroimaging public health relevance repetitive transcranial magnetic stimulation suicidal risk

展开

项目摘要

DESCRIPTION (provided by applicant): This K23 proposal aims to understand auditory, speech, and cognitive networks underlying proneness to auditory hallucinations (AH) across the continuum of psychosis. The PI, Dr. Shinn, is a clinically trained psychiatrist with four years of post-residency training in psychosis functional connectivity (FC) research. She proposes to investigate both structural and dynamic aspects of connectivity, focusing on dorsal anterior cingulate cortex (dACC), auditory cortex (A1), voice perception (Vper), and voice production (Vpro) areas in AH- prone patients across the diagnostic categories of schizophrenia, schizoaffective disorder, bipolar psychosis, and DSM-IV psychotic disorder not otherwise specified (NOS). There is a clinical need to understand AH pathophysiology better, as AH are often distressing and associated with increased suicide risk. While antipsychotic medications can reduce their severity, in 25-30% of patients AH are refractory to antipsychotic medications. More effective interventions targeted at underlying AH pathophysiology are necessary. However, patient heterogeneity presents a major challenge to biological research in this area. Dr. Shinn proposes to directly address the issue of patient heterogeneity by: (a) Taking a dimensional and cross-diagnostic approach. AH are more homogeneous than diagnoses, and the current proposal aims to identify a neurobiological AH signature that transcends diagnosis. (b) Identifying subject- and functionally specific brain regions of interest and conducting analyses at the individual subject level; (c) Using multimodal neuroimaging within a single cohort to generate more cohesive understanding. Her approach, combining stochastic tractography, resting state fMRI (rsfMRI), and fMRI during a cognitive interference task, can inform about structural, baseline, and dynamic task-related aspects of connectivity. Dr. Shinn's hypothesis, which attempts to reconcile conflicting cognitive models of AH, is that AH-prone patients have increased baseline connectivity between A1, Vper, Vpro, and dACC, and an inability to modulate these connections during the auditory Stroop, a task that requires suppression of attention to irrelevant aspects of auditory stimuli. Such tonic hyper- and phasic hypo- connectivity may reflect a network that is biased towards hearing internally generated voices and less able to allocate resources when challenged. The current proposal may provide better understanding of circuitry abnormalities in AH, and expand possibilities for AH treatment using interventions such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), or neurofeedback, with an eye towards personalized medicine approaches. In parallel with the research proposed, Dr. Shinn will engage in multiple career development activities to vertically and horizontally expand her ability to develop mechanistic insights about AH. These include new training in cognitive neuroscience, better understanding of mechanisms involved in auditory and speech/language processing, and a stronger grasp of basic neuroscience. She will also receive advanced training in rsfMRI and new training in stochastic tractography.

描述（由申请人提供）：该K23提案旨在了解精神病连续性的听觉幻觉（AH）的听觉，语音和认知网络。 PI Shinn博士是一名受临床训练的精神病医生，在精神病功能连通性研究（FC）研究中进行了四年的居住后培训。她建议研究连通性的结构和动态方面，重点是前扣带回皮层（DACC），听觉皮层（A1），语音感知（VPER）和语音产生（VPR）和语音产生（VPRO）地区，跨ah-易于诊断，精神分裂症的诊断症状，精神病患者的诊断症状（biporal Inderive），biporly confiraffersistiv nosistiv nosistiv nosistiv nosistiv nishiafe nosistiv。临床需要更好地了解AH病理生理学，因为AH通常令人沮丧，并且与自杀风险增加有关。虽然抗精神病药可以降低其严重程度，但在25-30％的患者中，AH对抗精神病药的难治性。需要采取更有效的针对基本AH病理生理学的干预措施。但是，患者的异质性给该领域的生物学研究带来了重大挑战。 Shinn博士建议通过以下方式直接解决患者异质性问题：（a）采用维度和跨诊断方法。 AH比诊断更均匀，目前的建议旨在确定超越诊断的神经生物学AH标志。（b）识别感兴趣的受试者和功能特定的大脑区域，并在单个受试者水平上进行分析；（c）在单个队列中使用多模式神经影像学以产生更大的理解。在认知干扰任务中，她的方法结合了随机拖拉机，静止状态fMRI（RSFMRI）和fMRI，可以告知连通性的结构，基线和动态任务相关方面。 Shinn博士的假设试图调和AH的矛盾认知模型，是AH容易发生的患者增加了A1，VPER，VPER，VPRO和DACC之间的基线连接性，并且无法在听觉stroop期间调节这些连接，这项任务需要抑制对听觉刺激的不相同方面的注意力。这种补品超级和音阶的低连通性可能反映了一个网络，该网络偏向于听到内部产生的声音，并且在挑战时降低了资源分配资源。当前的提案可以更好地了解AH的电路异常，并使用诸如重复的经颅磁刺激（RTMS），经颅直流电流刺激（TDC）或神经反馈的干预措施扩大AH治疗的可能性，以朝向个性化药物方法。与提出的研究同时，Shinn博士将从事多种职业发展活动，以垂直和水平扩大她开发有关AH机械见解的能力。这些包括对认知神经科学的新培训，对听觉和语音/语言处理所涉及的机制的更好理解，以及对基本神经科学的更强掌握。她还将接受RSFMRI的高级培训和随机拖拉学的新培训。