Real time fMRI feedback and auditory processing in schizophrenia

描述（由申请人提供）：听觉言语幻觉（AH）长期以来一直是精神分裂症（SZ）精神病学的标志，也是其主要诊断特征之一（Andreasen和Flaum，1991; DSM-IV）。研究表明，AH涉及的大脑区域参与语言处理的不同方面。该脑网络包括颞叶皮层，尤其是上级颞回（STG）、前扣带回（ACC）、额下回（IFG）和颞顶交界（TPJ）。直到最近， AH主要通过抗精神病药物控制，但通常无效。在这个应用程序中，我们建议使用一个尖端的生物反馈方法的实时功能成像神经反馈（rt-fMRI），以减少AH的频率，并更好地了解大脑过程中涉及AH。我们采用Hugdahl 2009年的AH模型，根据该模型，AH是由言语自我监控、选择性注意和听觉感知过程异常引起的。我们专注于听觉皮层的作用，特别是STG，作为治疗SZ AH的神经反馈训练的目标区域。基于现有文献，我们认为STG中的改进功能将使AH体验中涉及的整个网络规范化。我们预测STG（以及形成AH网络的区域：IFG，ACC和TPJ）的激活将由于从该区域接收反馈而增加，这将导致在识别自我/其他声音的任务上有更好的表现，如通过rt-fMRI训练前后的fMRI激活水平以及减少阳性症状，特别是AH。rt-fMRI神经反馈依赖于计算机技术的最新进展，该技术允许受试者看到选定脑区的激活水平，并在提供的训练后调节其激活。受试者被教导在基于激活任务选择的特定大脑区域内上调或下调fMRI信号。重要的是，只有当受试者从他/她的目标区域接收反馈时，报告的激活变化才是可能的，而不是当她/他从不同的受试者或与目标区域不同的区域（假）接收反馈时。最近已经证明，这种方法可能有助于许多临床疾病，其中包括精神分裂症（Haller 2010; Sitaran 2011;林登2012;Veit 2009; Hartwell 2012; Li 2012，Ruiz 2011）。在这项研究中，我们计划研究30名慢性SZ患者和30名正常对照（NC）个体（其中一半将接受真实的反馈，另一半将接受假fMRI反馈）。我们将使用功能磁共振成像（包括两个连接性的措施）和临床措施的有效性rt-fMRI反馈。基于现有的文献和我们的初步数据，我们预测，我们将成功地改善STG和目标网络内的听觉处理，这将导致临床症状的改善，特别是AH的频率。

DESCRIPTION (provided by applicant): Auditory verbal hallucinations (AH) have long been a hallmark of schizophrenia (SZ) symptomatology and one of its major diagnostic features (Andreasen and Flaum, 1991; DSM-IV). It has been demonstrated that the brain regions implicated in AH are involved in different aspects of language processing. This brain network includes the temporal cortex and especially the superior temporal gyrus (STG), anterior cingulate (ACC), inferior frontal gyrus (IFG), and temporo-parietal junction (TPJ). Until recently, AH were primarily controlled with antipsychotic medication which was often ineffective. In this application, we propose to use a cutting-edge biofeedback method of real-time functional imaging neuro-feedback (rt-fMRI) to reduce the frequency of AH and to better understand brain processes involved in AH. We adopt the Hugdahl 2009 model of AH according to which AH result from abnormalities in self-monitoring of speech, in selective attention and in auditory perceptual processes. We focus on the role of auditory cortex, specifically the STG, as a target area of neuro-feedback training for the treatment of AH in SZ. Based on existing literature, we posit that that improved function in the STG will normalize the entire network involved in the experience of AH. We predict that the activation in the STG (and regions forming AH network: IFG, ACC, and TPJ) will increase as a result of receiving feedback from that region which will lead to a better performance on the task of recognizing self/other voice as measured by fMRI activation levels pre-and post-rt-fMRI training and by reduction in positive symptoms and especially AH. The rt-fMRI neuro-feedback relies on recent advances in computer technology that allows subjects to see the level of activation in the selected brain region and to regulate ths activation following the training provided. Subjects are taught to up-regulate or down-regulate fMRI signal within a specific brain region selected based on the activation task. Importantly, reported activation changes are possible only if the subject receives a feedback from his/her target area and not when she/he receives it from a different subject or a different area than the target one (sham). It has been recently demonstrated that this approach may be helpful in many clinical conditions, among them schizophrenia (Haller 2010; Sitaran 2011;Linden 2012;Veit 2009; Hartwell 2012; Li 2012, Ruiz 2011). In this study we propose to study 30 chronic SZ patients and 30 normal control (NC) individuals (half of them will receive real and half will receive a sham fMRI feedback). We will use both fMRI (including two measures of connectivity) and clinical measures of the effectiveness of the rt-fMRI feedback. Based on the existing literature and our preliminary data, we predict that we will successfully improve auditory processing within the STG and within the targeted network and that it will lead to improvement in the clinical symptoms and especially in the frequency of AH.