Corollary Discharge Dysfunction in Schizophrenia: ERPs and EEG

抽象的。精神分裂症是一种泛脑性疾病，几乎影响到所有的形态、功能和大脑。 所研究的地区。虽然每种症状和功能都可能是由于其自身的故障机制造成的，但简朴 鼓励我们找到一个基本的机制，可能是至少一些症状的根源。 越来越多的证据表明，精神分裂症的特征是传出复制/推论功能障碍 通常允许我们无意识地识别和忽视由此产生的感觉的放电机制 来自我们自己的行动。这种功能障碍可能会引起细微但普遍的感觉/知觉异常 精神分裂症患者，改变他们对自己公开和隐蔽行为的体验，以及他们的 与环境的互动。它还可能导致幻觉、妄想和 甚至是与人交往和参与活动的欲望。 在最初的资助期间，我们开发了神经生理学范式来研究运动感觉进食-- 言语-听觉系统中的前向过程，或传出复制/必然放电机制，以及 表明这些过程在慢性精神分裂症中是缺乏的。具体地说，我们能够观察到神经 谈话中的反应，这表明了推论的成功行动的后果 出院。我们还开发了一种在说话前观察同步神经活动的方法，它 我们认为这反映了传出副本在行动中的作用。最近，我们将这项神经生理学研究扩展到 躯体感觉系统，我们再次发现了运动感觉前馈过程缺陷的证据 精神分裂症。如果这一基本机制的功能障碍是可靠、有效的，而不是抗精神病药物的结果 药物，它可能代表了一类主要的新的电生理措施，对基本面敏感 和普遍存在的精神分裂症的病理生理过程。因此，这些措施可能是新颖的。 用于识别精神分裂症风险基因的神经生理学内表型。他们也可能是 在精神分裂症的新治疗方法的开发和测试中用作结果衡量标准。 为了开始解决这些重要的可能性，我们建议继续我们对传出的研究 精神分裂症的复制/推论放电系统及其异常，跨越听觉、躯体感觉和 视觉形态。我们建议在疾病的早期和更慢性的阶段对患者进行评估 评估疾病持续时间的影响。我们还将评估精神分裂症患者未受影响的一级亲属 患者，以确定这些必然的放电异常是否反映了遗传风险 生病了。最后，对神经外科患者植入皮质电极的拟议研究将使我们能够 定位这些传出复制/推论放电前馈信号的来源和目的地。这 信息将帮助我们更好地定位大脑区域和回路，这些区域和回路可能是必然放电的基础 精神分裂症的功能障碍。叙事性。我们已经开发了一种大脑成像技术来检测可能是元素的缺陷 一种神经生物学机制，使我们能够将自己的想法和行为与他人的想法和行为区分开来。 我们希望确定它是否在家庭中运行，是否在疾病的早期出现，以及是否稳定可靠。

Abstract. Schizophrenia is a pan-cerebral illness, affecting almost every modality, function, and brain region studied. While each symptom and function might be due to its own failed mechanism, parsimony encourages us to find an elemental mechanism that could be at the root of at least some of the symptoms. Evidence is accumulating that schizophrenia is characterized by dysfunction of efference copy/corollary discharge mechanisms that normally allow us to unconsciously recognize and disregard sensations resulting from our own actions. This dysfunction may give rise to subtle but pervasive sensory/perceptual aberrations in schizophrenic patients, altering their experience of their own overt and covert actions, as well as their interactions with the environment. It may also contribute to symptoms such as hallucinations, delusions, and even the desire to engage with people and in activities. In the initial funding period, we developed neurophysiological paradigms to study motor-sensory feed- forward processes, or efference copy/corollary discharge mechanisms, in the speech-auditory system, and showed these processes to be deficient in chronic schizophrenia. Specifically, we were able to observe neural responses during talking, which made evident the consequences of the successful action of the corollary discharge. We have also developed a method to observe synchronous neural activity preceding talking, which we believe reflects the efference copy in action. Recently, we extended this neurophysiological research to the somatosensory system, and again we find evidence of deficient motor-sensory feedforward processes in schizophrenia. If dysfunction of this elementary mechanism is reliable, valid, and not the result of antipsychotic medications, it might represent a major new class of electrophysiological measures sensitive to a fundamental and ubiquitous pathophysiological process in schizophrenia. Accordingly, these measures may serve as novel neurophysiological endophenotypes for identifying genes that confer risk for schizophrenia. They may also be useful as outcome measures during the development and testing of novel treatments for schizophrenia. To begin to address these important possibilities, we propose to continue our studies of the efference copy/corollary discharge system and its abnormalities in schizophrenia, across auditory, somatosensory and visual modalities. We propose to assess patients during early stages of the illness and more chronic phases to assess the effects of illness duration. We will also assess unaffected first-degree relatives of schizophrenic patients in order to determine whether these corollary discharge abnormalities reflect genetic risk for the illness. Finally, proposed studies of neurosurgery patients implanted with cortical electrodes will allow us to localize the origins and destinations of these efference copy/corollary discharge feed-forward signals. This information will help us to better localize the brain regions and circuitry that may underlie corollary discharge dysfunction in schizophrenia. Narrative. We have developed a brain imaging technique to detect deficits in what may be an elemental neurobiological mechanism that allows us to distinguish our own thoughts and actions from those of others. We hope to determine whether it runs in families, is present early in the illness, and is stable and reliable.