Corollary Discharge Dysfunction in Schizophrenia: ERPs and EEG

抽象的。精神分裂症是一种泛脑疾病，影响几乎每一种形态，功能和大脑 区域研究。虽然每个症状和功能可能是由于其自身的失败机制，吝啬 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 放电机制，通常允许我们无意识地识别和忽视的感觉， 我们自己的行为。这种功能障碍可能会引起微妙但普遍的感觉/知觉畸变， 精神分裂症患者，改变他们对自己的公开和隐蔽行动的体验，以及他们的 与环境的相互作用。它也可能导致幻觉，妄想， 甚至是与人交往和参与活动的愿望。 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-感觉饲料- 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缺乏。具体来说，我们能够观察到神经 在谈话中的反应，这使得明显的后果，成功的行动的必然结果 放电我们还开发了一种方法来观察说话前的同步神经活动， 我们相信这反映了行动中的传出副本。最近，我们将这项神经生理学研究扩展到了 躯体感觉系统，我们再次发现缺乏运动感觉前馈过程的证据， 精神分裂症如果这种基本机制的功能障碍是可靠的、有效的，而不是抗精神病药物的结果， 药物，它可能代表了一个重要的新类别的电生理措施敏感的基本 和普遍存在的病理生理过程。因此，这些措施可以作为新的 神经生理学内表型，用于识别赋予精神分裂症风险的基因。它们也可以 在精神分裂症的新治疗的开发和测试期间作为结果测量是有用的。 为了开始解决这些重要的可能性，我们建议继续我们的研究， 复制/必然放电系统及其在精神分裂症中的异常，跨越听觉、躯体感觉和 视觉形式我们建议在疾病的早期阶段和较慢性的阶段评估病人， 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， 病最后，对植入皮层电极的神经外科患者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起源和目的地。这 这些信息将帮助我们更好地定位大脑区域和电路， 精神分裂症的功能障碍叙事。我们已经开发出一种大脑成像技术来检测可能是元素的缺陷 这是一种神经生物学机制，使我们能够将自己的思想和行为与他人的思想和行为区分开来。 我们希望确定它是否在家庭中运行，在疾病的早期出现，并且是稳定和可靠的。

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.