Neuroimaging Different Cognitive-Control Processes in Normals and Schizophrenics

描述（由申请人提供）：我们的目标是确定正常情况下构成不同类型“认知控制”的认知和神经过程，并详细说明这些过程如何在精神分裂症患者中受到损害，从而导致重要的行为缺陷。先前关于精神分裂症认知控制缺陷的研究，由于研究通常使用需要多个控制过程的单一任务，因此它们只能告诉我们所涉及的特定神经回路。在某种程度上，同样的局限性也适用于以前的正常研究。我们提出了一个不同的策略：在使用功能性磁共振成像（fMRI）扫描他们的大脑的同时，我们将让精神分裂症患者和正常对照组执行多个认知控制任务，其中每个任务都是相对纯过程的，但总的来说，这些任务跨越了认知控制的大部分领域。我们将使用三个最先进的认知神经科学任务，这些任务基于以前的研究结果，正常应该隔离特定的控制过程及其潜在的神经回路。这些任务都是工作记忆的项目识别测试的变体，包括：（1）忽略任务，其中参与者在信息进入工作记忆之前选择性地忽略信息;（2）抑制任务，其中参与者选择性地抑制已经在工作记忆中的信息;（3）停止任务，其中参与者抑制已经准备好的对工作记忆探测的反应。在三次功能磁共振成像过程中，我们将测试24名精神分裂症患者和24名对照组在所有三项任务上的表现。行为数据将提供一个精确的描述，在精神分裂症中，三个不同的控制过程--知觉选择、工作记忆选择和反应抑制--中的每一个都是完整的或受损的。fMRI数据应该揭示正常认知控制过程背后的三个重叠神经网络，并告诉我们在患者表现出行为缺陷的控制任务中受损的回路。我们的初步行为研究结果表明，患者在抑制和停止方面受损，但在忽略方面没有受损-这表明他们在认知控制方面没有普遍缺陷。我们的初步fMRI数据表明，患者抑制功能的受损伴随着左半球前额叶皮层的异常激活（不仅仅是较少的激活）。我们期望我们的功能磁共振成像实验将进一步揭示：当患者在抑制中表现出异常活动时，他们在忽略中的神经活动可能相对正常;当正常激活抑制中的左PFC回路时，他们激活停止中的右半球回路，并且这两个回路在精神分裂症患者中表现出异常活动。

DESCRIPTION (provided by applicant): Our goals are to determine the cognitive and neural processes that comprise different kinds of "cognitive control" in normal, and to specify how these processes are compromised in patients with schizophrenia, leading to important behavioral deficits. Prior studies of cognitive-control deficits in schizophrenia are limited in wht they can tell us about the specific neural circuits involved because the studies typically use a single task that requires multiple control processes. To some extent, the same limitation is true of prior studies with normal. We propose a different strategy: while having their brains scanned using functional Magnetic Resonance Imaging (fMRI), we will have patients with schizophrenia and normal controls perform multiple cognitive control tasks, where each task is relatively process-pure but taken together the tasks span much of the domain of cognitive control. We will use three state-of-the-art cognitive-neuroscience tasks that based on previous findings with normal should isolate specific control processes and their underlying neural circuitry. The tasks are all variants of the Item-Recognition test of working memory, and include the: (1) Ignore task, in which the participant selectively ignores information before it enters working memory; (2) Suppress task, in which the participant selectively suppresses information that is already in working memory; and (3) Stop task, in which the participant inhibits an already prepared response to a probe of working memory. Over the course of three fMRI sessions, we will test 24 patients with schizophrenia and 24 controls on all three tasks. The behavioral data will provide a precise description of the degree to which each of three different control processes--perceptual selection, working-memory selection, and response inhibition--are intact or impaired in schizophrenia. The fMRI data should reveal three overlapping neural networks that underlie normal cognitive- control processes, as well as inform us about the circuits that are compromised in those control tasks in which the patients show behavioral deficits. Our preliminary behavioral findings indicate that the patients are impaired on Suppress and Stop but not on Ignore--indicating that they do not have a general deficit in cognitive control. Our preliminary fMRI data indicate that the patients' impairment on Suppress is accompanied by abnormal activation (not merely less activation) in the left-hemisphere prefrontal cortex. We expect that our fMRI experiments will further reveal that: while patients show abnormal activity in Suppress, their neural activity in Ignore may be relatively normal; and while normal activate a left PFC circuit in Suppress, they activate a right- hemisphere circuit in Stop, and both these circuits show abnormal activity in patients with schizophrenia.