Neuroimaging Different Cognitive-Control Processes in Normals and Schizophrenics

描述（由申请人提供）：我们的目标是确定在正常情况下构成不同类型“认知控制”的认知和神经过程，并说明这些过程如何在精神分裂症患者中受到损害，导致重要的行为缺陷。先前对精神分裂症患者认知控制缺陷的研究在告诉我们具体的神经回路方面是有限的，因为这些研究通常使用单一任务，需要多个控制过程。在某种程度上，同样的局限性也适用于以往的正常研究。我们提出了一种不同的策略：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者执行多个认知控制任务，其中每个任务都是相对纯粹的过程，但综合起来，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，基于先前的研究结果，正常的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项目识别测试的变体，包括：(1)忽略任务，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，即被试选择性地抑制已存在于工作记忆中的信息；(3)停止任务，即参与者对工作记忆的探测抑制已经准备好的反应。在三次功能磁共振成像的过程中，我们将测试24名精神分裂症患者和24名对照组的所有三项任务。行为学数据将提供对精神分裂症患者三种不同控制过程（知觉选择、工作记忆选择和反应抑制）中每一种控制过程完好或受损程度的精确描述。功能磁共振成像数据将揭示三个重叠的神经网络，它们是正常认知控制过程的基础，并告诉我们在控制任务中受损的回路，在这些控制任务中，患者表现出行为缺陷。我们的初步行为研究结果表明，患者在“抑制”和“停止”上受损，但在“忽视”上没有受损，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，患者在抑制上的损伤伴随着左半球前额皮质的异常激活（不仅仅是激活减少）。我们期望我们的fMRI实验将进一步揭示：当患者在Suppress中表现出异常活动时，他们在Ignore中的神经活动可能相对正常；正常人在“抑制”阶段激活左PFC回路，而在“停止”阶段激活右半球回路，精神分裂症患者的这两个回路都表现出异常活动。

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.