Neuroimaging Different Cognitive-Control Processes in Normals and Schizophrenics

描述(申请人提供)：我们的目标是确定在正常情况下组成不同类型“认知控制”的认知和神经过程，并具体说明这些过程在精神分裂症患者中是如何受损的，从而导致重要的行为缺陷。以前对精神分裂症认知控制缺陷的研究在告诉我们有关特定神经回路的信息方面是有限的，因为这些研究通常使用需要多个控制过程的单一任务。在某种程度上，先前对正常的研究也存在同样的局限性。我们提出了一种不同的策略：在使用功能磁共振成像(FMRI)对他们的大脑进行扫描的同时，我们将让精神分裂症患者和正常对照组执行多项认知控制任务，其中每项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，这些任务基于之前对正常的发现，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再认测验的变体，包括：(1)忽略任务，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工作记忆中已经存在的信息；(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。在三个fMRI会议的过程中，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。行为数据将准确描述精神分裂症患者三个不同的控制过程--知觉选择、工作记忆选择和反应抑制--各自完好无损或受损的程度。FMRI数据应该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，并告诉我们在患者表现出行为缺陷的控制任务中受到损害的电路。我们的初步行为发现表明，患者在抑制和停止方面受到损害，但在忽视方面没有受到损害--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，患者的抑制功能受损伴随着左半球前额叶皮质的异常激活(而不仅仅是激活减少)。我们预计我们的fMRI实验将进一步揭示：当患者在抑制状态下表现出异常活动时，他们在忽略状态下的神经活动可能相对正常；当正常患者在抑制状态下激活左脑PFC回路时，他们在停止状态下激活右半球回路，而这两个回路在精神分裂症患者中都表现出异常活动。

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.