fMRI Investigation of Active Maintenance in Schizophrenia

描述（由申请人提供）：人类行为的一个显着特征是我们能够参考上下文和偶然信息来滴定我们对刺激和事件的反应。因此，我们摆脱了简单的反射和我们周围环境的特质。背外侧前额叶（DLPFC），由于其与皮层感觉区的丰富联系，是独特的位置，以促进对感觉输入的认知控制和这些输入的高阶处理。人类和动物研究已经证明了DLPFC在认知控制中的重要作用。然而，认知控制的具体机制仍有待阐明。强大的神经成像技术的出现，导致了新的见解DLPFC的功能结构，建立和补充的结果从动物，以及使用其他技术的人类研究。对DLPFC功能及其对“自下而上”过程的调节的研究具有深远的临床意义。DLPFC的功能障碍可能导致破坏性的条件，如病变患者的记录。精神分裂症的病理生理学可能涉及许多大脑区域和认知过程。然而，一些证据表明DLPFC功能障碍在其许多症状的阐述中具有中心地位。类似于精神分裂症基因的发现，精神分裂症中认知过程改变的神经相关性的映射是发现这种疾病新疗法的重要的第一步。我提出了一系列平行研究，首先在健康成年人中进行，以阐明DLPFC调节感觉输入以服务于高阶认知过程的精确神经机制。然后，我将在一组精神分裂症患者中研究这些过程，以记录DLPFC的功能障碍。我计划进行这些研究，采用先进的神经成像和分析技术，以检查动态相互作用的DLPFC与视觉系统。

DESCRIPTION (provided by applicant): A distinguishing feature of human behavior is our ability to titrate our responses to stimuli and events with reference to contextual and contingent information. Thus, we are freed from simple reflexes and the idiosyncrasies of our immediate environment. The dorsalateral prefrontal (DLPFC), owing to its abundant connections with cortical sensory areas, is uniquely situated, to facilitate cognitive control over sensory inputs and higher order processing of these inputs. Human and animal studies have demonstrated the crucial involvement of the DLPFC in cognitive control. However, the specific mechanism by which cognitive control is exerted, remains to be elucidated. The emergence of powerful neuroimaging techniques have led to new insights into the functional architecture of the DLPFC, building on and complementing results obtained from animal, as well as, human studies using other techniques. The study of DLPFC function and its modulation of "bottom up" processes has profound clinical implications. The dysfunction of the DLPFC can lead to devastating conditions, as documented by lesion patients. The pathophysiology of schizophrenia likely involves many brain regions and cognitive processes. However, several lines of evidence point to the centrality of of the DLPFC dysfunction in the elaboration of many of its symptoms. Analogous to the discovery of schizophrenia genes, the mapping of the neural correlates of altered cognitive processes in schizophrenia is an important first step in the process of discovering new treatments for this illness. I propose a parallel series of studies, first, in healthy adults, to elucidate the precise neural mechanisms involved in DLPFC modulation of sensory inputs in the service of higher order cognitive processes. I will then study these processes in a group of schizophrenics to document dysfunction of the DLPFC. I plan to conduct these studies employing sophisticated neuroimaging and analytical techniques to examine the dynamic interactions of the DLPFC with the visual system.