fMRI Investigation of Active Maintenance in Schizophrenia

描述（由申请人提供）：人类行为的一个显著特征是我们有能力根据上下文和偶然信息来调整我们对刺激和事件的反应。因此，我们从简单的反射和我们周围环境的特质中解脱出来。背侧前额叶（DLPFC）由于其与皮层感觉区域的丰富联系，处于独特的位置，有助于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，认知控制发挥作用的具体机制仍有待阐明。强大的神经成像技术的出现，使人们对DLPFC的功能结构有了新的认识，并在动物和使用其他技术的人类研究结果的基础上进行了补充。研究DLPFC功能及其对“自下而上”过程的调节具有深远的临床意义。根据病变患者的记录，DLPFC功能障碍可导致毁灭性的疾病。精神分裂症的病理生理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处于中心地位。与精神分裂症基因的发现类似，精神分裂症认知过程改变的神经相关图谱是发现这种疾病新疗法过程中重要的第一步。我提出了一系列平行的研究，首先，在健康的成年人中，阐明DLPFC对服务于高阶认知过程的感觉输入的调节所涉及的精确神经机制。然后，我将在一组精神分裂症患者中研究这些过程，以证明DLPFC功能障碍。我计划使用复杂的神经成像和分析技术来进行这些研究，以检查DLPFC与视觉系统的动态相互作用。

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.