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能够参照上下文和偶发信息来滴定我们对刺激和事件的反应。因此，我们从简单的反应和我们周围环境的特质中解脱出来。前额背外侧核(DLPFC)由于其与皮质感觉区的丰富联系，具有独特的位置，便于对感觉输入的认知控制和对这些输入的高级处理。人类和动物研究表明，DLPFC在认知控制中起着至关重要的作用。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为DLPFC的功能架构带来了新的见解，建立在使用其他技术进行的动物和人类研究结果的基础上，并对其进行补充。研究DLPFC功能及其对“自下而上”过程的调控具有深远的临床意义。正如病变患者所证明的那样，DLPFC的功能障碍可能会导致毁灭性的情况。精神分裂症的病理生理学可能涉及许多脑区和认知过程。然而，有几条证据表明，DLPFC功能障碍在其许多症状的阐述中起着中心作用。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的重要第一步。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调节感觉输入服务于更高级别认知过程的精确神经机制。然后，我将研究一组精神分裂症患者的这些过程，以记录DLPFC的功能障碍。我计划使用复杂的神经成像和分析技术进行这些研究，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.