Cortical Plasticity Across Phase of Illness in Schizophrenia

项目摘要 精神分裂症患者患有明显的认知障碍，这是高度预测社会， 职业和社区功能。因此，认知障碍是干预的主要目标。 皮质可塑性的缺失被认为是认知障碍的基础。但因为是 直到最近才能在体内评估人类皮质可塑性，皮质可塑性的程度 是否影响精神分裂症尚不清楚。此外，我们还不知道大脑皮层的可塑性是否会随着时间的推移而改变。 病的阶段。动物研究表明，大脑皮层的可塑性随着年龄的增长而下降。很可能多 精神分裂症、皮质可塑性的正常成熟下降与疾病协同作用 疾病发展过程中的病理生理学。因此，皮质可塑性可能较低， 在疾病的早期阶段受到损害。最后，人们对这种行为在现实世界中的后果知之甚少。 精神分裂症患者大脑皮层可塑性异常K23项目符合战略 在NIMH战略计划中概述，特别是战略1.1.，来描述与 复杂的行为，策略2.1，描述大脑成熟的发展轨迹， 行为维度，以了解不同人群中精神疾病的根源， 2.2，确定临床上有用的生物标志物，预测疾病轨迹的变化。具体而言是 提案涉及申请人与不同的杰出研究人员团队密切合作的计划， 神经科学，临床和发展心理学以及生物统计学方面的专业知识，以研究 神经发育框架内精神分裂症的皮质可塑性。使用新开发的脑电图 范例，允许非侵入性评估可塑性在人类感觉皮层，我们将研究 近期发作精神分裂症、慢性精神分裂症和匹配的非精神病对照个体 参与者调查：1）精神分裂症中皮质可塑性是否异常，2）皮质可塑性是否异常， 可塑性随疾病阶段而变化，和3）精神分裂症中皮层可塑性的潜在相关性， 包括知觉处理和高阶认知的基于表现的任务，以及日常功能。 这些发现将为该领域提供有关受损神经基础的发展过程的信息。 精神分裂症的认知，并将告知可塑性为基础的干预措施，以改善这一人群的认知。 在先进的脑电图分析方法和发展精神病理学的指导培训将允许 申请人开发一个独立的，跨学科的临床研究计划，结合 电生理学和行为学方法研究严重精神病理学患者的认知和功能 在整个生命周期中。

PROJECT SUMMARY Individuals with schizophrenia suffer from marked cognitive impairment, which is highly predictive of social, occupational, and community functioning. As a result, cognitive impairment is a prime target for intervention. Abnormalities in cortical plasticity are hypothesized to underlie cognitive impairment. However, because it was not possible to evaluate human cortical plasticity in vivo until very recently, the extent to which cortical plasticity is impacted in schizophrenia is unclear. Furthermore, it is unknown whether cortical plasticity changes over phase of illness. Animal studies indicate that cortical plasticity declines with age. It is possible that in schizophrenia, normative maturational declines in cortical plasticity interact synergistically with disease pathophysiology over the developmental course of the illness. Thus, cortical plasticity may be less compromised in the early phase of illness. Finally, little is known about the real-world consequences of abnormal cortical plasticity for individuals with schizophrenia. This K23 project is consistent with strategies outlined in the NIMH Strategic Plan, particularly Strategy 1.1., to describe the neural circuits associated with complex behaviors, Strategy 2.1, to characterize the developmental trajectories of brain maturation and dimensions of behavior to understand the roots of mental illnesses across diverse populations, and Strategy 2.2, to identify clinically useful biomarkers that predict change across the trajectory of illness. Specifically, the proposal involves a plan for the applicant to work closely with a diverse team of distinguished researchers with expertise in neuroscience, clinical and developmental psychology, and biostatistics to investigate biomarkers of cortical plasticity in schizophrenia within a neurodevelopmental framework. Using newly-developed EEG paradigms that permit non-invasive assessment of plasticity in the human sensory cortex, we will study individuals with recent-onset schizophrenia, chronic schizophrenia, and matched non-psychiatric comparison participants to investigate: 1) whether cortical plasticity is abnormal in schizophrenia, 2) whether cortical plasticity changes over phase of illness, and 3) potential correlates of cortical plasticity in schizophrenia, including performance-based tasks of perceptual processing and higher-order cognition, and daily functioning. The findings will inform the field about the developmental course of the neural underpinnings of impaired cognition in schizophrenia, and will inform plasticity-based interventions to improve cognition in this population. Mentored training in advanced EEG analytic methods and developmental psychopathology will permit the applicant to develop an independent, interdisciplinary program of clinical research that combines electrophysiology and behavioral methods to investigate cognition and functioning in severe psychopathology across the lifespan.