Cortical Plasticity Across Phase of Illness in Schizophrenia

项目总结 精神分裂症患者患有显著的认知障碍，这对社交活动具有很高的预测性， 职业和社区功能。因此，认知障碍是干预的主要目标。 皮质可塑性的异常被认为是认知障碍的基础。然而，因为它是 直到最近，才有可能在体内评估人类皮质的可塑性，皮质可塑性的程度 是否受到精神分裂症的影响尚不清楚。此外，尚不清楚皮质可塑性是否会发生变化。 疾病的阶段。动物研究表明，皮质的可塑性随着年龄的增长而下降。有可能在 精神分裂症，正常成熟的皮质可塑性下降与疾病协同作用 疾病发展过程中的病理生理学。因此，皮质的可塑性可能会降低。 在疾病的早期阶段就妥协了。最后，人们对这一现象的现实后果知之甚少。 精神分裂症患者的皮质可塑性异常。这个K23项目与战略是一致的 在NIMH战略计划，特别是战略1.1中概述，以描述与 复杂行为，策略2.1，描述大脑成熟和发育轨迹 了解不同人群精神疾病根源的行为维度和策略 2.2，确定临床上有用的生物标志物，预测疾病发展轨迹的变化。具体地说， 提案涉及一项计划，让申请人与不同的杰出研究人员团队密切合作， 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，以研究糖尿病的生物标志物 神经发育框架内精神分裂症患者的皮质可塑性。使用新开发的脑电 允许对人类感觉皮质的可塑性进行非侵入性评估的范例，我们将研究 新近发病的精神分裂症、慢性精神分裂症和匹配的非精神病学比较 参与者调查：1)精神分裂症患者皮质可塑性是否异常，2)皮质可塑性是否异常 疾病阶段的可塑性变化，以及3)精神分裂症皮质可塑性的潜在相关性， 包括基于表现性的知觉加工和高级认知任务，以及日常功能任务。 这些发现将使该领域了解受损的神经基础的发育过程。 精神分裂症患者的认知，并将为基于可塑性的干预措施提供信息，以改善这一人群的认知能力。 先进的脑电分析方法和发展精神病理学的指导培训将使 申请者开发一项独立的、跨学科的临床研究计划，将 电生理学和行为学方法研究严重精神病患者的认知和功能 在整个生命周期内。

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.