Neural Impact of Cognitive Remediation for Schizophrenia in a Randomized Trial

描述(由申请人提供)：患有精神分裂症和相关精神疾病的患者会出现各种幻觉、妄想和组织紊乱。虽然这些症状中的许多都是破坏性的，但这种疾病的认知障碍与心理社会功能低下关系最大。虽然解决认知障碍的药物治疗对精神分裂症患者几乎没有效果，但认知补救训练已被证明能改善认知和功能。以前对接受认知修复的患者进行的成像研究发现，前额叶激活增加与认知和功能改善有关，但尚不清楚神经连接的变化是否可以更好地表征和预测认知和功能能力的变化。目前的提案将检查精神分裂症患者接受认知治疗的三盲安慰剂对照试验前后的情况。我将首先重复之前的发现，证明认知补救导致前额叶激活和功能连通性的改善，但进一步确定这些变化中哪些最能支持认知和功能结果的变化。这些分析将集中在一般线性模型(GLM)中的功能激活和通过独立成分分析(ICA)测量的功能连接性。我还将研究在静止状态下测量的内在连通性，以确定神经可塑性是否适用于不存在任务需求的情况。这将使我们更好地了解认知修复的神经机制和神经可塑性的程度。以前的发现也发现了精神分裂症患者的行为标记物，可以预测认知治疗后积极的功能变化。然而，目前尚不清楚这些标志物是否也可以预测神经可塑性。在这项建议的第二个目标中，我将确定训练前的认知、心理社会功能和动机是否可以预测认知补救后的神经可塑性变化。在这一目标的第二部分，我将研究相反的效果，确定训练前的神经激活是否预示着认知、功能或动机状态的行为变化。最后，我将使用一个单独的 从多点安慰剂对照认知修复试验中收集的数据集，以复制 这些结果。这项提案的发现将确定支持精神分裂症认知补救训练取得积极结果的神经机制。

DESCRIPTION (provided by applicant): Patients suffering from schizophrenia and related psychotic illnesses suffer from a varied presentation of hallucinations, delusions, and disorganization. While many of these symptoms are disruptive, it is the cognitive impairments of the illness that are most strongly associated with poor psychosocial functioning. While pharmacological treatments to address cognitive impairments have shown little effect for patients with schizophrenia, cognitive remediation training has been demonstrated to offer cognitive and functional improvements. Previous imaging studies of patients who have undergone cognitive remediation have found increased prefrontal activation associated with cognitive and functional improvements, but it is unclear whether changes in neural connectivity may better characterize and predict changes in cognitive and functional ability. The current proposal will examine schizophrenia patients before and after undergoing a triple blind placebo controlled trial of cognitive remediation. I will first replicate previous findings, demonstrating hat cognitive remediation leads to improvements in prefrontal activation and functional connectivity, but further determine which of these changes best supports changes in cognitive and functional outcome. These analyses will focus on functional activation in a general linear model (GLM) and functional connectivity as measured by independent components analysis (ICA). I will also examine intrinsic connectivity, measured at rest, to determine whether neural plasticity generalizes to instances where task demands are not present. This will allow us to better understand the neural mechanisms and extent of neural plasticity from cognitive remediation. Previous findings have also identified behavioral markers in patients with schizophrenia that predict positive functional change from cognitive remediation. However, it is not yet known whether these markers may also predict neural plasticity. In the second aim of this proposal I will determine whether pre-training cognition, psychosocial functioning, and motivation are predictive of neuro-plastic changes from cognitive remediation. In a second part to this aim, I wil examine the opposite effect, determining whether pre-training neural activation is predictive of behavioral changes in cognitive, functional, or motivational status. Finally, I will use a separate set of data collected from a multi-site placebo-controlled cognitive remediation trial to replicate these results. Findings from this proposal will identify the neural mechanisms that support positive outcomes from cognitive remediation training for schizophrenia.