Efficacy of Personalizing Cognitive Remediation for Schizophrenia by Targeting Impairments in Early Auditory Processing

精神分裂症与认知缺陷有关，这些缺陷对日常功能产生了负面影响。干预措施 改善精神分裂症的认知功能对于限制长期残疾至关重要。认知 精神分裂症的治疗(CR)对认知和功能结果的中等影响程度较低，但 对CR的治疗反应是不同的。对治疗有反应的个体的前瞻性识别 个体化治疗方法仍然是一个尚未满足的挑战。我们的初步研究使用 治疗精神分裂症的个性化CR方法表明，基线早期听觉处理(EAP)，这是 在约一半的精神分裂症患者中受损，是指导治疗的良好神经行为标记物 策略。我们发现，EAP基线受损的人在认知结果上的改善明显更多 当CR包括EAP培训时，这有助于获得更大的功能收益。然而，这不会带来额外的好处 对EAP基线完好无损的人进行这种培训。治疗机制的亚群特异性是 提示听觉加工增益与EAP的认知改善呈正相关 在EAP完好者中，受损与负面或不显著的关联。这些发现 支持在尝试补救更高级别时解决基本听觉处理缺陷的重要性 对语言学习等听觉障碍进行排序。此外，它们还强调了例行评估的必要性 在CR参与者中，EAP的发生率很高，因此治疗可以个性化。来自正在进行的中心资助项目的试点数据 表明临床医生能够评估EAP状态，并使用它来个性化治疗，以包括或 不包括EAP培训。因此，在公共诊所实施这种个性化CR是可行的。 建议的研究采用治疗对照随机设计，首先按EAP对受试者进行分层 状态，然后随机分为EAP增强CR、常规CR或照常治疗。这项研究将是 使用正在进行的中心赠款CR项目的基础设施在社区诊所进行。认知意志 是主要结果，功能能力是次要结果。CR患者的移动脑电检查 参与者将检查对EAP训练的需求和反应的神经生理学标记。调解 分析将检验认知收益是否在EAP收益和功能性收益之间的关系中起中介作用 结果。这将有助于我们理解EAP是大约一半CR的治疗改变机制 并确认不需要对EAP基线完好的CR参与者进行EAP培训。 这项研究的目标是通过识别一种精神分裂症谱系障碍的 用于优化和个性化治疗的可扩展方法。通过促进更好地理解EAP作为 神经行为标记物、早期听觉处理作为改变的机制，以及基本的CR治疗 针对EAP受损的CR参与者，拟议的为期4年的研究将为改进的临床决策提供信息- 就如何最好地提供认知训练做出并指导临床判断。

Schizophrenia is associated with cognitive deficits that negatively impact daily functioning. Interventions that improve cognitive functioning in schizophrenia are critical to limit long-term disability. Cognitive remediation (CR) for schizophrenia has low moderate effect sizes on cognitive and functional outcomes, but therapeutic responses to CR are heterogeneous. Prospective identification of treatment-responsive individuals and individualized treatment approaches remains an unmet challenge. Our preliminary studies using personalized CR approaches for schizophrenia indicate that baseline early auditory processing (EAP), which is impaired in about half of people with schizophrenia, is a good neurobehavioral marker for informing treatment strategy. We found that people with baseline impaired EAP improve significantly more on cognitive outcomes when CR includes EAP training, and this facilitates larger functional gain. However, there is no added benefit to giving this training to people with baseline intact EAP. Subgroup specificity of therapeutic mechanism is suggested by the positive association of auditory processing gain with cognitive improvement among EAP impaired versus the negative or non-significant association among those who are EAP intact. These findings support the importance of addressing basic auditory processing deficits when attempting to remediate higher order auditory impairments such as verbal learning. In addition, they highlight the need for routine assessment of EAP in CR participants, so treatment can be personalized. Pilot data from an ongoing center grant project indicates that clinicians are able to assess EAP status and use it to personalize treatment to either include or exclude EAP training. Thus it is feasible to implement this kind of personalized CR in public clinic settings. The proposed study uses a treatment controlled randomized design, first stratifying subjects by EAP status and then randomizing to EAP enhanced CR, regular CR, or treatment as usual. The study will be conducted in community clinics using the infrastructure of the ongoing center grant CR project. Cognition will be the primary outcome with functional capacity the secondary outcome. Mobile EEG administered to CR participants will examine neurophysiologic markers of need for and response to EAP training. Mediation analysis will examine whether gains in cognition mediate the relationship between gains in EAP and functional outcome. This will inform our understanding of EAP as the therapeutic change mechanism for about half of CR participants and confirm that EAP training need not be given to those CR participants with baseline intact EAP. The goal of this study is to enhance CR outcomes in schizophrenia spectrum disorders by identifying a scalable approach to optimizing and personalizing treatment. By facilitating a better understanding of EAP as a neurobehavioral marker, early auditory processing as mechanism of change, and the essential CR treatment targets for EAP impaired CR participants, the proposed 4-year study will inform improved clinical decision- making and guide clinical judgment about how to best provide cognitive training.