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，对日常功能产生负面影响。干预措施 改善精神分裂症患者认知功能对于限制长期残疾至关重要。认知 精神分裂症的补救（CR）对认知和功能结局的影响较小，但 对CR的治疗反应是不均匀的。治疗应答个体的前瞻性识别 个体化治疗方法仍然是一个未解决的挑战。我们的初步研究使用 精神分裂症的个性化CR方法表明，基线早期听觉处理（EAP）， 在大约一半的精神分裂症患者中， 战略我们发现，基线EAP受损的人在认知结果方面的改善明显更多 当CR包括EAP训练时，这有助于更大的功能增益。但是，没有额外的好处 对那些EAP正常的人进行这种训练。治疗机制的亚组特异性为 这是由EAP中听觉处理增益与认知改善之间的正相关性提出的 受损与消极或非显着的关联在那些谁是EAP完整。这些发现 支持解决基本的听觉处理缺陷的重要性时，试图补救较高 听觉障碍，如语言学习。此外，它们还强调需要进行例行评估 CR参与者的EAP，因此治疗可以个性化。来自一个正在进行的中心赠款项目的试点数据 表明临床医生能够评估EAP状态，并使用它来个性化治疗， 排除EAP培训。因此，在公共诊所环境中实施这种个性化CR是可行的。 该研究采用治疗对照随机设计，首先根据EAP对受试者进行分层 状态，然后随机分配至EAP增强CR、常规CR或常规治疗。本研究将 在社区诊所使用正在进行的中心赠款CR项目的基础设施进行。认知将 是主要结果，功能能力是次要结果。对CR进行移动的EEG 参与者将检查EAP训练的需要和反应的神经生理学标志物。调解 分析将检查认知的增益是否介导EAP增益和功能之间的关系。 结果。这将告知我们对EAP作为约一半CR的治疗改变机制的理解 参与者，并确认EAP培训不需要给予那些基线完好EAP的CR参与者。 本研究的目的是通过确定一种治疗精神分裂症谱系障碍的方法， 可扩展的方法来优化和个性化治疗。通过促进更好地理解EAP， 神经行为标志物、作为变化机制的早期听觉处理和必要的CR治疗 EAP受损CR参与者的目标，拟议的4年研究将为改善临床决策提供信息- 对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.