Abstract：
BACKGROUND: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future.
METHODS: The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants.
RESULTS: Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132).
CONCLUSIONS: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.
METHODS: The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study-identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants.
RESULTS: Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132).
CONCLUSIONS: This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.
摘要：
背景：神经认知障碍是精神分裂症中众所周知的现象，在精神病发作之前就开始了。连接组范围的关联研究将认知表现与静息状态fMRI联系不一致。我们假设精心选择的认知工具和完善的人群将允许通过连接组范围的关联研究来识别可靠的大脑行为关联。为了检验这个假设，我们首先通过一项关于早期精神病的全连接组的关联研究确定了大脑认知的相关性.然后我们问，在一个独立的数据集中，如果这些大脑-认知关系将推广到未来发展为精神病的个体。
方法：Seidman听觉持续绩效任务（ACPT）有效地将健康参与者与精神病患者区分开来。我们的全连接体关联研究使用人类连接体早期精神病项目（n=183）来确定连接与ACPT性能之间的联系。然后，我们分析了北美前驱体纵向研究2(n=345)，一项针对有精神病风险的个体的多站点前瞻性研究。我们在有精神病风险的个体和对照组中测试了连接组范围的关联研究确定的认知-连接关系。
结果：我们在早期精神病中的全连接组关联研究发现，ACPT表现较好和前额叶-躯体运动连接较高之间存在密切关联（p<.005）。前额叶-躯体运动连接也与可能发展为精神病的高危个体的ACPT表现有关（n=17）。在非转换器（n=196）或对照（n=132）中未观察到这一发现。
结论：这项连接组范围的关联研究确定了不同的精神病样本和以后会发展为精神病的高危个体的连通性和认知之间的可重复联系。精心选择的任务和人群可以提高连接组范围的关联研究识别可靠的脑表型关系的能力。
方法：Seidman听觉持续绩效任务（ACPT）有效地将健康参与者与精神病患者区分开来。我们的全连接体关联研究使用人类连接体早期精神病项目（n=183）来确定连接与ACPT性能之间的联系。然后，我们分析了北美前驱体纵向研究2(n=345)，一项针对有精神病风险的个体的多站点前瞻性研究。我们在有精神病风险的个体和对照组中测试了连接组范围的关联研究确定的认知-连接关系。
结果：我们在早期精神病中的全连接组关联研究发现，ACPT表现较好和前额叶-躯体运动连接较高之间存在密切关联（p<.005）。前额叶-躯体运动连接也与可能发展为精神病的高危个体的ACPT表现有关（n=17）。在非转换器（n=196）或对照（n=132）中未观察到这一发现。
结论：这项连接组范围的关联研究确定了不同的精神病样本和以后会发展为精神病的高危个体的连通性和认知之间的可重复联系。精心选择的任务和人群可以提高连接组范围的关联研究识别可靠的脑表型关系的能力。
