Background

The ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis.

Methods

24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules.

Results

Previous work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding.

Conclusions

These findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

中文翻译：

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临床上患有精神病高风险的青少年在规则学习过程中表现出质的改变激活模式。

背景

灵活地将规则应用于新情况的能力是适应性人类行为的关键方面。虽然已知执行功能缺陷会在精神病发作的早期出现，但尚不清楚哪些特定方面受到影响。识别规则学习在精神病的早期阶段是否会受到影响，这对于真正了解精神病的病因是必要的，并且对于设计新颖的治疗方法可能至关重要。因此，我们研究了健康青少年和符合精神病临床高风险（CHR）标准的青少年的规则学习。

方法

24名对照组和22名CHR青少年在执行范例时经历了快速，高分辨率的功能磁共振成像，这要求他们应用新颖的或实践的任务规则。

结果

先前的工作表明，实践规则在任务编码过程中依赖于后外侧前额叶皮层（RLPFC），在任务执行过程中依赖于背外侧前额叶皮层（DLPFC），而新颖的规则则表现出相反的模式。我们未能重复这一发现，在执行过程中对新规则进行了更多的活动。比较HC和CHR组，没有统计学上的显着效果，但是效果大小分析发现，CHR组在编码过程中显示较少的激活，而在演奏过程中显示较大的激活。这表明，CHR组可能在执行任务时使用效率较低的反应性控制来检索任务规则，而不是在规则编码期间主动进行。

结论

这些发现表明，在临床高风险状态下灵活性发生了质的改变，但是，需要更多的数据来确定这些缺陷是否可以预测疾病的进展。