Richter S Helene, Vogel Anne S, Ueltzhöffer Kai, Muzzillo Chiara, Vogt Miriam A, Lankisch Katja, Armbruster-Genç Diana J N, Riva Marco A, Fiebach Christian J, Gass Peter, Vollmayr Barbara
Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany ; Bernstein Center for Computational Neuroscience Heidelberg/Mannheim, Germany.
Bernstein Center for Computational Neuroscience Heidelberg/Mannheim, Germany ; Department of Psychology, Goethe University Frankfurt am Main, Germany.
Front Behav Neurosci. 2014 May 5;8:154. doi: 10.3389/fnbeh.2014.00154. eCollection 2014.
The abilities to either flexibly adjust behavior according to changing demands (cognitive flexibility) or to maintain it in the face of potential distractors (cognitive stability) are critical for adaptive behavior in many situations. Recently, a novel human paradigm has found individual differences of cognitive flexibility and stability to be related to common prefrontal networks. The aims of the present study were, first, to translate this paradigm from humans to mice and, second, to test conceptual predictions of a computational model of prefrontal working memory mechanisms, the Dual State Theory, which assumes an antagonistic relation between cognitive flexibility and stability. Mice were trained in a touchscreen-paradigm to discriminate visual cues. The task involved "ongoing" and cued "switch" trials. In addition distractor cues were interspersed to test the ability to resist distraction, and an ambiguous condition assessed the spontaneous switching between two possible responses without explicit cues. While response times did not differ substantially between conditions, error rates (ER) increased from the "ongoing" baseline condition to the most complex condition, where subjects were required to switch between two responses in the presence of a distracting cue. Importantly, subjects switching more often spontaneously were found to be more distractible by task irrelevant cues, but also more flexible in situations, where switching was required. These results support a dichotomy of cognitive flexibility and stability as predicted by the Dual State Theory. Furthermore, they replicate critical aspects of the human paradigm, which indicates the translational potential of the testing procedure and supports the use of touchscreen procedures in preclinical animal research.
根据不断变化的需求灵活调整行为（认知灵活性）或在面对潜在干扰因素时保持行为（认知稳定性）的能力，在许多情况下对于适应性行为至关重要。最近，一种新的人类范式发现认知灵活性和稳定性的个体差异与常见的前额叶网络有关。本研究的目的，首先是将这种范式从人类转换到小鼠，其次是测试前额叶工作记忆机制计算模型——双态理论的概念预测，该理论假设认知灵活性和稳定性之间存在拮抗关系。小鼠在触摸屏范式中接受训练以区分视觉线索。该任务包括“持续”和提示“切换”试验。此外，干扰线索被穿插其中以测试抵抗干扰的能力，并且一种模糊条件评估了在没有明确线索的情况下两种可能反应之间的自发切换。虽然不同条件下的反应时间没有显著差异，但错误率从“持续”基线条件增加到最复杂的条件，即在存在干扰线索的情况下受试者需要在两种反应之间切换。重要的是，发现自发切换更频繁的受试者更容易受到与任务无关线索的干扰，但在需要切换的情况下也更灵活。这些结果支持了双态理论所预测的认知灵活性和稳定性的二分法。此外，它们复制了人类范式的关键方面，这表明了测试程序的转化潜力，并支持在临床前动物研究中使用触摸屏程序。
