Robble Mykel A, Schroder Hans S, Kangas Brian D, Nickels Stefanie, Breiger Micah, Iturra-Mena Ann M, Perlo Sarah, Cardenas Emilia, Der-Avakian Andre, Barnes Samuel A, Leutgeb Stefan, Risbrough Victoria B, Vitaliano Gordana, Bergman Jack, Carlezon William A, Pizzagalli Diego A
McLean Hospital & Harvard Medical School, Belmont, MA, USA.
University of Michigan Medical School, Ann Arbor, MI, USA.
Neuropsychopharmacology. 2021 Jun;46(7):1252-1262. doi: 10.1038/s41386-021-00998-4. Epub 2021 Mar 21.
Progress towards understanding neural mechanisms in humans relevant to psychiatric conditions has been hindered by a lack of translationally-relevant cognitive tasks for laboratory animals. Accordingly, there is a critical need to develop parallel neurophysiological assessments of domains of cognition, such as cognitive control, in humans and laboratory animals. To address this, we developed a touchscreen-based cognitive (Eriksen Flanker) task in rats and used its key characteristics to construct a novel human version, with similar testing parameters and endpoints across species. We obtained continuous electroencephalogram (EEG) recordings, including local field potentials in rats, and compared electrophysiological signatures locked to stimulus onset and responses across species. We also assessed whether behavioral or physiological task effects were modulated by modafinil, which enhances aspects of cognitive function in humans. In both species, the task elicited expected flanker interference effects (reduced accuracy) during high-conflict trials. Across homologous neuroanatomical loci, stimulus-locked increases in theta power during high-conflict trials as well as error-related negative potentials were observed. These endpoints were not affected by modafinil in either species. Despite some species-specific patterns, our findings demonstrate the feasibility of a rat Flanker task as well as cross-species behavioral and neurophysiological similarities, which may enable novel insights into the neural correlates of healthy and aberrant behavior and provide mechanistic insights relevant to treatment.
由于缺乏适用于实验动物的与转化相关的认知任务，在理解与精神疾病相关的人类神经机制方面的进展受到了阻碍。因此，迫切需要开发针对人类和实验动物认知领域（如认知控制）的平行神经生理学评估方法。为了解决这个问题，我们在大鼠中开发了一种基于触摸屏的认知（埃里克森侧翼）任务，并利用其关键特征构建了一个新颖的人类版本，跨物种具有相似的测试参数和终点。我们获得了连续脑电图（EEG）记录，包括大鼠的局部场电位，并比较了跨物种与刺激开始和反应相关的电生理特征。我们还评估了行为或生理任务效应是否受到莫达非尼的调节，莫达非尼可增强人类认知功能的各个方面。在两个物种中，该任务在高冲突试验期间引发了预期的侧翼干扰效应（准确性降低）。在同源神经解剖位点上，在高冲突试验期间观察到刺激锁定的θ功率增加以及错误相关负电位。这些终点在两个物种中均未受到莫达非尼的影响。尽管存在一些物种特异性模式，但我们的研究结果证明了大鼠侧翼任务的可行性以及跨物种行为和神经生理学的相似性，这可能有助于对健康和异常行为的神经相关性获得新的见解，并提供与治疗相关的机制性见解。
