Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA.
Sci Rep. 2021 Jun 3;11(1):11665. doi: 10.1038/s41598-021-91091-9.
Challenges in therapeutics development for neuropsychiatric disorders can be attributed, in part, to a paucity of translational models capable of capturing relevant phenotypes across clinical populations and laboratory animals. Touch-sensitive procedures are increasingly used to develop innovative animal models that better align with testing conditions used in human participants. In addition, advances in electrophysiological techniques have identified neurophysiological signatures associated with characteristics of neuropsychiatric illness. The present studies integrated these methodologies by developing a rat flanker task with electrophysiological recordings based on reverse-translated protocols used in human electroencephalogram (EEG) studies of cognitive control. Various touchscreen-based stimuli were evaluated for their ability to efficiently gain stimulus control and advance to flanker test sessions. Optimized stimuli were then examined for their elicitation of prototypical visual evoked potentials (VEPs) across local field potential (LFP) wires and EEG skull screws. Of the stimuli evaluated, purple and green photographic stimuli were associated with efficient training and expected flanker interference effects. Orderly stimulus-locked outcomes were also observed in VEPs across LFP and EEG recordings. These studies along with others verify the feasibility of concurrent electrophysiological recordings and rodent touchscreen-based cognitive testing and encourage future use of this integrated approach in therapeutics development.
神经精神疾病治疗开发面临的挑战部分归因于缺乏能够跨临床人群和实验室动物捕捉相关表型的转化模型。触感程序越来越多地被用于开发与人类参与者中使用的测试条件更一致的创新动物模型。此外，电生理技术的进步已经确定了与神经精神疾病特征相关的神经生理特征。本研究通过开发一种基于反向翻译的人类脑电图（EEG）认知控制研究中使用的协议的大鼠侧翼任务，并结合电生理记录，整合了这些方法。评估了各种基于触摸屏的刺激物，以确定它们是否能够有效地获得刺激控制并进入侧翼测试阶段。然后，优化后的刺激物被检查是否能在局部场电位（LFP）线和 EEG 颅骨螺钉上产生典型的视觉诱发电位（VEP）。在所评估的刺激物中，紫色和绿色摄影刺激物与有效的训练和预期的侧翼干扰效应有关。在 LFP 和 EEG 记录中也观察到有序的刺激锁定结果。这些研究以及其他研究验证了同时进行电生理记录和啮齿动物基于触摸屏的认知测试的可行性，并鼓励在治疗开发中未来使用这种综合方法。
