Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States; Research Service MIRECC, VISN 22, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, United States.
J Neurosci Methods. 2017 Dec 1;292:53-60. doi: 10.1016/j.jneumeth.2017.07.011. Epub 2017 Jul 25.
Neurodevelopmental disorders including Tourette's syndrome (TS) and attention deficit hyperactivity disorder (ADHD) are characterized by significant impairment in attention and cognitive control. These cognitive deficits persist throughout development, contribute significantly to socio-occupational impairment, and are relatively impervious to available treatment. A critical challenge in pro-cognitive drug discovery is translatability of findings across species, underscoring the need for developing valid and reliable cross-species cognitive tasks.
Here we describe a cross-species 5 choice continuous performance task that was developed to measure cognitive control processes of attention, vigilance, and response inhibition, enabling the translation of findings for pro-cognitive drug discovery across species and delineate neural mechanisms underlying cognitive control construct.
Construct validity of 5C-CPT has been verified by multiple cross-species studies. Several lines of evidence report consistent findings across species including, deficits resulting from 36-h sleep deprivation studies, engagement of parietal cortex in human brain imaging and rodent lesion studies, and vigilance decrements over time.
Unlike the widely used rodent 5 choice serial reaction time task (5CSRTT) and the sustained attention task (SAT), the rodent 5C-CPT includes both target and non-target stimuli that allow measuring of cognitive control elements including response inhibition, an ability to inhibit pre-potent response during non-target trials, detect vigilance decrement and calculate signal detection parameters in rodents analogous to human CPT.
The cross-species 5C-CPT is a robust translational tool to characterize the neurobiological substrates underlying cognitive control deficits in clinical population including, ADHD and TS and develop targeted pro-cognitive therapeutics.
神经发育障碍包括妥瑞氏症（TS）和注意缺陷多动障碍（ADHD），其特征是注意力和认知控制方面存在严重障碍。这些认知缺陷在整个发育过程中持续存在，对社会职业障碍有重大影响，并且相对不受现有治疗方法的影响。在促进认知药物发现方面的一个关键挑战是跨物种发现的可转化性，这突出了开发有效和可靠的跨物种认知任务的必要性。
本文描述了一种跨物种的 5 选择连续绩效任务，旨在测量注意力、警觉性和反应抑制的认知控制过程，使跨物种的促认知药物发现发现能够转化，并阐明认知控制结构的神经机制。
5C-CPT 的结构有效性已通过多项跨物种研究得到验证。有几行证据报告了跨物种的一致发现，包括 36 小时睡眠剥夺研究、人类大脑成像和啮齿动物损伤研究中的顶叶皮层参与以及随着时间的推移警觉性下降。
与广泛使用的啮齿动物 5 选择序列反应时间任务（5CSRTT）和持续性注意任务（SAT）不同，啮齿动物 5C-CPT 包括目标和非目标刺激，允许测量认知控制元素，包括反应抑制，即在非目标试验期间抑制预先存在的反应的能力，在啮齿动物中检测警觉性下降并计算类似于人类 CPT 的信号检测参数。
跨物种的 5C-CPT 是一种强大的转化工具，可用于描述包括 ADHD 和 TS 在内的临床人群中认知控制缺陷的神经生物学基础，并开发针对认知的治疗方法。
