Time-on-task-related decrements in performance in the rodent continuous performance test are not caused by physical disengagement from the task.

NPP-digital psychiatry and neuroscience Pub Date : 2025-01-01 Epub Date: 2025-02-13 DOI:10.1038/s44277-025-00025-0
Ye Li, Thomas van Kralingen, Megan Masi, Brandon Villanueva Sanchez, Beyonca Mitchell, Joshua Johnson, Jorge Miranda-Barrientos, Jason Rehg, Keri Martinowich, Gregory V Carr
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Abstract

Attention deficits, a hallmark of many neuropsychiatric disorders, significantly impair quality of life and functional outcome for patients. Continuous Performance Tests (CPTs) are widely used to assess attentional function in clinical settings and have been adapted for mice as the rodent Continuous Performance Test (rCPT). In this study, we combined traditional analyses of rCPT performance with markerless pose estimation using DeepLabCut and visual field analysis (VFA) to objectively measure the orientation of mice toward stimuli during rCPT sessions. Additionally, we extended the session length to assess performance decrements over time. Our findings show that extending rCPT sessions from 45-90 min results in a significant decline in performance in male mice, which aligns with performance decrements observed in clinical research. Importantly, physical engagement with the task remained relatively stable throughout the session, even as performance deteriorated. This suggests that the performance decline specifically reflects a time-on-task (TOT)-dependent vigilance decrement rather than physical disengagement. We also investigated the effects of amphetamine, an FDA-approved treatment for attention-deficit/hyperactivity disorder (ADHD), on rCPT performance. Amphetamine significantly reduced false alarms without affecting orientation or physical engagement with task stimuli in both male and female mice. This improved rCPT performance in males, but not in females because hit rate also declined following amphetamine administration in females. Collectively, these findings validate a behavioral tracking platform for objectively measuring physical engagement in the rCPT and a task modification that accentuates TOT-dependent performance decrements, enhancing the translational value of the rCPT for studies related to human neuropsychiatric disorders.

在啮齿动物连续表现测试中,与任务时间相关的表现下降不是由身体脱离任务引起的。
注意缺陷是许多神经精神疾病的标志,严重损害患者的生活质量和功能预后。连续表现测试(CPTs)在临床环境中被广泛用于评估注意力功能,并已被改编为啮齿类动物连续表现测试(rCPT)。在这项研究中,我们将传统的rCPT表现分析与使用DeepLabCut和视野分析(VFA)的无标记姿态估计相结合,客观地测量了小鼠在rCPT过程中对刺激的方向。此外,我们延长了会话长度,以评估性能随时间的下降。我们的研究结果表明,将rCPT时间从45-90分钟延长会导致雄性小鼠的表现显著下降,这与临床研究中观察到的表现下降一致。重要的是,在整个过程中,即使表现恶化,对任务的身体参与仍然相对稳定。这表明,表现下降具体反映了任务时间(TOT)依赖性警觉性下降,而不是身体脱离。我们还研究了安非他明对rCPT表现的影响,安非他明是一种fda批准的治疗注意力缺陷/多动障碍(ADHD)的药物。安非他明在不影响雄性和雌性小鼠对任务刺激的定向或身体参与的情况下显著减少了假警报。这改善了男性的rCPT表现,但没有改善女性的rCPT表现,因为女性服用安非他明后命中率也有所下降。总的来说,这些发现验证了一个行为跟踪平台,可以客观地测量rCPT中的身体参与程度,以及一个任务修改,强调了tot依赖性的表现下降,增强了rCPT在人类神经精神疾病相关研究中的转化价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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