Vincent Kathleen F, Zhang Edlyn R, Kato Risako, Cho Angel, Moody Olivia A, Solt Ken
Anesthesia, Critical Care, and Pain Medicine, Massachusetts's General Hospital, Boston, MA, United States.
Harvard Medical School, Boston, MA, United States.
Front Syst Neurosci. 2021 Nov 18;15:762096. doi: 10.3389/fnsys.2021.762096. eCollection 2021.
As the number of individuals undergoing general anesthesia rises globally, it becomes increasingly important to understand how consciousness and cognition are restored after anesthesia. In rodents, levels of consciousness are traditionally captured by physiological responses such as the return of righting reflex (RORR). However, tracking the recovery of cognitive function is comparatively difficult. Here we use an operant conditioning task, the 5-choice serial reaction time task (5-CSRTT), to measure sustained attention, working memory, and inhibitory control in male and female rats as they recover from the effects of several different clinical anesthetics. In the 5-CSRTT, rats learn to attend to a five-windowed touchscreen for the presentation of a stimulus. Rats are rewarded with food pellets for selecting the correct window within the time limit. During each session we tracked both the proportion of correct (accuracy) and missed (omissions) responses over time. Cognitive recovery trajectories were assessed after isoflurane (2% for 1 h), sevoflurane (3% for 20 min), propofol (10 mg/kg I.V. bolus), ketamine (50 mg/kg I.V. infusion over 10 min), and dexmedetomidine (20 and 35 μg/kg I.V. infusions over 10 min) for up to 3 h following RORR. Rats were classified as having recovered accuracy performance when four of their last five responses were correct, and as having recovered low omission performance when they missed one or fewer of their last five trials. Following isoflurane, sevoflurane, and propofol anesthesia, the majority (63-88%) of rats recovered both accuracy and low omission performance within an hour of RORR. Following ketamine, accuracy performance recovers within 2 h in most (63%) rats, but low omission performance recovers in only a minority (32%) of rats within 3 h. Finally, following either high or low doses of dexmedetomidine, few rats (25-32%) recover accuracy performance, and even fewer (0-13%) recover low omission performance within 3 h. Regardless of the anesthetic, RORR latency is not correlated with 5-CSRTT performance, which suggests that recovery of neurocognitive function cannot be inferred from changes in levels of consciousness. These results demonstrate how operant conditioning tasks can be used to assess real-time recovery of neurocognitive function following different anesthetic regimens.
随着全球接受全身麻醉的人数不断增加，了解麻醉后意识和认知如何恢复变得越来越重要。在啮齿动物中，意识水平传统上通过诸如翻正反射恢复（RORR）等生理反应来捕捉。然而，追踪认知功能的恢复相对困难。在这里，我们使用一种操作性条件反射任务，即五选择连续反应时间任务（5-CSRTT），来测量雄性和雌性大鼠从几种不同临床麻醉剂的影响中恢复时的持续注意力、工作记忆和抑制控制。在5-CSRTT中，大鼠学会关注一个有五个窗口的触摸屏以等待刺激呈现。大鼠在时间限制内选择正确窗口可获得食物颗粒奖励。在每个实验过程中，我们追踪随着时间推移正确（准确率）和遗漏（错误）反应的比例。在异氟烷（2%，持续1小时）、七氟烷（3%，持续20分钟）、丙泊酚（10毫克/千克静脉推注）、氯胺酮（50毫克/千克静脉输注10分钟）和右美托咪定（20和35微克/千克静脉输注10分钟）麻醉后，在RORR后长达3小时内评估认知恢复轨迹。当大鼠最后五次反应中有四次正确时，被分类为恢复了准确率表现；当它们最后五次试验中遗漏一次或更少时，被分类为恢复了低遗漏表现。在异氟烷、七氟烷和丙泊酚麻醉后，大多数（63 - 88%）大鼠在RORR后一小时内恢复了准确率和低遗漏表现。在氯胺酮麻醉后，大多数（63%）大鼠在2小时内恢复了准确率表现，但在3小时内只有少数（32%）大鼠恢复了低遗漏表现。最后，在高剂量或低剂量右美托咪定麻醉后，很少有大鼠（25 - 32%）在3小时内恢复准确率表现，甚至更少（0 - 13%）大鼠在3小时内恢复低遗漏表现。无论使用何种麻醉剂，RORR潜伏期与5-CSRTT表现均无相关性，这表明神经认知功能的恢复不能从意识水平的变化中推断出来。这些结果证明了操作性条件反射任务可用于评估不同麻醉方案后神经认知功能的实时恢复情况。
