Department of Integrative Physiology, Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Brain Science Institute, Tamagawa University, 6-1-1 Tamagawagakuen, Machida, Tokyo, 194-8610, Japan.
Commun Biol. 2022 Jul 20;5(1):690. doi: 10.1038/s42003-022-03626-z.
Flexible decision making is an indispensable ability for humans. A subanesthetic dose of ketamine, an N-methyl-D-aspartate receptor antagonist, impairs this flexibility in a manner that is similar to patients with schizophrenia; however how it affects neural processes related to decision making remains unclear. Here, we report that ketamine administration impairs neural processing related to context-dependent decision making, and delays the onset of decision making. We recorded single unit activity in the lateral intraparietal area (LIP) while monkeys switched between a direction-discrimination task and a depth-discrimination task. Ketamine impaired choice accuracy for incongruent stimuli that required different decisions depending on the task, for the direction-discrimination task. Neural sensitivity to irrelevant depth information increased with ketamine during direction discrimination in LIP, indicating impaired processing of irrelevant information. Furthermore, the onset of decision-related neural activity was delayed in conjunction with an increased reaction time irrespective of task and stimulus congruency. Neural sensitivity and response onset of the middle temporal area (MT) were not modulated by ketamine, indicating that ketamine worked on neural decision processes downstream of MT. These results suggest that ketamine administration may impair what information to process and when to process it for the purpose of achieving flexible decision making.
灵活决策是人类不可或缺的能力。亚麻醉剂量的氯胺酮是一种 N-甲基-D-天冬氨酸受体拮抗剂，它以类似于精神分裂症患者的方式损害这种灵活性；然而，它如何影响与决策相关的神经过程仍不清楚。在这里，我们报告氯胺酮给药会损害与上下文相关的决策相关的神经处理，并延迟决策的开始。我们在猴子在方向辨别任务和深度辨别任务之间切换时，记录了外侧顶内区（LIP）的单个单位活动。氯胺酮损害了需要根据任务做出不同决策的不一致刺激的选择准确性，对于方向辨别任务。在 LIP 进行方向辨别时，氯胺酮会增加对无关深度信息的神经敏感性，表明对无关信息的处理受损。此外，与反应时间增加相关，与任务和刺激一致性无关，决策相关神经活动的开始被延迟。中颞区（MT）的神经敏感性和反应开始不受氯胺酮的调节，表明氯胺酮作用于 MT 下游的神经决策过程。这些结果表明，氯胺酮给药可能会损害为了实现灵活决策而处理哪些信息以及何时处理这些信息。
