Cognitive flexibility is a prefrontal cortex-dependent neurocognitive process that enables behavioral adaptation in response to changes in environmental contingencies. Electrical vagus nerve stimulation (VNS) enhances several forms of learning and neuroplasticity, but its effects on cognitive flexibility have not been evaluated. In the current study, a within-subjects design was used to assess the effects of VNS on performance in a novel visual discrimination reversal learning task conducted in touchscreen operant chambers. The task design enabled simultaneous assessment of acute VNS both on reversal learning and on recall of a well-learned discrimination problem. Acute VNS delivered in conjunction with stimuli presentation during reversal learning reliably enhanced learning of new reward contingencies. Enhancement was not observed, however, if VNS was delivered during the session but was not coincident with presentation of to-be-learned stimuli. In addition, whereas VNS delivered at 30 HZ enhanced performance, the same enhancement was not observed using 10 or 50 Hz. Together, these data show that acute VNS facilitates reversal learning and indicate that the timing and frequency of the VNS are critical for these enhancing effects. In separate rats, administration of the norepinephrine reuptake inhibitor atomoxetine also enhanced reversal learning in the same task, consistent with a noradrenergic mechanism through which VNS enhances cognitive flexibility.

认知灵活性是一种依赖于前额皮质的神经认知过程，能够根据环境突发事件的变化进行行为适应。迷走神经电刺激（VNS）可增强多种形式的学习和神经可塑性，但其对认知灵活性的影响尚未得到评估。在当前的研究中，采用受试者内设计来评估 VNS 对在触摸屏操作室中进行的新型视觉辨别逆转学习任务表现的影响。该任务设计能够同时评估急性 VNS 的逆向学习和对熟悉的辨别问题的回忆。急性 VNS 与逆向学习期间的刺激呈现相结合，可靠地增强了对新奖励意外事件的学习。然而，没有观察到增强，如果 VNS 在课程期间进行，但与要学习的刺激的呈现不一致。此外，虽然 VNS 在 30 Hz 下提供了增强的性能，但使用 10 或 50 Hz 时并未观察到相同的增强。总之，这些数据表明，急性 VNS 促进逆转学习，并表明 VNS 的时间和频率对于这些增强效果至关重要。在单独的大鼠中，给予去甲肾上腺素再摄取抑制剂阿托莫西汀也增强了同一任务中的逆转学习，这与 VNS 增强认知灵活性的去甲肾上腺素能机制一致。这些数据表明，急性 VNS 有助于逆转学习，并表明 VNS 的时间和频率对于这些增强效果至关重要。在单独的大鼠中，给予去甲肾上腺素再摄取抑制剂阿托莫西汀也增强了同一任务中的逆转学习，这与 VNS 增强认知灵活性的去甲肾上腺素能机制一致。这些数据表明，急性 VNS 有助于逆转学习，并表明 VNS 的时间和频率对于这些增强效果至关重要。在单独的大鼠中，给予去甲肾上腺素再摄取抑制剂阿托莫西汀也增强了同一任务中的逆转学习，这与 VNS 增强认知灵活性的去甲肾上腺素能机制一致。