RT Journal Article SR Electronic T1 Working memory updating in the macaque lateral prefrontal cortex JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP e1770242024 DO 10.1523/JNEUROSCI.1770-24.2024 A1 Qian, Yichen A1 Herikstad, Roger A1 Libedinsky, Camilo YR 2024 UL http://www.jneurosci.org/content/early/2024/12/08/JNEUROSCI.1770-24.2024.abstract AB Working memory updating is an important executive process. Here, we study the single-neuron mechanisms involved in updating versus protecting memory from distractors in the macaque prefrontal cortex. We recorded single-neuron activity from the lateral prefrontal cortex (LPFC) and prearcuate cortex (PAC) while male monkeys performed a task that required them to update their memory of target locations while ignoring distractors. Our findings revealed that neurons in the PAC signaled updated memory locations approximately ∼100 ms after stimulus onset, significantly faster than the ∼400 ms observed in the LPFC. Additionally, PAC neurons exhibited longer encoding of distractor information. Population decoding analyses further indicated that distractor information was maintained in orthogonal subspaces from target information in both regions, minimizing interference. These results demonstrate the distinct temporal dynamics in memory updating processes between the PAC and LPFC and highlight the interplay between robust memory maintenance and updating, suggesting that local neural mechanisms may contribute to these processes.Significance Statement Working memory is a fundamental cognitive function. It stored information in the short term, and this information can be manipulated to allow intelligent behaviors. The lateral prefrontal cortex is involved in this process, but the mechanisms of working memory manipulation remain unclear. Here, we studied one type of manipulation; working memory updating, which refers to the exchange of one memory for another. We found that two adjacent regions in the lateral prefrontal cortex show different updating times: while a posterior region updates memory content very fast, the more anterior region takes significantly longer. These results show that working memory updating may involve multiple operations, such as updating of memory or attention versus updating of motor plans.