Lateral prefrontal cortex controls interplay between working memory and actions

Humans must often keep multiple task goals in mind, at different levels of priority and immediacy, while also interacting with the environment. We might need to remember information for an upcoming task while engaged in more immediate actions. Consequently, actively maintained working memory (WM) content may bleed into ongoing but unrelated motor behavior. Here, we experimentally test the impact of WM maintenance on action execution, and we transcranially stimulate lateral prefrontal cortex (PFC) to parse its functional contributions to WM-motor interactions. We first created a task scenario wherein human participants (both sexes) executed cued hand movements during WM maintenance. We manipulated the compatibility between WM and movement goals at the trial level and the statistical likelihood that the two would be compatible at the block level. We found that remembering directional words (e.g., left, down) biased the trajectory and speed of hand movements that occurred during the WM delay, but the bias was dampened in blocks when WM content predictably conflicted with movement goals. Then we targeted left lateral PFC with two different transcranial magnetic stimulation (TMS) protocols before participants completed the task. We found that an intermittent theta-burst protocol, which is thought to be excitatory, dampened sensitivity to block-level control demands (i.e., proactive control), while a continuous theta-burst protocol, which is thought to be inhibitory, dampened adaptation to trial-by- trial conflict (i.e., reactive control). Therefore, lateral PFC is involved in controlling the interplay between WM content and manual action, but different PFC mechanisms may support different time-scales of adaptive control. Significance StatementWorking memory (WM) allows us to keep information active in mind to achieve our moment-to-moment goals. However, WM maintenance may sometimes unintentionally shape our externally-geared actions. This study formalizes the everyday "action slips" humans commit when we type out or say the wrong word in conversation because it was held in mind for a different goal. The results show that internally maintained content can influence ongoing hand movements, but this interplay between WM and motor behavior depends on the cortical excitability state of the lateral PFC. Neural perturbation with transcranial magnetic stimulation (TMS) shows that temporarily increasing or decreasing PFC excitability can make participants more or less susceptible to the impact of WM on actions.