Ventromedial Prefrontal Cortex Drives the Prioritization of Self-Associated Stimuli in Working Memory

Humans show a pervasive bias for processing self- over other-related information, including in working memory (WM), where people prioritize the maintenance of self- (over other-) associated cues. To elucidate the neural mechanisms underlying this self-bias, we paired a self- versus other-associated spatial WM task with fMRI and transcranial direct current stimulation (tDCS) of human participants of both sexes. Maintaining self- (over other-) associated cues resulted in enhanced activity in classic WM regions (frontoparietal cortex), and in superior multivoxel pattern decoding of the cue locations from visual cortex. Moreover, ventromedial PFC (VMPFC) displayed enhanced functional connectivity with WM regions during maintenance of self-associated cues, which predicted individuals'' behavioral self-prioritization effects. In a follow-up tDCS experiment, we targeted VMPFC with excitatory (anodal), inhibitory (cathodal), or sham tDCS. Cathodal tDCS eliminated the self-prioritization effect. These findings provide strong converging evidence for a causal role of VMPFC in driving self-prioritization effects in WM and provide a unique window into the interaction between social, self-referential processing and high-level cognitive control processes.SIGNIFICANCE STATEMENT People have a strong tendency to attend to self-related stimuli, such as their names. This self-bias extends to the automatic prioritization of arbitrarily self-associated stimuli held in working memory. Since working memory is central to high-level cognition, this bias could influence how we make decisions. It is therefore important to understand the underlying brain mechanisms. Here, we used neuroimaging and noninvasive neurostimulation techniques to show that the source of self-bias in working memory is the ventromedial PFC, which modulates activity in frontoparietal brain regions to produce prioritized representations of self-associated stimuli in sensory cortex. This work thus reveals a brain circuit underlying the socially motivated (self-referential) biasing of high-level cognitive processing.