Layer-dependent activity in human prefrontal cortex during working memory

Working memory involves storing and/or manipulating previously encoded information over a short-term delay period, which is typically followed by a behavioral response based on the remembered information. While working memory tasks often engage dorsolateral prefrontal cortex (dlPFC), few studies have investigated whether their sub-processes are localized to different cortical depths in this region, and none have done so in humans. Here, we use high-resolution functional MRI to interrogate the layer specificity of neural activity during different periods of a delayed-response task in dlPFC. We detect activity timecourses that follow the hypothesized patterns: namely, superficial layers are preferentially active during the delay period, and specifically in trials requiring manipulation (rather than mere maintenance) of information held in working memory, while deeper layers are preferentially active during the response. Results demonstrate that layer-specific fMRI can be used in higher-order brain regions to non-invasively map cognitive processing in humans.