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. Although working memory tasks often engage dorsolateral prefrontal cortex, few studies have investigated whether their subprocesses 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 dorsolateral prefrontal cortex. We detect activity time courses that follow the hypothesized patterns: namely, superficial layers are preferentially active during the delay period, specifically in trials requiring manipulation (rather than mere maintenance) of information held in working memory, and deeper layers are preferentially active during the response. Results demonstrate that layer-specific functional MRI can be used in higher-order brain regions to noninvasively map cognitive processing in humans.