How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL–PFC interactions underlie working memory for everyday experiences.

Summary The ability to represent and select information in working memory provides the neurobiological infrastructure for human cognition. For 80 years, dominant views of working memory have focused on the key role of prefrontal cortex (PFC) [1–8]. However, more recent work has implicated posterior cortical regions [9–12], suggesting that PFC engagement during working memory is dependent on the degree of executive demand. We provide evidence from neurological patients with discrete PFC damage that challenges the dominant models attributing working memory to PFC-dependent systems. We show that neural oscillations, which provide a mechanism for PFC to communicate with posterior cortical regions [13], independently subserve communications both to and from PFC – uncovering parallel oscillatory mechanisms for working memory. Fourteen PFC patients and 20 healthy, age-matched controls performed a working memory task where they encoded, maintained, and actively processed information about pairs of common shapes. In controls, the electroencephalogram (EEG) exhibited oscillatory activity in the low-theta range over PFC and directional connectivity from PFC to parieto-occipital regions commensurate with executive processing demands. Concurrent alpha-beta oscillations were observed over parieto-occipital regions, with directional connectivity from parieto-occipital regions to PFC, regardless of processing demands. Accuracy, PFC low-theta activity, and PFC ➔ parieto-occipital connectivity were attenuated in patients, revealing a PFC-independent, alpha-beta system. The PFC patients still demonstrated task proficiency, which indicates that the posterior alpha-beta system provides sufficient resources for working memory. Taken together, our findings reveal neurologically dissociable PFC and parieto-occipital systems, and suggest that parallel, bidirectional oscillatory systems form the basis of working memory.