PRECHRON · The PREfrontal CHRONometer for Organizing Working Memory

Working memory (WM) is a crucial part of human cognition, yet how the brain maintains and organizes different pieces of information is unresolved. I propose that spike-field coupling (SFC), which is the exact moment in time when a neuron spikes in relation to the surrounding neural oscillation (field), is what organizes WM content. Accordingly, different WM items or features are maintained through SFC at different phases of prefrontal brain oscillations. Metaphorically, the prefrontal oscillation represents a chest, where each phase is a drawer. Neural spiking opens the drawer, allowing specific data to be maintained separately from other data. While this idea is supported by animal research, due to the invasive nature of used methods, evidence in humans is missing. Novel technology, which combines non-invasive neuromodulation (TMS) and physiological recordings (EEG) in a closed-loop system, now enables phase-specific SFC to be non-invasively induced in humans.By leveraging and further developing closed-loop TMS-EEG, PRECHRON will test the idea that the interaction between spiking and oscillation in the prefrontal cortex is the mechanism for separating maintained WM information. Based on previous studies, the focus will be on theta (4-7 Hz) oscillations. PRECHRON will test four independent, non-mutually-exclusive hypotheses: 1. SFC at a resting state (no task) predicts overall WM performance; 2. Phase-specific SFC during a WM task organizes WM of different domains (e.g., verbal and spatial); 3. Phase-specific SFC during a sequential WM task organizes the temporal order of WM items; 4. Phase-specific SFC during a visuospatial WM task organizes the location of WM items. Thus, PRECHRON will explore, for the first time, exactly how the prefrontal cortex maintains various types of WM information. The results will enhance our knowledge of neurophysiological processes in human cognition and open the door to understanding cognitive deficits in brain-related disorders.