UC Berkeley

Working memory (WM) is the ability to hold information for online processing. As the basis of long-term memory formation and a fundamental construct of thinking, it is paramount that we understand how WM works. Distributed network models posit that the prefrontal cortex (PFC) supports WM by coordinating top-down control over other regions involved in sensory representation and long-term memory. We utilized an episodic memory paradigm that probes WM for identity, spatial, and temporal information to examine the PFC dependent model of WM. In two studies, multimodal electrophysiology data reveal that PFC control over WM is fundamentally dynamic in nature, and that WM is dependent on activity distributed across anterior and posterior cortical regions. Results challenge the simple PFC model of WM.

Ch. 1 presents evidence from intracranial recordings that frontal and medial temporal lobe (MTL) theta rhythms carry WM-related activity, and uncovers two WM systems. The PFC-MTL system exhibits bidirectional interaction that shifts with msec precision in response to task demands. In contrast, MTL rhythms direct activity in the orbitofrontal cortex via theta rhythms that do not vary with task demands. These findings support a bidirectional PFC-MTL system in humans – in which theta rhythms subserve executive control during episodic memory formation. Ch. 2 presents evidence from patients with unilateral PFC damage, which shows that a posteriorly-sourced alpha-beta network provides adequate resources for well above-chance WM accuracy. However, when the PFC is intact, PFC low theta activity increases commensurate with executive demand, and PFC-sourced slow rhythms and posteriorly-sourced alpha-beta rhythms travel in opposite directions to support optimal WM.

Ch. 3 reviews 15 years of intracranial research on human memory, and considers the potential of intracranial electrophysiology as a technique to address unresolved questions in the neuroscience of human memory. Ch. 4 presents key themes from this work for younger readers; specifically, it introduces the concepts of cross-frequency coupling between theta rhythms and fast activities in the MTL, and inter-regional PFC-MTL synchrony for memory formation. In a second public outreach piece, appendix 1 introduces the logic of neuropsychology to younger readers to understand why memories of music are resilient to the deleterious effects of amnesia and dementia. Appendix 2 shows that WM develops in children along with increases in sustained attention, and appendix 3 reviews evidence that executive control develops commensurate with PFC connectivity across distributed neural networks. Finally, appendices 4-5 present applications of research on WM and control, together delineating behavioral and neural underpinnings of optimal relational reasoning in neurologically healthy adults.