Causal Contribution of Awake Post-encoding Processes to Episodic Memory Consolidation

• Published in: Current biology 2020-09, Vol.30 (18), p.3533-3543.e7
• Main Authors: Tambini, Arielle, D’Esposito, Mark
• Format: Article
• Language: English
• Subjects: awake rest; causal manipulations; fMRI-TMS; hippocampal-cortical interactions; hippocampus; lateral occipital cortex; memory consolidation; reactivation; resting state; transcranial magnetic stimulation
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.06.063

Stable representations of past experience are thought to depend on processes that unfold after events are initially encoded into memory. Post-encoding reactivation and hippocampal-cortical interactions are leading candidate mechanisms thought to support memory retention and stabilization across hippocampal-cortical networks. Although putative consolidation mechanisms have been observed during sleep and periods of awake rest, the direct causal contribution of awake consolidation mechanisms to later behavior is unclear, especially in humans. Moreover, it has been argued that observations of putative consolidation processes are epiphenomenal and not causally important, yet there are few tools to test the functional contribution of these mechanisms in humans. Here, we combined transcranial magnetic stimulation (TMS) and fMRI to test the role of awake consolidation processes by targeting hippocampal interactions with lateral occipital cortex (LOC). We applied theta-burst TMS to LOC (and a control site) to interfere with an extended window (approximately 30–50 min) after memory encoding. Behaviorally, post-encoding TMS to LOC selectively impaired associative memory retention compared to multiple control conditions. In the control TMS condition, we replicated prior reports of post-encoding reactivation and memory-related hippocampal-LOC interactions during periods of awake rest using fMRI. However, post-encoding LOC TMS reduced these processes, such that post-encoding reactivation in LOC and memory-related hippocampal-LOC functional connectivity were no longer present. By targeting and manipulating post-encoding neural processes, these findings highlight the direct contribution of awake time periods to episodic memory consolidation. This combined TMS-fMRI approach provides an opportunity for causal manipulations of human memory consolidation. [Display omitted] •Post-encoding TMS was applied to manipulate awake memory consolidation in humans•TMS to LOC selectively reduced associative versus item memory retention•TMS impaired cortical memory reactivation and hippocampal-cortical interactions•TMS modified patterns of post-encoding hippocampal interactions related to memory To test the role of awake post-encoding processes in memory consolidation, Tambini and D'Esposito combine post-encoding theta-burst transcranial magnetic stimulation with fMRI. Stimulation to lateral occipital cortex after memory encoding impairs associative memory retention behaviorally and disru