Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network

The default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1-3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4, 5]-particularly in DMN regions [6-8]. Mechanistic support for the DMN's role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples-both during sleep [9, 10] and awake deliberative periods [11-13]. Ripples are ideally suited for memory consolidation [14, 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16-19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20-22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24-26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs-like the DMN-unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics.