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

Abstract

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.

Figure 1

Default Mode and Ventral Somatomotor Resting-State Networks (A) Group-level fixed-effects image of default mode network (DMN; left) and ventral somatomotor network (VSN; right) in two rhesus monkeys. Networks are shown at slices most representative of the correlation pattern on which network identification was based. Images were statistically thresholded at Z > 2 and overlaid on a composite structural from the UWRMAC-DTI271 atlas space. See Figure S1 for other resting-state independent components (ICs) present in both monkeys. (B) DMN time course for a representative 10 min session in monkey 1 (top plot) and monkey 2 (bottom plot), where red dots below represent the onset of hippocampal ripple events. Representative sessions were chosen based on closeness to mean IC rank out of all present ICs for a given session (monkey 1: mean = 4.04, displayed = 3; monkey 2: mean = 6.64, displayed = 7) and ripple amount (monkey 1: mean = 68.8, displayed = 69; monkey 2: mean = 41.2, displayed = 39).

Figure 2

Influence of Hippocampal Neural Events on DMN and VSN (A) Beta values for each network and neural event for monkey 1 (mean ± SEM). There were significantly higher DMN activations after ripples compared to hpsigma (t(24) = 5.99, p < 0.001) or gamma (t(24) = 2.50, p = 0.020) events. Additionally, there was significantly higher DMN versus VSN activity (t(24) = 3.62, p = 0.001) after ripples. There was also a significant decrease in DMN activity (t(24) = −3.55, p = 0.002) after hpsigma events, also when compared to gamma events (t(24) = −2.45, p = 0.022). DMN activity was also significantly lower (t(24) = −3.05, p = 0.006) compared to VSN activity after hpsigma events. (B) Beta values for each network and neural event for monkey 2 (mean ± SEM). There was significantly higher DMN activity after ripples compared to hpsigma (t(21) = 6.48, p < 0.001) or gamma (t(20) = 7.42, p < 0.001) events. Additionally, there was significantly higher DMN versus VSN activity after ripples (t(21) = 11.6, p < 0.001). Converse to monkey 1, there was a significant increase in DMN activity after hpsigma events (t(21) = 3.25, p = 0.004), which was significantly higher (t(20) = 2.26, p = 0.035) than after DMN gamma events and also higher (t(21) = 3.86, p = 0.001) than VSN activity after hpsigma events. There was a significant decrease in ventral somatomotor activity after the onset of ripple events (t(24) = −3.06, p = 0.006). See Figure S2 for mean plots averaged across both monkeys, along with plots showing effect of ripples on other neocortical RSNs.

Figure 3

Time Course of Hippocampal Neural Events in DMN and VSN (A) Evoked response values (signal amplitude presented in arbitrary units) for each network and neural event for monkey 1 starting from 5 TRs (10 s) prior to event onset until 5 TRs after event onset (mean across datasets ± SEM). (B) Evoked response values for each network and neural event for monkey 2. See Figure S3 for time courses averaged across both monkeys.