Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.

Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.hippocampus | memory | in vivo electrophysiology | fMRI | local field potential M emory processes require mechanisms for large-scale integration of neuronal activity, in which information processing is precisely coordinated at multiple scales. A prominent example of such phenomenon is the replay of specific sequences of action potentials of hippocampal and neocortical neurons, reflecting previous experiences during wakefulness (1-7). Sharpwave-ripple (SPW-R) complexes observed in the hippocampal CA1 local field potential (LFP) mark the reactivation of these sequences by the simultaneous occurrence of two distinct but related phenomena: a strong LFP deflection, known as sharp wave (SPW), and a high-frequency oscillation known as ripple (8,9). SPW-R episodes are thought to reflect brain-wide processes mediating memory consolidation (10-13). However, the largescale cooperative mechanisms associated to these episodes and their relationship to the observed SPW-R electrical signature remain largely unknown. Investigating this relationship is critical for understanding memory processes at a system level and may provide new insights into the mechanisms of pathological fast ripples observed during epilepsy (14).Although they were initially thought to occur during slow-wave sleep and quiescence periods, later on SPW-R and sequence replay were also observed during or shortly after active behavior (15-17). Moreover, many SPW-Rs occur at path choice points (18,19), which are also locations where vicarious trial and error are reported (20). Thus, reactivation of memory sequences during SPW-Rs could provide a convenient mechanism not only for consolidation of long-term memory (4) but also for quickly recalling memories during awake state, serving various cognitive functions (21). The generation of SPW-R complexes in these various contexts likely involves brain-wide network mechanisms, and as a conseq...

Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.