Widespread ripples synchronize human cortical activity during sleep, waking, and memory recall
Authors: Dickey Charles W. , Verzhbinsky Ilya A. , Jiang Xi , Rosen Burke Q. , Kajfez Sophie , Stedelin Brittany , Shih Jerry J. , Ben-Haim Sharona , Raslan Ahmed M. , Eskandar Emad N. , Gonzalez-Martinez Jorge , Cash Sydney S. , Halgren Eric 
Published: February 2021

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such ‘binding’ of different components of mental events into unified representations occurs is unknown. The ‘binding-bysynchrony’ theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations (‘ripples’) occur in the hippocampus and cortex, and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ~70ms duration 90Hz ripples often couple (within ±500ms), co-occur (≥25ms overlap), and crucially, phase-lock (have consistent phase-lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phaselocking increases with more cortical sites co-rippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase-lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical co-ripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and co-ripples increase high-frequency correlations between areas, suggesting synchronized unit-spiking facilitating information exchange. Co-occurrence, phasesynchrony, and high-frequency correlation are maintained with little decrement over very long distances (25cm). Hippocampo-cortico-cortical co-ripples appear to possess the essential properties necessary to support binding-by-synchrony during memory retrieval, and perhaps generally in cognition.

Significance Statement

Different elements of a memory, or any mental event, are encoded in locations distributed across the cortex. A prominent hypothesis proposes that widespread networks are integrated with bursts of synchronized high-frequency oscillations called ‘ripples,’ but evidence is limited. Here, using recordings inside the human brain, we show that ripples occur simultaneously in multiple lobes in both cortical hemispheres, and the hippocampus, generally during sleep and waking, and especially during memory recall. Ripples phase-lock local cell firing, and phase-synchronize with little decay between locations separated by up to 25cm, enabling long-distance integration. Indeed, co-rippling sites have increased correlation of very high-frequency activity which reflects cell firing. Thus, ripples may help bind information across the cortex in memory and other mental events.