RESEARCH ARTICLE SUMMARY
◥NEUROSCIENCE
Hippocampal sharp-wave ripples
linked to visual episodic recollection
in humans
Yitzhak Norman, Erin M. Yeagle, Simon Khuvis, Michal Harel,
Ashesh D. Mehta, Rafael Malach*
INTRODUCTION:Sharp-wave ripples (SWRs)
are rapid bursts of synchronized neuronal ac-
tivity elicited by the hippocampus. Extensive
study of SWRs, mainly in the rodent brain, has
linked these bursts to navigation, memory for-
mation, and offline memory consolidation. How-
ever, fundamental questions remain regarding
the functional meaning of this striking exam-
ple of network synchrony. Perhaps the most
glaring unknown is the relationship betweenSWRs and conscious cognition. We still do
not know what cognitive process, if any, is
linked to the emergence of SWRs; to put it
simply, we still do not know what an animal
thinks about (if anything) when the hip-
pocampus elicits a ripple. Furthermore, the
potential role of SWRs in human episodic
memory is still largely unknown. Thus, study-
ing this phenomenon in conscious, awake
human patients opens a unique window, as
it allows direct examination of detailed verbal
reports with respect to SWR occurrences.RATIONALE:We took advantage of the unique
ability of humans to communicate verbally
about their inner cognitive state to exam-
ine the role of SWRs in
memory formation and
retrieval, using intracranial
electrophysiological re-
cordings in patients. This
approach allowed us to
study free recall, the pro-
cess of self-initiated, inter-
nal generation of memories. It is a uniquely
powerful approach because it isolates the
process of recall from external stimulation.RESULTS:Our study revealed three major
aspects linking SWRs to human declarative
memory. First, the SWR rate during picture
viewing (i.e., memory encoding) predicted
subjects’subsequent free-recall performance.
Second, a transient increase in SWR rate pre-
ceded the verbal report of recall by 1 to 2 s.
This increase was content-selective, recapitu-
lating the same picture preferences observed
during viewing. Finally, during recollection,
high-order visual areas showed content-selective
reactivation coupled to SWR emission.CONCLUSION:By direct recordings of electro-
physiological events in the brains of individuals
who could inform, in real time, on their cogni-
tive state, we were able to demonstrate and
characterize an important role of SWRs in
human episodic memory. Our findings point
to the involvement of hippocampal SWRs in
establishing and triggering spontaneous re-
collections in the human brain. They implicate
SWRs in the process of engraving new memo-
ries, and reveal their fundamental contribution
in orchestrating the dialogue between memory
centers (hippocampus) and high-level repre-
sentations (cerebral cortex), which underlies
the retrieval of these memories. Our study thus
highlights the function of SWRs as powerful
multitasking signals that contribute both to
the encoding and to the spontaneous access
and reinstatement of human memories.▪RESEARCH
Normanet al.,Science 365 , 657 (2019) 16 August 2019 1of1
The list of author affiliations is available in the full article online.
*Corresponding author. Email: [email protected]
Cite this article as Y. Normanet al.,Science 365 , eaax1030
(2019). DOI: 10.1126/science.aax1030SWR-coupled re-activation of visual cortex during recall:
Category-selective
visual electrodes (n = 57 bipoles)DdB-0.400.4dB-0.400.4Time from picture onset (ms) Time from SWR onset (ms)00.30 1000 2000 −400 0 400dB-404024 PreferredNon-preferreddB-404
100200100200Free recallnon-preferredpreferredFrequency (Hz)preferred imagesnon-preferred images100200100200Picture viewingCortical activation HFB power (dB)B Free recall
1500 ms750 ms1500 msPicture viewingCHippocampal Sharp Wave Ripples (SWR) re-activation during recall:
Left HippocampusAP0.2 mV100 ms10 μVSWRPicture viewing Free recallTime from verbal recall onset (ms)0.30.6Time from picture onset (ms)00.51SWR rate (events/sec) 0 1000 2000 -4000 04000High-RR images Low-RR imagesCA1 electrodeRaw LFPSWRRipple bandAHippocampal
electrodesCortical
electrodesIntra-cranial recordingsMemory reactivation coupled to hippocampal ripples during free recall.(A) Simultaneous
intracranial recordings in hippocampus and cortex. (B) Patients first viewed and then freely
recalled photographs of famous faces and places. (C) Rapid hippocampal neuronal bursts
(SWRs) were identified (left). When patients freely recalled the images, a transient increase in
SWR rate anticipated the onset of recall, dominated by items that generated a higher ripple
rate (RR) during viewing (compare red and black lines). (D) Visual areas in the cortex showed
SWR-coupled reactivation, recapitulating the content selectivity observed during viewing.
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