Coupled Ripple Oscillations Retrieve Human Memory Science  1 March 2019:Vol. 364, Issue 6445, pp. 1082-1086DOI: 10.1126/science.aax0758 Coupled Ripple Oscillations between the Medial Temporal Lobe and Neocortex Retrieve Human Memory Alex F. Vax, et.al. Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. Medical Scientist Training Program, Duke University School of Medicine, Durham, NC 27710, USA. Department of Neurobiology, Duke University, Durham, NC 27710, USA. Office of the Clinical Director, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. Department of Physics, Duke University, Durham, NC 27710, USA [paraphrase] Episodic memory retrieval relies on the recovery of neural representations of waking experience. This process is thought to involve a communication dynamic between the medial temporal lobe memory system and the neocortex. How this occurs is largely unknown, however, especially as it pertains to awake human memory retrieval. Using intracranial electroencephalographic recordings, we found that ripple oscillations were dynamically coupled between the human medial temporal lobe (MTL) and temporal association cortex. Coupled ripples were more pronounced during successful verbal memory retrieval and recover the cortical neural representations of remembered items. Together, these data provide direct evidence that coupled ripples between the MTL and association cortex may underlie successful memory retrieval in the human brain. The medial temporal lobe (MTL) plays a critical role in episodic memory formation, yet successful memory retrieval also involves recovering neural representations that were present in the cortex when memories were first experienced. This has led to the hypothesis that the MTL may promote episodic memory retrieval through a dialogue with the cortex that recovers these neural representations, although how this occurs is unknown. One possibility is that such a dialogue may be coordinated through fast oscillations termed ripples that have been implicated in learning and memory across species. Ripples in the rodent hippocampus and MTL structures are important for memory consolidation while awake and asleep and are associated with memory replay. MTL ripples may indeed coordinate neural activity in cortical regions, and hippocampal ripples are coupled to ripples that have also been identified in the cortex in a learning- dependent manner. Human hippocampal ripples during sleep have been linked to memory consolidation, but it remains unknown whether such ripples are relevant for awake human memory retrieval. Moreover, it is unknown if cortical and hippocampal ripples in humans are temporally coordinated and if such coordination may play a role in promoting successful memory retrieval. To examine this possibility, we analyzed intracranial electroencephalography (iEEG) signals from subdural electrodes placed along the MTL, as well as in other areas of cortex, in 14 participants (9 female; 36.2 ± 3.0 years) with drug-resistant epilepsy as they performed a paired associates verbal episodic memory task. We found several examples of ripple oscillations occurring simultaneously between the MTL and sites in the lateral temporal cortex. Given the easily visualized ripples in the iEEG signals and the narrow-band power spectral density peaks present within single electrodes in the MTL, we extracted ripples in the 80- to 120-Hz band (mean baseline MTL ripple rate of 0.21 ± 0.02 Hz across participants), which is consistent with previous reports of human ripple activity in these frequencies Our data demonstrate that increased ripples within the human MTL that are coupled with the neocortex mediate successful memory retrieval. Our results therefore build upon previous studies implicating ripples in memory in three important ways. First, we demonstrate that awake memory retrieval in humans involves a significant increase in ripple oscillations in the 80- to 120-Hz frequency range in the MTL. Second, we specifically show that the increased ripples in the MTL are coupled with ripples in the temporal association cortex. Third, we directly link coupled ripples to the reinstatement of cortical neural activity that was present during encoding. Taken together, our data provide direct evidence for and insights into the neural mechanisms of memory retrieval and suggest that coupled ripples may constitute a neural mechanism for actively retrieving memory representations in the human brain. [end of paraphrase]   Return to — Hippocampus