Sleeping with Hippocampal Damage

Abstract

The hippocampus plays a critical role in sleep-related memory processes [1Maquet P. The role of sleep in learning and memory.Science. 2001; 294: 1048-1052Crossref PubMed Scopus (714) Google Scholar, 2Wilson M.A. McNaughton B.L. Reactivation of hippocampal ensemble memories during sleep.Science. 1994; 265: 676-679Crossref PubMed Scopus (1887) Google Scholar, 3Abel T. Havekes R. Saletin J.M. Walker M.P. Sleep, plasticity and memory from molecules to whole-brain networks.Curr. Biol. 2013; 23: R774-R788Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar], but it is unclear which specific sleep features are dependent upon this brain structure. The examination of sleep physiology in patients with focal bilateral hippocampal damage and amnesia could supply important evidence regarding these links. However, there is a dearth of such studies, despite these patients providing compelling insights into awake cognition [4Clark I.A. Maguire E.A. Remembering preservation in hippocampal amnesia.Annu. Rev. Psychol. 2016; 67: 51-82Crossref PubMed Scopus (40) Google Scholar, 5Spiers H.J. Maguire E.A. Burgess N. Hippocampal amnesia.Neurocase. 2001; 7: 357-382Crossref PubMed Scopus (206) Google Scholar]. Here, we sought to identify the contribution of the hippocampus to the sleep phenotype by characterizing sleep via comprehensive qualitative and quantitative analyses in memory-impaired patients with selective bilateral hippocampal damage and matched control participants using in-home polysomnography on 4 nights. We found that, compared to control participants, patients had significantly reduced slow-wave sleep—likely due to decreased density of slow waves—as well as slow-wave activity. In contrast, slow and fast spindles were indistinguishable from those of control participants. Moreover, patients expressed slow oscillations (SOs), and SO-fast spindle coupling was observed. However, on closer scrutiny, we noted that the timing of spindles within the SO cycle was delayed in the patients. The shift of patients’ spindles into the later phase of the up-state within the SO cycle may indicate a mismatch in timing across the SO-spindle-ripple events that are associated with memory consolidation [6Helfrich R.F. Mander B.A. Jagust W.J. Knight R.T. Walker M.P. Old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting.Neuron. 2018; 97: 221-230.e4Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar, 7Kim J. Gulati T. Ganguly K. Competing roles of slow oscillations and delta waves in memory consolidation versus forgetting.Cell. 2019; 179: 514-526.e13Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. The substantial effect of selective bilateral hippocampal damage on large-scale oscillatory activity in the cortex suggests that, as with awake cognition, the hippocampus plays a significant role in sleep physiology, which may, in turn, be necessary for efficacious episodic memory.