The Human Medial Temporal Lobe Is Necessary for Remembering Durations within a Sequence of Events but Not Durations of Individual Events

Recent interest in the role of the hippocampus in temporal aspects of cognition has been fueled, in part, by the observation of “time” cells in the rodent hippocampus—that is, cells that have differential firing patterns depending on how long ago an event occurred. Such cells are thought to provide an internal representation of elapsed time. Yet, the hippocampus is not needed for processing temporal duration information per se, at least on the order of seconds, as evidenced by intact duration judgments in rodents and humans with hippocampal damage. Rather, it has been proposed that the hippocampus may be essential for coding higher order aspects of temporal mnemonic processing, such as those needed to temporally organize a sequence of events that form an episode. To examine whether (1) the hippocampus uses duration information in the service of establishing temporal relations among events and (2) its role in memory for duration is unique to sequences, we tested amnesic patients with medial-temporal lobe damage (including the hippocampus). We hypothesized that medial-temporal lobe damage should impair the ability to remember sequential duration information but leave intact judgments about duration devoid of a sequential demand. We found that amnesics were impaired in making judgments about durations within a sequence but not in judging single durations. This impairment was not due to higher cognitive load associated with duration judgments about sequences. In convergence with rodent and human fMRI work, these findings shed light on how time coding in the hippocampus may contribute to temporal cognition.

[1]  Lila Davachi,et al.  Similarity Breeds Proximity: Pattern Similarity within and across Contexts Is Related to Later Mnemonic Judgments of Temporal Proximity , 2014, Neuron.

[2]  N. Fortin,et al.  Critical Role of the Hippocampus in Memory for Elapsed Time , 2013, The Journal of Neuroscience.

[3]  N. Fortin,et al.  Nonspatial Sequence Coding in CA1 Neurons , 2016, The Journal of Neuroscience.

[4]  R. Passingham The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[5]  John O. Willis,et al.  Wechsler Adult Intelligence Scale–Third Edition , 2008 .

[6]  Charan Ranganath,et al.  The hippocampus: a special place for time , 2016, Annals of the New York Academy of Sciences.

[7]  Marc W Howard,et al.  Human Episodic Memory Retrieval Is Accompanied by a Neural Contiguity Effect , 2018, The Journal of Neuroscience.

[8]  Ann M Graybiel,et al.  Neural representation of time in cortico-basal ganglia circuits , 2009, Proceedings of the National Academy of Sciences.

[9]  H. Eichenbaum,et al.  Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons , 2017, Neuron.

[10]  Arne D. Ekstrom,et al.  Close but no cigar: Spatial precision deficits following medial temporal lobe lesions provide novel insight into theoretical models of navigation and memory , 2018, Hippocampus.

[11]  N. Hunkin,et al.  Memory for single items, word pairs, and temporal order of different kinds in a patient with selective hippocampal lesions , 2001, Cognitive neuropsychology.

[12]  Andy C. H. Lee,et al.  Multivoxel pattern similarity suggests the integration of temporal duration in hippocampal event sequence representations , 2018, NeuroImage.

[13]  H. Eichenbaum,et al.  Critical role of the hippocampus in memory for sequences of events , 2002, Nature Neuroscience.

[14]  L. Davachi,et al.  What Constitutes an Episode in Episodic Memory? , 2011, Psychological science.

[15]  H. Eichenbaum,et al.  Distinct Hippocampal Time Cell Sequences Represent Odor Memories in Immobilized Rats , 2013, The Journal of Neuroscience.

[16]  Donna Kwan,et al.  Specific, personally meaningful cues can benefit episodic prospection in medial temporal lobe amnesia. , 2016, The British journal of clinical psychology.

[17]  Joseph J. Paton,et al.  A Scalable Population Code for Time in the Striatum , 2015, Current Biology.

[18]  M. Verfaellie,et al.  Does the hippocampus keep track of time? , 2016, Hippocampus.

[19]  Joshua D Koen,et al.  Visual short‐term memory for high resolution associations is impaired in patients with medial temporal lobe damage , 2017, Hippocampus.

[20]  Zachariah M. Reagh,et al.  Precise temporal memories are supported by the lateral entorhinal cortex in humans , 2019, Nature Neuroscience.

[21]  Matthew L Shapiro,et al.  Memory Time , 2011, Neuron.

[22]  Christian F. Doeller,et al.  Structuring Time in Human Lateral Entorhinal Cortex , 2018, bioRxiv.

[23]  L. Davachi,et al.  Transcending time in the brain: How event memories are constructed from experience , 2019, Hippocampus.

[24]  Marc W Howard,et al.  The Same Hippocampal CA1 Population Simultaneously Codes Temporal Information over Multiple Timescales , 2018, Current Biology.

[25]  Li Lu,et al.  Integrating time from experience in the lateral entorhinal cortex , 2018, Nature.

[26]  Lila Davachi,et al.  How the hippocampus preserves order: the role of prediction and context , 2015, Trends in Cognitive Sciences.

[27]  H. Eichenbaum The hippocampus and declarative memory: cognitive mechanisms and neural codes , 2001, Behavioural Brain Research.

[28]  Arne D. Ekstrom,et al.  A Tale of Two Temporal Coding Strategies: Common and Dissociable Brain Regions Involved in Recency versus Associative Temporal Order Retrieval Strategies , 2017, Journal of Cognitive Neuroscience.

[29]  Felicia A. Huppert,et al.  The Role of Trace Strength in Recency and Frequency Judgements by Amnesic and Control Subjects , 1978, The Quarterly journal of experimental psychology.

[30]  Bon-Mi Gu,et al.  The persistence of memory: how the brain encodes time in memory , 2017, Current Opinion in Behavioral Sciences.

[31]  Thomas Wolbers,et al.  The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories , 2016, Current Biology.

[32]  G. Buzsáki,et al.  Space and Time: The Hippocampus as a Sequence Generator , 2018, Trends in Cognitive Sciences.

[33]  Andy C. H. Lee,et al.  The human hippocampus is sensitive to the durations of events and intervals within a sequence , 2014, Neuropsychologia.

[34]  H. Eichenbaum,et al.  Hippocampal “Time Cells” Bridge the Gap in Memory for Discontiguous Events , 2011, Neuron.

[35]  Marc W. Howard,et al.  Medial Temporal Lobe Amnesia Is Associated with a Deficit in Recovering Temporal Context , 2019, Journal of Cognitive Neuroscience.

[36]  Charan Ranganath,et al.  Distinct neural mechanisms for remembering when an event occurred , 2016, Hippocampus.

[37]  Andy C H Lee,et al.  Evidence for the incorporation of temporal duration information in human hippocampal long-term memory sequence representations , 2019, Proceedings of the National Academy of Sciences.

[38]  Mieke Verfaellie,et al.  Hippocampal contributions to memory for time: evidence from neuropsychological studies , 2017, Current Opinion in Behavioral Sciences.

[39]  A. Yonelinas The hippocampus supports high-resolution binding in the service of perception, working memory and long-term memory , 2013, Behavioural Brain Research.

[40]  Howard L. Kaplan,et al.  Tables of d′ for variable-standard discrimination paradigms , 1978 .

[41]  Christian F. Doeller,et al.  Mapping sequence structure in the human lateral entorhinal cortex , 2019, eLife.

[42]  Larry R Squire,et al.  Intact Working Memory for Relational Information after Medial Temporal Lobe Damage , 2010, The Journal of Neuroscience.

[43]  Earl K. Miller,et al.  Compressed Timeline of Recent Experience in Monkey Lateral Prefrontal Cortex , 2018, Journal of Cognitive Neuroscience.

[44]  Marc W. Howard,et al.  Associative Retrieval Processes in Episodic Memory , 2008 .

[45]  Natasa Kovacevic,et al.  Patterns of Autobiographical Memory Loss in Medial-Temporal Lobe Amnesic Patients , 2008, Journal of Cognitive Neuroscience.

[46]  Asohan Amarasingham,et al.  Hippocampus Internally Generated Cell Assembly Sequences in the Rat , 2011 .

[47]  Lily Riggs,et al.  The hippocampus supports multiple cognitive processes through relational binding and comparison , 2012, Front. Hum. Neurosci..

[48]  Adam W. McCrimmon,et al.  Review of the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) , 2013 .

[49]  Sandra N. Moses,et al.  Relational learning and transitive expression in aging and amnesia , 2015, Hippocampus.

[50]  Andy C. H. Lee,et al.  The hippocampus and visual perception , 2012, Front. Hum. Neurosci..

[51]  P. R. Meudell,et al.  Why are Amnesic Judgements of Recency and Frequency Made in a Qualitatively Different Way from those of Normal People? , 1989, Cortex.

[52]  M. Botvinick,et al.  Statistical learning of temporal community structure in the hippocampus , 2016, Hippocampus.

[53]  Nikos Makris,et al.  Role of the medial temporal lobes in relational memory: Neuropsychological evidence from a cued recognition paradigm , 2007, Neuropsychologia.

[54]  D. Kumaran,et al.  An Unexpected Sequence of Events: Mismatch Detection in the Human Hippocampus , 2006, PLoS biology.

[55]  Paul H Garthwaite,et al.  Comparison of a single case to a control or normative sample in neuropsychology: Development of a Bayesian approach , 2007, Cognitive neuropsychology.

[56]  C. Ranganath,et al.  Prefrontal and Medial Temporal Lobe Activity at Encoding Predicts Temporal Context Memory , 2010, The Journal of Neuroscience.

[57]  L. Davachi,et al.  Temporal Memory Is Shaped by Encoding Stability and Intervening Item Reactivation , 2014, The Journal of Neuroscience.

[58]  Asohan Amarasingham,et al.  Internally Generated Cell Assembly Sequences in the Rat Hippocampus , 2008, Science.

[59]  Marc W Howard,et al.  The temporal context model in spatial navigation and relational learning: toward a common explanation of medial temporal lobe function across domains. , 2005, Psychological review.

[60]  Marc W Howard,et al.  Time and space in the hippocampus , 2015, Brain Research.

[61]  R. Clark,et al.  The medial temporal lobe. , 2004, Annual review of neuroscience.

[62]  Matthias J. Gruber,et al.  Hippocampal Activity Patterns Carry Information about Objects in Temporal Context , 2014, Neuron.

[63]  Morris Moscovitch,et al.  Medial temporal lobe amnesia impairs performance on a free association task , 2013, Hippocampus.