Ensembles of human MTL neurons “jump back in time” in response to a repeated stimulus

Episodic memory, which depends critically on the integrity of the medial temporal lobe (MTL), has been described as “mental time travel” in which the rememberer “jumps back in time.” The neural mechanism underlying this ability remains elusive. Mathematical and computational models of performance in episodic memory tasks provide a specific hypothesis regarding the computation that supports such a jump back in time. The models suggest that a representation of temporal context, a representation that changes gradually over macroscopic periods of time, is the cue for episodic recall. According to these models, a jump back in time corresponds to a stimulus recovering a prior state of temporal context. In vivo single‐neuron recordings were taken from the human MTL while epilepsy patients distinguished novel from repeated images in a continuous recognition memory task. The firing pattern of the ensemble of MTL neurons showed robust temporal autocorrelation over macroscopic periods of time during performance of the memory task. The gradually‐changing part of the ensemble state was causally affected by the visual stimulus being presented. Critically, repetition of a stimulus caused the ensemble to elicit a pattern of activity that resembled the pattern of activity present before the initial presentation of the stimulus. These findings confirm a direct prediction of this class of temporal context models and may be a signature of the mechanism that underlies the experience of episodic memory as mental time travel. © 2012 Wiley Periodicals, Inc.

[1]  D Marr,et al.  Simple memory: a theory for archicortex. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

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

[3]  Marc W. Howard,et al.  Constructing Semantic Representations From a Gradually Changing Representation of Temporal Context , 2011, Top. Cogn. Sci..

[4]  E. Rolls,et al.  A computational theory of hippocampal function, and empirical tests of the theory , 2006, Progress in Neurobiology.

[5]  Xiao-Jing Wang.  Synaptic reverberation underlying mnemonic persistent activity , 2001, Trends in Neurosciences.

[6]  Y. Miyashita,et al.  Backward spreading of memory-retrieval signal in the primate temporal cortex. , 2001, Science.

[7]  Arne D. Ekstrom,et al.  Cellular networks underlying human spatial navigation , 2003, Nature.

[8]  M. Quirk,et al.  Experience-Dependent Asymmetric Shape of Hippocampal Receptive Fields , 2000, Neuron.

[9]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[10]  M. Usher,et al.  The demise of short-term memory revisited: empirical and computational investigations of recency effects. , 2005, Psychological review.

[11]  Evgueniy V. Lubenov,et al.  Prefrontal Phase Locking to Hippocampal Theta Oscillations , 2005, Neuron.

[12]  Yevgeniy B. Sirotin,et al.  Going beyond a single list: Modeling the effects of prior experience on episodic free recall , 2005, Psychonomic bulletin & review.

[13]  David Wood,et al.  Luddites must not block progress in genetics , 1999, Nature.

[14]  Michael E Hasselmo,et al.  Persistent Firing Supported by an Intrinsic Cellular Mechanism in a Component of the Head Direction System , 2009, The Journal of Neuroscience.

[15]  Tony A. Fields,et al.  Cerebral microdialysis combined with single-neuron and electroencephalographic recording in neurosurgical patients. Technical note. , 1999, Journal of neurosurgery.

[16]  Vinayak A. Rao,et al.  Retrieved context and the discovery of semantic structure , 2007, NIPS.

[17]  M. Hasselmo.  Arc length coding by interference of theta frequency oscillations may underlie context-dependent hippocampal unit data and episodic memory function. , 2007, Learning & memory.

[18]  A. Egorov,et al.  Muscarinic control of graded persistent activity in lateral amygdala neurons , 2006, The European journal of neuroscience.

[19]  S. Grossberg,et al.  A neural network model of adaptively timed reinforcement learning and hippocampal dynamics. , 1992, Brain research. Cognitive brain research.

[20]  Marc W Howard,et al.  Gradual Changes in Hippocampal Activity Support Remembering the Order of Events , 2007, Neuron.

[21]  K. Meador,et al.  Theta oscillations mediate interaction between prefrontal cortex and medial temporal lobe in human memory. , 2010, Cerebral cortex.

[22]  M. Hasselmo,et al.  Graded persistent activity in entorhinal cortex neurons , 2002, Nature.

[23]  Vinayak A. Rao,et al.  Bridging the gap: transitive associations between items presented in similar temporal contexts. , 2009, Journal of experimental psychology. Learning, memory, and cognition.

[24]  Philippe Séguéla,et al.  Metabotropic induction of persistent activity in layers II/III of anterior cingulate cortex. , 2010, Cerebral cortex.

[25]  C. Koch,et al.  Invariant visual representation by single neurons in the human brain , 2005, Nature.

[26]  R. Ratcliff,et al.  Retrieval Processes in Recognition Memory , 1976 .

[27]  E. Tulving,et al.  Memory and Verbal Learning , 1970 .

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

[29]  Richard C. Atkinson,et al.  Human Memory: A Proposed System and its Control Processes , 1968, Psychology of Learning and Motivation.

[30]  E. Raskin,et al.  The strength and direction of associations formed in the learning of nonsense syllables , 1937 .

[31]  Brenda Milner,et al.  The frontal cortex and memory for temporal order , 1991, Neuropsychologia.

[32]  J. Raaijmakers,et al.  A model for interference and forgetting , 1988 .

[33]  G. Ward,et al.  Time scale similarity and long-term memory for autobiographical events , 2010, Psychonomic bulletin & review.

[34]  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.

[35]  M. Humphreys,et al.  A context noise model of episodic word recognition. , 2001, Psychological review.

[36]  T. H. Brown,et al.  Muscarinic receptor activation enables persistent firing in pyramidal neurons from superficial layers of dorsal perirhinal cortex , 2012, Hippocampus.

[37]  R. Quian Quiroga,et al.  Unsupervised Spike Detection and Sorting with Wavelets and Superparamagnetic Clustering , 2004, Neural Computation.

[38]  W. Estes.  Statistical theory of spontaneous recovery and regression. , 1955, Psychological review.

[39]  Michael E Hasselmo,et al.  Mglur-dependent Persistent Firing in Entorhinal Cortex Layer Iii Neurons , 2022 .

[40]  Sean M. Polyn,et al.  Memory search and the neural representation of context , 2008, Trends in Cognitive Sciences.

[41]  Michael E Hasselmo,et al.  First-in-first-out item replacement in a model of short-term memory based on persistent spiking. , 2007, Cerebral cortex.

[42]  Rodrigo Quian Quiroga,et al.  Human medial temporal lobe neurons respond preferentially to personally relevant images , 2009, Proceedings of the National Academy of Sciences.

[43]  E. Halgren,et al.  Neural encoding of individual words and faces by the human hippocampus and amygdala , 1988, Nature.

[44]  I. Fried,et al.  Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall , 2008, Science.

[45]  Y. Miyashita.  Neuronal correlate of visual associative long-term memory in the primate temporal cortex , 1988, Nature.

[46]  Richard M. Shiffrin,et al.  SAM: A theory of probabilistic search in associative memory. , 1980 .

[47]  H. Spiers,et al.  Prefrontal and medial temporal lobe interactions in long-term memory , 2003, Nature Reviews Neuroscience.

[48]  M. Eckardt.  The Hippocampus as a Cognitive Map , 1980 .

[49]  M. Hasselmo,et al.  Switching between “On” and “Off” states of persistent activity in lateral entorhinal layer III neurons , 2007, Hippocampus.

[50]  N. Spruston,et al.  Slow integration leads to persistent action potential firing in distal axons of coupled interneurons , 2010, Nature Neuroscience.

[51]  Marc W. Howard,et al.  A distributed representation of temporal context , 2002 .

[52]  H. Eichenbaum,et al.  The medial temporal lobe and recognition memory. , 2007, Annual review of neuroscience.

[53]  S. Grossberg,et al.  Laminar cortical dynamics of cognitive and motor working memory, sequence learning and performance: toward a unified theory of how the cerebral cortex works. , 2008, Psychological review.

[54]  G D Brown,et al.  Oscillator-based memory for serial order. , 2000, Psychological review.

[55]  B. McNaughton,et al.  Hippocampal synaptic enhancement and information storage within a distributed memory system , 1987, Trends in Neurosciences.

[56]  Terrence R Stanford,et al.  Categorization in the monkey hippocampus: a possible mechanism for encoding information into memory. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Itzhak Fried,et al.  Differences in Mnemonic Processing by Neurons in the Human Hippocampus and Parahippocampal Regions , 2006, Journal of Cognitive Neuroscience.

[58]  Marc W Howard,et al.  The persistence of memory: Contiguity effects across hundreds of seconds , 2008, Psychonomic bulletin & review.

[59]  M. Kahana.  Associative retrieval processes in free recall , 1996, Memory & cognition.

[60]  Y. Naya,et al.  Integrating What and When Across the Primate Medial Temporal Lobe , 2011, Science.

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

[62]  T. Sejnowski,et al.  Neurocomputational models of working memory , 2000, Nature Neuroscience.

[63]  M. Bradley,et al.  A two-process account of long-term serial position effects , 1980 .

[64]  J. Lisman.  Relating Hippocampal Circuitry to Function Recall of Memory Sequences by Reciprocal Dentate–CA3 Interactions , 1999, Neuron.

[65]  B. Murdock.  Context and mediators in a theory of distributed associative memory (TODAM2). , 1997 .

[66]  J. Byrne.  Learning and memory : a comprehensive reference , 2008 .

[67]  J. Lisman,et al.  Hippocampal sequence-encoding driven by a cortical multi-item working memory buffer , 2005, Trends in Neurosciences.

[68]  R. O’Reilly,et al.  Modeling hippocampal and neocortical contributions to recognition memory: a complementary-learning-systems approach. , 2003, Psychological review.

[69]  M. Hasselmo,et al.  Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function , 1997, Behavioural Brain Research.

[70]  Marc W. Howard,et al.  A Scale-Invariant Internal Representation of Time , 2012, Neural Computation.

[71]  Per B Sederberg,et al.  The temporal contiguity effect predicts episodic memory performance. , 2010, Memory & cognition.

[72]  Jeremy R. Manning,et al.  Oscillatory patterns in temporal lobe reveal context reinstatement during memory search , 2011, Proceedings of the National Academy of Sciences.

[73]  Sean M. Polyn,et al.  Human memory reconsolidation can be explained using the temporal context model , 2011, Psychonomic bulletin & review.

[74]  M. Hasselmo,et al.  Mechanism of Graded Persistent Cellular Activity of Entorhinal Cortex Layer V Neurons , 2006, Neuron.

[75]  R. Shiffrin,et al.  A model for recognition memory: REM—retrieving effectively from memory , 1997, Psychonomic bulletin & review.

[76]  H. Eichenbaum,et al.  The global record of memory in hippocampal neuronal activity , 1999, Nature.

[77]  N. Unsworth.  Exploring the Retrieval Dynamics of Delayed and Final Free Recall: Further Evidence for Temporal-Contextual Search. , 2008 .

[78]  G. Mandler,et al.  Retrieval processes in recognition , 1974, Memory & cognition.

[79]  Sean M. Polyn,et al.  A context maintenance and retrieval model of organizational processes in free recall. , 2009, Psychological review.

[80]  J. Caplan,et al.  Precise instructions determine participants’ memory search strategy in judgments of relative order in short lists , 2009, Psychonomic bulletin & review.

[81]  Arthur P. Shimamura,et al.  Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients , 1990, Neuropsychologia.

[82]  N. Burgess.  Memory for Serial Order : A Network Model of the Phonological Loop and its Timing , 1999 .

[83]  Murdock,et al.  The serial position effect of free recall , 1962 .

[84]  Rafael Malach,et al.  A neural substrate in the human hippocampus for linking successive events , 2010, Proceedings of the National Academy of Sciences.

[85]  Marc W Howard,et al.  A context-based theory of recency and contiguity in free recall. , 2008, Psychological review.

[86]  Marc W Howard,et al.  Reply to Farrell and Lewandowsky: Recency—contiguity interactions predicted by the temporal context model , 2009, Psychonomic bulletin & review.

[87]  Michael J. Hacker.  Speed and accuracy of recency judgments for events in short-term memory. , 1980 .