Mesoscopic Neural Representations in Spatial Navigation

Recent evidence suggests that mesoscopic neural oscillations measured via intracranial electroencephalography exhibit spatial representations, which were previously only observed at the micro- and macroscopic level of brain organization. Specifically, theta (and gamma) oscillations correlate with movement, speed, distance, specific locations, and goal proximity to boundaries. In entorhinal cortex (EC), they exhibit hexadirectional modulation, which is putatively linked to grid cell activity. Understanding this mesoscopic neural code is crucial because information represented by oscillatory power and phase may complement the information content at other levels of brain organization. Mesoscopic neural oscillations help bridge the gap between single-neuron and macroscopic brain signals of spatial navigation and may provide a mechanistic basis for novel biomarkers and therapeutic targets to treat diseases causing spatial disorientation.

[1]  Andreas Schulze-Bonhage,et al.  Hexadirectional Modulation of Theta Power in Human Entorhinal Cortex during Spatial Navigation , 2018, Current Biology.

[2]  Arne D. Ekstrom,et al.  Correlation between BOLD fMRI and theta-band local field potentials in the human hippocampal area. , 2009, Journal of neurophysiology.

[3]  W. Singer,et al.  Hemodynamic Signals Correlate Tightly with Synchronized Gamma Oscillations , 2005, Science.

[4]  Alexandra T. Keinath,et al.  The Preferred Directions of Conjunctive Grid X Head Direction Cells in the Medial Entorhinal Cortex Are Periodically Organized , 2016, PloS one.

[5]  Neil Burgess,et al.  A Computational Model of Visual Recognition Memory via Grid Cells , 2019, Current Biology.

[6]  K. Grill-Spector,et al.  Repetition and the brain: neural models of stimulus-specific effects , 2006, Trends in Cognitive Sciences.

[7]  Torkel Hafting,et al.  Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex , 2006, Science.

[8]  Shachar Maidenbaum,et al.  Grid-like hexadirectional modulation of human entorhinal theta oscillations , 2018, Proceedings of the National Academy of Sciences.

[9]  Thomas J. Wills,et al.  Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model , 2008, Proceedings of the National Academy of Sciences.

[10]  M. Moser,et al.  Representation of Geometric Borders in the Entorhinal Cortex , 2008, Science.

[11]  Benjamin J. Kraus,et al.  Hippocampal “Time Cells”: Time versus Path Integration , 2013, Neuron.

[12]  K. Jeffery,et al.  Anisotropic encoding of three-dimensional space by place cells and grid cells , 2011, Nature Neuroscience.

[13]  Katrina Ferrara,et al.  Neural representation of scene boundaries , 2016, Neuropsychologia.

[14]  Jan Laczó,et al.  Behavioral Neuroscience Mini Review Article Neural Correlates of Spatial Navigation Changes in Mild Cognitive Impairment and Alzheimer's Disease , 2022 .

[15]  T. Hafting,et al.  Hippocampus-independent phase precession in entorhinal grid cells , 2008, Nature.

[16]  Jakub Hort,et al.  Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease? , 2018, Nature Reviews Neurology.

[17]  Lukas Kunz,et al.  Reduced grid-cell–like representations in adults at genetic risk for Alzheimer’s disease , 2015, Science.

[18]  M. A. Smith,et al.  Stimulus Selectivity and Spatial Coherence of Gamma Components of the Local Field Potential , 2011, The Journal of Neuroscience.

[19]  Kei M. Igarashi,et al.  Impaired In Vivo Gamma Oscillations in the Medial Entorhinal Cortex of Knock-in Alzheimer Model , 2017, Front. Syst. Neurosci..

[20]  L. Lemieux,et al.  Electrophysiological correlates of the BOLD signal for EEG‐informed fMRI , 2014, Human brain mapping.

[21]  R. Muller,et al.  Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  G. Buzsáki,et al.  Phase relations of hippocampal projection cells and interneurons to theta activity in the anesthetized rat , 1983, Brain Research.

[23]  Andrew J. Watrous,et al.  Functionally distinct high and low theta oscillations in the human hippocampus , 2018, bioRxiv.

[24]  Laura Lee Colgin,et al.  Impairments in spatial representations and rhythmic coordination of place cells in the 3xTg mouse model of Alzheimer's disease , 2017, Hippocampus.

[25]  Edvard I. Moser,et al.  Speed cells in the medial entorhinal cortex , 2015, Nature.

[26]  Andrew M. Wikenheiser,et al.  Hippocampal theta sequences reflect current goals , 2015, Nature Neuroscience.

[27]  Hanbing Lu,et al.  Delta Rhythm Orchestrates the Neural Activity Underlying the Resting State BOLD Signal via Phase–amplitude Coupling , 2019, Cerebral cortex.

[28]  T. Hafting,et al.  Frequency of gamma oscillations routes flow of information in the hippocampus , 2009, Nature.

[29]  Ole Jensen,et al.  Reading the hippocampal code by theta phase-locking , 2005, Trends in Cognitive Sciences.

[30]  Arne D. Ekstrom,et al.  Brain Oscillations Control Timing of Single-Neuron Activity in Humans , 2007, The Journal of Neuroscience.

[31]  Brian Litt,et al.  Right-lateralized Brain Oscillations in Human Spatial Navigation , 2010, Journal of Cognitive Neuroscience.

[32]  S. Kasicki,et al.  The frequency of rat's hippocampal theta rhythm is related to the speed of locomotion , 1998, Brain Research.

[33]  Arne D. Ekstrom,et al.  Interacting networks of brain regions underlie human spatial navigation: a review and novel synthesis of the literature. , 2017, Journal of neurophysiology.

[34]  Tobias Staudigl,et al.  Hexadirectional Modulation of High-Frequency Electrophysiological Activity in the Human Anterior Medial Temporal Lobe Maps Visual Space , 2018, Current Biology.

[35]  R U Muller,et al.  Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[37]  Bart Gips,et al.  Temporal coding organized by coupled alpha and gamma oscillations prioritize visual processing , 2014, Trends in Neurosciences.

[38]  Marco Leite,et al.  Phase–amplitude coupling and the BOLD signal: A simultaneous intracranial EEG (icEEG) - fMRI study in humans performing a finger-tapping task , 2017, NeuroImage.

[39]  T. McNamara,et al.  Egocentric and geocentric frames of reference in memory of large-scale space , 2003, Psychonomic bulletin & review.

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

[41]  J. Fell,et al.  Cross-frequency coupling supports multi-item working memory in the human hippocampus , 2010, Proceedings of the National Academy of Sciences.

[42]  C. Barnes,et al.  The Aging Navigational System , 2017, Neuron.

[43]  Ian H. Stevenson,et al.  Spatially Distributed Local Fields in the Hippocampus Encode Rat Position , 2014, Science.

[44]  Jean Gotman,et al.  Low-frequency theta oscillations in the human hippocampus during real-world and virtual navigation , 2017, Nature Communications.

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

[46]  N. Burgess,et al.  The Cognitive Architecture of Spatial Navigation: Hippocampal and Striatal Contributions , 2015, Neuron.

[47]  N. Burgess,et al.  Human hippocampal theta power indicates movement onset and distance travelled , 2017, Proceedings of the National Academy of Sciences.

[48]  E Save,et al.  Evidence for a relationship between place‐cell spatial firing and spatial memory performance , 2001, Hippocampus.

[49]  E. Niebur,et al.  Neural Correlates of High-Gamma Oscillations (60–200 Hz) in Macaque Local Field Potentials and Their Potential Implications in Electrocorticography , 2008, The Journal of Neuroscience.

[50]  Bryan C. Souza,et al.  Asymmetry of the temporal code for space by hippocampal place cells , 2016, Scientific Reports.

[51]  J. Maunsell,et al.  Different Origins of Gamma Rhythm and High-Gamma Activity in Macaque Visual Cortex , 2011, PLoS biology.

[52]  Zeb Kurth-Nelson,et al.  What Is a Cognitive Map? Organizing Knowledge for Flexible Behavior , 2018, Neuron.

[53]  Russell A. Epstein,et al.  Anchoring the neural compass: Coding of local spatial reference frames in human medial parietal lobe , 2014, Nature Neuroscience.

[54]  Jonathan Miller,et al.  Phase-tuned neuronal firing encodes human contextual representations for navigational goals , 2017, bioRxiv.

[55]  N. Logothetis What we can do and what we cannot do with fMRI , 2008, Nature.

[56]  N. Ulanovsky,et al.  Social place-cells in the bat hippocampus , 2018, Science.

[57]  H. Teitelbaum,et al.  Relationship between hippocampal theta activity and running speed in the rat. , 1975, Journal of comparative and physiological psychology.

[58]  John O'Keefe,et al.  Independent rate and temporal coding in hippocampal pyramidal cells , 2003, Nature.

[59]  I. Fried,et al.  Coupling Between Neuronal Firing, Field Potentials, and fMRI in Human Auditory Cortex , 2005, Science.

[60]  J. O’Keefe,et al.  Geometric determinants of the place fields of hippocampal neurons , 1996, Nature.

[61]  Brad E. Pfeiffer,et al.  Hippocampal place cell sequences depict future paths to remembered goals , 2013, Nature.

[62]  D. Tank,et al.  A Map-like Micro-Organization of Grid Cells in the Medial Entorhinal Cortex , 2018, Cell.

[63]  I. Fried,et al.  Coupling between Neuronal Firing Rate, Gamma LFP, and BOLD fMRI Is Related to Interneuronal Correlations , 2007, Current Biology.

[64]  Surya Ganguli,et al.  Environmental Boundaries as an Error Correction Mechanism for Grid Cells , 2015, Neuron.

[65]  Grace M. Hwang,et al.  Cognitive swarming in complex environments with attractor dynamics and oscillatory computing , 2019, Biological Cybernetics.

[66]  G. Buzsáki,et al.  Hippocampal network patterns of activity in the mouse , 2003, Neuroscience.

[67]  Russell A. Epstein,et al.  The Occipital Place Area Is Causally Involved in Representing Environmental Boundaries during Navigation , 2016, Current Biology.

[68]  J E Lisman,et al.  Storage of 7 +/- 2 short-term memories in oscillatory subcycles , 1995, Science.

[69]  Arne D. Ekstrom,et al.  How and when the fMRI BOLD signal relates to underlying neural activity: The danger in dissociation , 2010, Brain Research Reviews.

[70]  Lin Tian,et al.  Functional imaging of hippocampal place cells at cellular resolution during virtual navigation , 2010, Nature Neuroscience.

[71]  Misun Kim,et al.  Multivoxel Pattern Analysis Reveals 3D Place Information in the Human Hippocampus , 2017, The Journal of Neuroscience.

[72]  A. Tort,et al.  Characterizing Speed Cells in the Rat Hippocampus. , 2018, Cell reports.

[73]  Arne D Ekstrom,et al.  Successful retrieval of competing spatial environments in humans involves hippocampal pattern separation mechanisms , 2015, eLife.

[74]  M. R. Mehta,et al.  Role of experience and oscillations in transforming a rate code into a temporal code , 2002, Nature.

[75]  May-Britt Moser,et al.  The entorhinal grid map is discretized , 2012, Nature.

[76]  Martin Fuhrmann,et al.  Locomotion, Theta Oscillations, and the Speed-Correlated Firing of Hippocampal Neurons Are Controlled by a Medial Septal Glutamatergic Circuit , 2015, Neuron.

[77]  Michael Frotscher,et al.  Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: A combined light and electron microscopic study , 1985, The Journal of comparative neurology.

[78]  Tobias Navarro Schröder,et al.  Hexadirectional coding of visual space in human entorhinal cortex , 2018, Nature Neuroscience.

[79]  Michael J. Kahana,et al.  Direct brain recordings fuel advances in cognitive electrophysiology , 2010, Trends in Cognitive Sciences.

[80]  Kathryn A Davis,et al.  Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum , 2017, The Journal of Neuroscience.

[81]  Zahra M. Aghajan,et al.  Theta Oscillations in the Human Medial Temporal Lobe during Real-World Ambulatory Movement , 2016, Current Biology.

[82]  J. Lisman,et al.  Heightened synaptic plasticity of hippocampal CA1 neurons during a Cholinergically induced rhythmic state , 1993, Nature.

[83]  Arne D. Ekstrom,et al.  A comparative study of human and rat hippocampal low‐frequency oscillations during spatial navigation , 2013, Hippocampus.

[84]  P. König,et al.  A comparison of hemodynamic and neural responses in cat visual cortex using complex stimuli. , 2004, Cerebral cortex.

[85]  Y. Sakurai,et al.  Theta oscillation and neuronal activity in rat hippocampus are involved in temporal discrimination of time in seconds , 2015, Front. Syst. Neurosci..

[86]  Bryan C. Souza,et al.  Asymmetry of the temporal code for space by hippocampal place cells , 2016, bioRxiv.

[87]  Arne D. Ekstrom,et al.  Human hippocampal theta activity during virtual navigation , 2005, Hippocampus.

[88]  M. Brecht,et al.  Pyramidal and Stellate Cell Specificity of Grid and Border Representations in Layer 2 of Medial Entorhinal Cortex , 2014, Neuron.

[89]  Michael A. DiSano,et al.  Variability of the Relationship between Electrophysiology and BOLD-fMRI across Cortical Regions in Humans , 2011, The Journal of Neuroscience.

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

[91]  Jeremy R. Manning,et al.  Broadband Shifts in Local Field Potential Power Spectra Are Correlated with Single-Neuron Spiking in Humans , 2009, The Journal of Neuroscience.

[92]  D. Hassabis,et al.  A Goal Direction Signal in the Human Entorhinal/Subicular Region , 2015, Current Biology.

[93]  Peter Gärdenfors,et al.  Navigating cognition: Spatial codes for human thinking , 2018, Science.

[94]  H. Braak,et al.  Staging of alzheimer's disease-related neurofibrillary changes , 1995, Neurobiology of Aging.

[95]  G. Buzsáki,et al.  Forward and reverse hippocampal place-cell sequences during ripples , 2007, Nature Neuroscience.

[96]  Tobias Navarro Schröder,et al.  Behavior-dependent directional tuning in the human visual-navigation network , 2020, Nature Communications.

[97]  P Kahane,et al.  Intracranial EEG and human brain mapping , 2003, Journal of Physiology-Paris.

[98]  I. Fried,et al.  Direct recordings of grid-like neuronal activity in human spatial navigation , 2013, Nature Neuroscience.

[99]  G. Buzsáki Two-stage model of memory trace formation: A role for “noisy” brain states , 1989, Neuroscience.

[100]  Jack Ryan,et al.  The Occipital Place Area is causally involved in representing environmental boundaries during navigation. , 2015, Journal of vision.

[101]  G. Buzsáki,et al.  Neuronal Oscillations in Cortical Networks , 2004, Science.

[102]  Nachum Ulanovsky,et al.  Representation of Three-Dimensional Space in the Hippocampus of Flying Bats , 2013, Science.

[103]  Russell A. Epstein,et al.  Distances between Real-World Locations Are Represented in the Human Hippocampus , 2011, The Journal of Neuroscience.

[104]  J. O’Keefe,et al.  Boundary Vector Cells in the Subiculum of the Hippocampal Formation , 2009, The Journal of Neuroscience.

[105]  Bijan Pesaran,et al.  Investigating large-scale brain dynamics using field potential recordings: analysis and interpretation , 2018, Nature Neuroscience.

[106]  Nikos K. Logothetis,et al.  The effect of a serotonin-induced dissociation between spiking and perisynaptic activity on BOLD functional MRI , 2008, Proceedings of the National Academy of Sciences.

[107]  R. Knight,et al.  The Hippocampus and Entorhinal Cortex Encode the Path and Euclidean Distances to Goals during Navigation , 2014, Current Biology.

[108]  Kathryn A Davis,et al.  Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation , 2018, Nature Communications.

[109]  Itzhak Fried,et al.  Contrasting roles of neural firing rate and local field potentials in human memory , 2007, Hippocampus.

[110]  Christian F. Doeller,et al.  Evidence for grid cells in a human memory network , 2010, Nature.

[111]  D. Hassabis,et al.  Decoding Neuronal Ensembles in the Human Hippocampus , 2009, Current Biology.

[112]  Dmitriy Aronov,et al.  Mapping of a non-spatial dimension by the hippocampal/entorhinal circuit , 2017, Nature.

[113]  G. Buzsáki Theta Oscillations in the Hippocampus , 2002, Neuron.

[114]  Timothy P. McNamara,et al.  Bias in Human Path Integration Is Predicted by Properties of Grid Cells , 2015, Current Biology.

[115]  Joseph R. Madsen,et al.  Human theta oscillations exhibit task dependence during virtual maze navigation , 1999, Nature.

[116]  Christian F. Doeller,et al.  Entorhinal cortex minimises uncertainty for optimal behaviour , 2018, bioRxiv.

[117]  Russell A. Epstein,et al.  Human entorhinal cortex represents visual space using a boundary-anchored grid , 2017, Nature Neuroscience.

[118]  Timothy M. Ellmore,et al.  Frequency-specific electrocorticographic correlates of working memory delay period fMRI activity , 2011, NeuroImage.

[119]  Sean M. Polyn,et al.  Beyond mind-reading: multi-voxel pattern analysis of fMRI data , 2006, Trends in Cognitive Sciences.

[120]  Arthur Gretton,et al.  Inferring spike trains from local field potentials. , 2008, Journal of neurophysiology.

[121]  Pierre-Pascal Lenck-Santini,et al.  Speed modulation of hippocampal theta frequency correlates with spatial memory performance , 2013, Hippocampus.

[122]  J. O’Keefe,et al.  Phase relationship between hippocampal place units and the EEG theta rhythm , 1993, Hippocampus.

[123]  E. Kandel,et al.  Increased Attention to Spatial Context Increases Both Place Field Stability and Spatial Memory , 2004, Neuron.

[124]  Christian F. Doeller,et al.  The Hippocampus Encodes Distances in Multidimensional Feature Space , 2019, Current Biology.

[125]  C. Koch,et al.  The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes , 2012, Nature Reviews Neuroscience.

[126]  Timothy E. J. Behrens,et al.  Organizing conceptual knowledge in humans with a gridlike code , 2016, Science.

[127]  Andrew J. Watrous,et al.  More than Spikes: Common Oscillatory Mechanisms for Content Specific Neural Representations during Perception and Memory This Review Comes from a Themed Issue on Brain Rhythms and Dynamic Coordination Sciencedirect Independent Contributions of Lfp Power and Phase to Neural Representation Content-spe , 2022 .

[128]  Jill K. Leutgeb,et al.  Grid and Nongrid Cells in Medial Entorhinal Cortex Represent Spatial Location and Environmental Features with Complementary Coding Schemes , 2017, Neuron.

[129]  Mary Hegarty,et al.  The Human Retrosplenial Cortex and Thalamus Code Head Direction in a Global Reference Frame , 2016, The Journal of Neuroscience.

[130]  Charlotte N. Boccara,et al.  Grid cells in pre- and parasubiculum , 2010, Nature Neuroscience.

[131]  L. Colom,et al.  Characterization of medial septal glutamatergic neurons and their projection to the hippocampus , 2005, Synapse.

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

[133]  Nikolaus Kriegeskorte,et al.  Frontiers in Systems Neuroscience Systems Neuroscience , 2022 .

[134]  Hippocampus and related areas: What the place cell literature tells us about cognitive maps in rats and humans. , 2013 .

[135]  Oliver Baumann,et al.  Evidence against the Detectability of a Hippocampal Place Code Using Functional Magnetic Resonance Imaging , 2017, eNeuro.

[136]  J. O'Keefe,et al.  The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. , 1971, Brain research.

[137]  Thomas Wolbers,et al.  Compromised Grid-Cell-like Representations in Old Age as a Key Mechanism to Explain Age-Related Navigational Deficits , 2018, Current Biology.

[138]  Geoffrey M. Barrett,et al.  Tau Pathology Induces Excitatory Neuron Loss, Grid Cell Dysfunction, and Spatial Memory Deficits Reminiscent of Early Alzheimer’s Disease , 2017, Neuron.

[139]  J. Jacobs Hippocampal theta oscillations are slower in humans than in rodents: implications for models of spatial navigation and memory , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

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

[141]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[142]  Michael X. Cohen,et al.  Sustained Neural Activity Patterns during Working Memory in the Human Medial Temporal Lobe , 2007, The Journal of Neuroscience.

[143]  J. Winson Loss of hippocampal theta rhythm results in spatial memory deficit in the rat. , 1978, Science.

[144]  R. Knight,et al.  The functional role of cross-frequency coupling , 2010, Trends in Cognitive Sciences.

[145]  Ashley N. Linder,et al.  The Spatial Periodicity of Grid Cells Is Not Sustained During Reduced Theta Oscillations , 2011, Science.

[146]  Arne D. Ekstrom,et al.  Oscillations Go the Distance: Low-Frequency Human Hippocampal Oscillations Code Spatial Distance in the Absence of Sensory Cues during Teleportation , 2016, Neuron.

[147]  T. Hafting,et al.  Microstructure of a spatial map in the entorhinal cortex , 2005, Nature.

[148]  Nathaniel J. Killian,et al.  A map of visual space in the primate entorhinal cortex , 2012, Nature.

[149]  J. Csicsvari,et al.  Theta phase–specific codes for two-dimensional position, trajectory and heading in the hippocampus , 2008, Nature Neuroscience.

[150]  Michael E. Hasselmo,et al.  Multiple Running Speed Signals in Medial Entorhinal Cortex , 2016, Neuron.

[151]  B. McNaughton,et al.  Independence of Firing Correlates of Anatomically Proximate Hippocampal Pyramidal Cells , 2001, The Journal of Neuroscience.

[152]  J. Lisman,et al.  Position reconstruction from an ensemble of hippocampal place cells: contribution of theta phase coding. , 2000, Journal of neurophysiology.

[153]  Hannah Monyer,et al.  Impaired path integration in mice with disrupted grid cell firing , 2017, Nature Neuroscience.

[154]  Valerie A. Carr,et al.  Prospective representation of navigational goals in the human hippocampus , 2016, Science.