Mesoscopic Neural Representations in Spatial Navigation

doi:10.1016/j.tics.2019.04.011

Trends in Cognitive Sciences

Volume 23, Issue 7, July 2019, Pages 615-630

https://doi.org/10.1016/j.tics.2019.04.011 Get rights and content

Highlights

Neural representations of spatial navigation have mainly been studied at the microscopic level of single neurons or at the macroscopic level of fMRI.
Recent intracranial electroencephalography (iEEG) recordings in patients with epilepsy revealed neural representations of spatial features, including travelled distance, goal proximity to boundaries, and grid-like hexadirectional orientation. These representations occur at the mesoscopic level of brain oscillations, particularly in the theta frequency band.
Mesoscopic representations of space bridge the gap between their micro- and macroscopic counterparts. Experimentally testable scenarios may explain how the mesoscopic spatial representations relate to single-neuron firing, other neural oscillations, and fMRI signals.
Neural spatial representations may offer novel tools for biomarkers of neurological and psychiatric diseases.

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.

Section snippets

Towards a Multilevel Neural Code of Spatial Navigation

Spatial navigation is a core ability of most animals and humans [1]. Successful navigation requires highly specialized neural representations (see Glossary) that encode information about the shape and content of the environment, neural codes that reflect the location, direction, and speed of the navigating organism, and neural mechanisms that underlie goal-directed behavior within the environment. These spatial representations have been identified at various levels of brain organization ranging

Movement, Speed, Time, and Distance

Theta oscillations (Box 2) reliably appear during movement in the hippocampus of both rodents [17] and humans [18], although some characteristics of this signal differ between species. First, theta oscillations are more stable in rodents than in humans, in which theta oscillations occur in bursts of several cycles. Second, theta frequency may usually appear higher in rodents (4–10 Hz) than in humans (1–4 Hz) 19., 20., possibly because larger anatomical assemblies tend to synchronize at lower

Basic Relationships between Spiking Activity, LFPs, and BOLD

Although it is widely agreed that links between spiking activity, LFP power, and the BOLD signal exist (Figure 2), the details of these interrelations remain elusive. Here, we summarize what is currently known and propose that deepening this knowledge will boost our understanding of how spatial codes can coexist at multiple levels of brain organization.

Various studies of the relationship between LFP power and spiking activity revealed that spiking activity correlates positively with broadband

Behavioral and Clinical Relevance of Multilevel Spatial Representations

Having described how features of navigation and space relate to micro-, meso-, and macroscopic brain signals, examining their relevance for behavioral performance is important. At the microscopic level, experimentally induced shifts of place fields were associated with impaired spatial behavior [118], increased place field stability correlated with better task performance [119], and disrupting grid cell activity reduced the accuracy of path integration [67]. At the mesoscopic level, abolition

Concluding Remarks

Mesoscopic representations of space based on electrophysiological recordings in humans point towards a multilevel neural code for spatial navigation. These mesoscopic representations exhibit complex connections to spatial representations based on single neurons or on macroscopic fMRI patterns, and may yet mediate the relationship between these two other levels of brain organization. Thus, follow-up studies should further clarify the emergence of meso-/macroscopic spatial representations and

Outstanding Questions

Can we identify further types of mesoscopic representations of space, such as mesoscopic representations of head direction, borders, or 3D spatial information?
What is the brain-wide distribution of mesoscopic spatial representations, in particular of grid-like representations? Are mesoscopic spatial representations only observable in topographically organized brain regions?
What type of mesoscopic brain signals (which frequencies and which types of features) are causally most relevant for neural

Acknowledgments

L.K. was supported by the Federal Ministry of Education and Research (BMBF; 01GQ1705A), National Science Foundation (NSF) grant BCS-1724243, and National Institutes of Health (NIH) grant 563386. S.M. and J.J. were supported by NIH grants MH061975 and MH104606, and the NSF (BCS-1724243). L.W. was supported by the Strategic Priority Research Program of Chinese Academy of Science (XDB32010300), the Beijing Municipal Science and Technology Commission (Z171100000117014), CAS Interdisciplinary

Glossary

Allocentric reference frame: representation of the spatial environment with regard to features of the external world independent of the subject; typically contrasted with an egocentric reference frame that is centered on the subject.
Blood oxygen level-dependent (BOLD) signal: signal recorded using fMRI that, by measuring blood oxygenation in brain voxels, allows indirect conclusions about the neural activity underlying changes in blood oxygenation.
Frequency bands: canonical classes that summarize

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Cited by (38)

Grid codes underlie multiple cognitive maps in the human brain
2024, Progress in Neurobiology
Grid cells fire at multiple positions that organize the vertices of equilateral triangles tiling a 2D space and are well studied in rodents. The last decade witnessed rapid progress in two other research lines on grid codes—empirical studies on distributed human grid-like representations in physical and multiple non-physical spaces, and cognitive computational models addressing the function of grid cells based on principles of efficient and predictive coding. Here, we review the progress in these fields and integrate these lines into a systematic organization. We also discuss the coordinate mechanisms of grid codes in the human entorhinal cortex and medial prefrontal cortex and their role in neurological and psychiatric diseases.
Predictable navigation through spontaneous brain states with cognitive-map-like representations
2024, Progress in Neurobiology
Just as navigating a physical environment, navigating through the landscapes of spontaneous brain states may also require an internal cognitive map. Contemporary computation theories propose modeling a cognitive map from a reinforcement learning perspective and argue that the map would be predictive in nature, representing each state as its upcoming states. Here, we used resting-state fMRI to test the hypothesis that the spaces of spontaneously reoccurring brain states are cognitive map-like, and may exhibit future-oriented predictivity. We identified two discrete brain states of the navigation-related brain networks during rest. By combining pattern similarity and dimensional reduction analysis, we embedded the occurrences of each brain state in a two-dimensional space. Successor representation modeling analysis recognized that these brain state occurrences exhibit place cell-like representations, akin to those observed in a physical space. Moreover, we observed predictive transitions of reoccurring brain states, which strongly covaried with individual cognitive and emotional assessments. Our findings offer a novel perspective on the cognitive significance of spontaneous brain activity and support the theory of cognitive map as a unifying framework for mental navigation.
Goal-seeking compresses neural codes for space in the human hippocampus and orbitofrontal cortex
2023, Neuron
Humans can navigate flexibly to meet their goals. Here, we asked how the neural representation of allocentric space is distorted by goal-directed behavior. Participants navigated an agent to two successive goal locations in a grid world environment comprising four interlinked rooms, with a contextual cue indicating the conditional dependence of one goal location on another. Examining the neural geometry by which room and context were encoded in fMRI signals, we found that map-like representations of the environment emerged in both hippocampus and neocortex. Cognitive maps in hippocampus and orbitofrontal cortices were compressed so that locations cued as goals were coded together in neural state space, and these distortions predicted successful learning. This effect was captured by a computational model in which current and prospective locations are jointly encoded in a place code, providing a theory of how goals warp the neural representation of space in macroscopic neural signals.
MEG frequency tagging reveals a grid-like code during attentional movements
2023, Cell Reports
Grid-cells firing fields tile the environment with a 6-fold periodicity during both locomotion and visual exploration. Here, we tested, in humans, whether movements of covert attention elicit grid-like coding using frequency tagging. Participants observed visual trajectories presented sequentially at fixed rate, allowing different spatial periodicities (e.g., 4-, 6-, and 8-fold) to have corresponding temporal periodicities (e.g., 1, 1.5, and 2 Hz), thus resulting in distinct spectral responses. We found a higher response for the (grid-like) 6-fold periodicity and localized this effect in medial-temporal sources. In a control experiment featuring the same temporal periodicity but lacking spatial structure, the 6-fold effect did not emerge, suggesting its dependency on spatial movements of attention. We report evidence that grid-like signals in the human medial-temporal lobe can be elicited by covert attentional movements and suggest that attentional coding may provide a suitable mechanism to support the activation of cognitive maps during conceptual navigation.
Multi-scale goal distance representations in human hippocampus during virtual spatial navigation
2023, Current Biology
Goal-directed navigation relies on both coarse and fine-grained coding of spatial distance between the current position of a navigating subject and a goal destination. However, the neural signatures underlying goal distance coding remain poorly understood. Using intracranial EEG recordings from the hippocampus of drug-resistant epilepsy patients who performed a virtual spatial navigation task, we found that the right hippocampal theta power was significantly modulated by goal distance and decreased with goal proximity. This modulation varied along the hippocampal longitudinal axis such that theta power in the posterior hippocampus decreased more strongly with goal proximity. Similarly, neural timescale, reflecting the duration across which information can be maintained, increased gradually from the posterior to anterior hippocampus. Taken together, this study provides empirical evidence for multi-scale spatial representations of goal distance in the human hippocampus and links the hippocampal processing of spatial information to its intrinsic temporal dynamics.
Neural activity during monkey vehicular wayfinding
2023, Journal of the Neurological Sciences
Navigation gets us from place to place, creating a path to arrive at a goal. We trained a monkey to steer a motorized cart in a large room, beginning at its trial-by-trial start location and ending at a trial-by-trial cued goal location. While the monkey steered its autonomously chosen path to its goal, we recorded neural activity simultaneously in both the hippocampus (HPC) and medial superior temporal (MST) cortex.
Local field potentials (LFPs) in these sites show similar patterns of activity with the 15–30 Hz band highlighting specific room locations. In contrast, 30–100 Hz LFPs support a unified map of the behaviorally relevant start and goal locations. The single neuron responses (SNRs) do not substantially contribute to room or start-goal maps. Rather, the SNRs form a continuum from neurons that are most active when the monkey is moving on a path toward the goal, versus other neurons that are most active when the monkey deviates from paths toward the goal.
Granger analyses suggest that HPC firing precedes MST firing during cueing at the trial start location, mainly mediated by off-path neurons. In contrast, MST precedes HPC firing during steering, mainly mediated by on-path neurons. Interactions between MST and HPC are mediated by the parallel activation of on-path and off-path neurons, selectively activated across stages of this wayfinding task.

View all citing articles on Scopus

⁷: These authors contributed equally to this work.

⁸: These authors contributed equally to this work.

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Trends in Cognitive Sciences

ReviewMesoscopic Neural Representations in Spatial Navigation

Highlights

Section snippets

Towards a Multilevel Neural Code of Spatial Navigation

Movement, Speed, Time, and Distance

Basic Relationships between Spiking Activity, LFPs, and BOLD

Behavioral and Clinical Relevance of Multilevel Spatial Representations

Concluding Remarks

Outstanding Questions

Acknowledgments

Glossary

Neuron

Brain Res.

Curr. Biol.

Neuropsychologia

Neuron

Neuroscience

Trends Cogn. Sci.

Curr. Opin. Neurobiol.

Brain Res.

Cell Rep.

Neuron

Neuron

Neuron

Neuron

Neuroimage

Neuron

Trends Neurosci.

Curr. Biol.

Curr. Biol.

Neuron

Curr. Biol.

Neuron

Curr. Biol.

Brain Res. Rev.

Brain Res.

Neuron

Cellular networks underlying human spatial navigation

Nature

Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis

J. Neurosci.

Representation of geometric borders in the entorhinal cortex

Science

Microstructure of a spatial map in the entorhinal cortex

Nature

Direct recordings of grid-like neuronal activity in human spatial navigation

Nat. Neurosci.

Prospective representation of navigational goals in the human hippocampus

Science

Successful retrieval of competing spatial environments in humans involves hippocampal pattern separation mechanisms

eLife

Anchoring the neural compass: coding of local spatial reference frames in human medial parietal lobe

Nat. Neurosci.

The human retrosplenial cortex and thalamus code head direction in a global reference frame

J. Neurosci.

Evidence for grid cells in a human memory network

Nature

Reduced grid-cell-like representations in adults at genetic risk for Alzheimer’s disease

Science

Compromised grid-cell-like representations in old age as a key mechanism to explain age-related navigational deficits

Curr. Biol.

Human hippocampal theta activity during virtual navigation

Hippocampus

A comparative study of human and rat hippocampal low-frequency oscillations during spatial navigation

Hippocampus

Hippocampal theta oscillations are slower in humans than in rodents: implications for models of spatial navigation and memory

Philos. Trans. R. Soc. B Biol. Sci.

Neuronal oscillations in cortical networks

Science

Low-frequency theta oscillations in the human hippocampus during real-world and virtual navigation

Nat. Commun.

Theta oscillations in the human medial temporal lobe during real-world ambulatory movement

Curr. Biol.

Functionally distinct high and low theta oscillations in the human hippocampus

bioRxiv

Right-lateralized brain oscillations in human spatial navigation

J. Cogn. Neurosci.

Frequency of gamma oscillations routes flow of information in the hippocampus

Nature

Review
Mesoscopic Neural Representations in Spatial Navigation