Spatially Periodic Computation in the Entorhinal-Hippocampal Circuit During Navigation
Curation statements for this article:-
Curated by eLife
eLife Assessment
This study provides valuable results on how entorhinal and hippocampal activity may support human thinking in perceptual spaces. It replicates the hexagonal symmetry of fMRI activity in the entorhinal cortex, reports novel findings on 3-fold symmetry in both behavioral performance and hippocampal fMRI activity, and links these results within a computational model. However, the methods – while potentially creative and interesting – are not fully justified or explained, and the conclusions remain incomplete. With further explanation, justification, and interpretation, this work could represent a significant step forward in understanding how cognitive maps are utilized.
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (eLife)
Abstract
To achieve the computational goal of navigating in both physical and mental spaces, the human brain employs a cognitive map constructed by the global metrics of the entorhinal cortex and the local locations of the hippocampus. However, the mechanism by which these two areas interact to support navigation remains unclear. Here, we designed an object-matching task where human participants unknowingly manipulated object variants arranged in a ring-like structure around a central prototype. Functional MRI revealed a 3- fold spatial periodicity of hippocampal activity, which tracked the navigation trajectories from the original object variants to the central prototype in the object space. Importantly, this spatial periodicity of the hippocampus was phase-locked with the well-documented 6-fold periodicity of the entorhinal cortex, suggesting a periodic mechanism connecting these two areas. In addition, the 3-fold periodicity was replicated in human behavior, which varied with a function of spatial directions and phase-locked with hippocampal activity. Finally, we proposed an EC-HPC PhaseSync model, illustrating a framework of the hippocampal-entorhinal network, in which the 6-fold spatial periodicity of entorhinal grid cell populations embeds vector fields that are represented in the hippocampus for conceptual navigation.
Article activity feed
-
eLife Assessment
This study provides valuable results on how entorhinal and hippocampal activity may support human thinking in perceptual spaces. It replicates the hexagonal symmetry of fMRI activity in the entorhinal cortex, reports novel findings on 3-fold symmetry in both behavioral performance and hippocampal fMRI activity, and links these results within a computational model. However, the methods – while potentially creative and interesting – are not fully justified or explained, and the conclusions remain incomplete. With further explanation, justification, and interpretation, this work could represent a significant step forward in understanding how cognitive maps are utilized.
-
Reviewer #1 (Public review):
Summary:
Zhang and colleagues examine neural representations underlying abstract navigation in the entorhinal cortex (EC) and hippocampus (HC) using fMRI. This paper replicates a previously identified hexagonal modulation of abstract navigation vectors in abstract space in EC in a novel task involving navigating in a conceptual Greeble space. In HC, the authors claim to identify a three-fold signal of the navigation angle. They also use a novel analysis technique (spectral analysis) to look at spatial patterns in these two areas and identify phase coupling between HC and EC. Finally, the authors propose an EC-HPC PhaseSync Model to understand how the EC and HC construct cognitive maps. While the wide array of techniques used is impressive and their creativity in analysis is admirable, overall, I found the …
Reviewer #1 (Public review):
Summary:
Zhang and colleagues examine neural representations underlying abstract navigation in the entorhinal cortex (EC) and hippocampus (HC) using fMRI. This paper replicates a previously identified hexagonal modulation of abstract navigation vectors in abstract space in EC in a novel task involving navigating in a conceptual Greeble space. In HC, the authors claim to identify a three-fold signal of the navigation angle. They also use a novel analysis technique (spectral analysis) to look at spatial patterns in these two areas and identify phase coupling between HC and EC. Finally, the authors propose an EC-HPC PhaseSync Model to understand how the EC and HC construct cognitive maps. While the wide array of techniques used is impressive and their creativity in analysis is admirable, overall, I found the paper a bit confusing and unconvincing. I recommend a significant rewrite of their paper to motivate their methods and clarify what they actually did and why. The claim of three-fold modulation in HC, while potentially highly interesting to the community, needs more background to motivate why they did the analysis in the first place, more interpretation as to why this would emerge in biology, and more care taken to consider alternative hypotheses seeped in existing models of HC function. I think this paper does have potential to be interesting and impactful, but I would like to see these issues improved first.
General comments:
(1) Some of the terminology used does not match the terminology used in previous relevant literature (e.g., sinusoidal analysis, 1D directional domain).
(2) Throughout the paper, novel methods and ideas are introduced without adequate explanation (e.g., the spectral analysis and three-fold periodicity of HC).
-
Reviewer #2 (Public review):
The authors report results from behavioral data, fMRI recordings, and computer simulations during a conceptual navigation task. They report 3-fold symmetry in behavioral and simulated model performance, 3-fold symmetry in hippocampal activity, and 6-fold symmetry in entorhinal activity (all as a function of movement directions in conceptual space). The analyses are thoroughly done, and the results and simulations are very interesting.
-
Author response:
Reviewer #1, Comment (1): Terminology
We fully acknowledge the importance of terminological consistency and will align our usage with established literature. Specifically, we will revise as follows,
(1) Replace “sinusoidal analysis” with either “sinusoidal modulation” (Doeller et al., 2010; Bao et al., 2019; Raithel et al., 2023) or “GLM with sinusoidal (cos/sin) regressors” (Constantinescu et al., 2016).
(2) Replace “1D directional domain” with either “angular domain of movement directions (0–360°)” or “directional modulation analysis”.
Reviewer #1, Comment (2): Spectral analysis and 3-fold periodicity
We agree that the presentation of our spectral analysis and the theoretical motivation underlying our expectation of a three-fold periodicity within hippocampal data requires further clarification.
In our revised …
Author response:
Reviewer #1, Comment (1): Terminology
We fully acknowledge the importance of terminological consistency and will align our usage with established literature. Specifically, we will revise as follows,
(1) Replace “sinusoidal analysis” with either “sinusoidal modulation” (Doeller et al., 2010; Bao et al., 2019; Raithel et al., 2023) or “GLM with sinusoidal (cos/sin) regressors” (Constantinescu et al., 2016).
(2) Replace “1D directional domain” with either “angular domain of movement directions (0–360°)” or “directional modulation analysis”.
Reviewer #1, Comment (2): Spectral analysis and 3-fold periodicity
We agree that the presentation of our spectral analysis and the theoretical motivation underlying our expectation of a three-fold periodicity within hippocampal data requires further clarification.
In our revised manuscript, we will:
(1) Clearly articulate the theoretical motivation for anticipating a three-fold signal, explicitly linking it to the known hexagonal grid structure encoded by the entorhinal cortex.(2) Clarify our methodological rationale for using Fourier analysis (FFT).
a) FFT allows unbiased exploration of multiple candidate periodicities (e.g., 3–7-fold) without predefined assumptions.
b) FFT results cross-validate our sinusoidal modulation results, providing complementary evidence supporting the 6-fold periodicity in EC and 3-fold periodicity in HPC.
c) FFT uniquely facilitates analysis of periodicities in behavioral performance data, which is not feasible via standard sinusoidal GLM approaches. This consistency allows us to directly compare periodicities across neural and behavioral data.
(3) Further, we will expand our discussion to provide:
a) A deeper interpretation of potential biological bases for the observed hippocampal three-fold periodicity.
b) A careful examination of alternative explanations within existing hippocampal modeling frameworks.
Reference:
Doeller, C. F., Barry, C., & Burgess, N. (2010). Evidence for grid cells in a human memory network. Nature, 463(7281), 657-661.
Constantinescu, A. O., O'Reilly, J. X., & Behrens, T. E. J. (2016). Organizing conceptual knowledge in humans with a gridlike code. Science, 352(6292), 1464-1468.
Bao, X., Gjorgieva, E., Shanahan, L. K., Howard, J. D., Kahnt, T., & Gottfried, J. A. (2019). Grid-like neural representations support olfactory navigation of a two-dimensional odor space. Neuron, 102(5), 1066-1075.
Raithel, C. U., Miller, A. J., Epstein, R. A., Kahnt, T., & Gottfried, J. A. (2023). Recruitment of grid-like responses in human entorhinal and piriform cortices by odor landmark-based navigation. Current Biology, 33(17), 3561-3570
-
