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How do we know where we are? Orientation in space is key to our daily existence as we follow familiar routes, navigate to a previous location, or just try to get home as quickly as possible. As well as being interesting in its own right, spatial cognition is also a useful model system in which to understand the neural bases of cognition and memory formation more generally. Spatial behavior offers potentially straightforward correlates of neuronal activity that can be studied similarly in adults and infants of both human and non-human animals. The neural mechanisms of spatial behavior can be realistically investigated in a well-controlled way with the aid of virtual reality technologies in humans and rodents. Virtual reality can thus help to bridge the gap between electrophysiological studies in rodents and brain imaging studies using functional magnetic resonance imaging in humans. Within this framework, this article aims to translate findings from the single cell level in rodents to understand the neural and systems level mechanisms of spatial cognition in the human brain. [ABSTRACT FROM PUBLISHER]

Episodic memories are constructed from sequences of events. When recalling such amemory, we not only recall individual events, but we also retrieve information about how the sequence of events unfolded.Here, we focus on the role of the hippocampal--entorhinal region in processing and remembering sequences of events, which are thought to be stored in relational networks. We summarize evidence that temporal relations are a central organizational principle formemories in the hippocampus. Importantly, we incorporate novel insights from recent studies about the role of the adjacent entorhinal cortex in sequence memory. In rodents, the lateral entorhinal subregion carries temporal information during ongoing behavior. The human homologue is recruited during memory recall where its representations reflect the temporal relationships between events encountered in a sequence. We further introduce the idea that the hippocampal--entorhinal region might enable temporal scaling of sequence representations. Flexible changes of sequence progression speed could underlie the traversal of episodic memories and mental simulations at different paces. In conclusion, we describe how the entorhinal cortex and hippocampus contribute to remembering event sequences--a core component of episodic memory. [ABSTRACT FROM AUTHOR]

The article comments on reports within the issue by researchers M. M. Yartsev and colleagues and J. G. Heys and team on the perception and neural coding of three-dimensional (3D) space in mammal brains, with particular focus on the mapping of place cell neurons in the hippocampus and grid cells in the medial entorhinal cortex. Yartsev and team looked at brain theta wave activity and 3D space encoding of hippocampal neurons of bats in flight. Heys and team compared theta rhythms of medial entorhinal cortex grid cells of bats and rats related to space coding.

A growing body of work is investigating the use of mental maps during decision-making. Here we discuss how decision-making organizes experiences according to an internal model of the current task, thereby structuring memory. Likewise, we consider how the structure of mental maps contributes to decision-making. [ABSTRACT FROM AUTHOR]

Functional neuroimaging studies have led to understanding the brain as a collection of spatially segregated functional networks. It is thought that each of these networks is in turn composed of a set of distinct sub-regions that together support each network's function. Considering the sub-regions to be an essential part of the brain's functional architecture, several strategies have been put forward that aim at identifying the functional sub-units of the brain by means of functional parcellations. Current parcellation strategies typically employ a bottom-up strategy, creating a parcellation by clustering smaller units. We propose a novel top-down parcellation strategy, using time courses of instantaneous connectivity to subdivide an initial region of interest into sub-regions. We use split-half reproducibility to choose the optimal number of sub-regions. We apply our Instantaneous Connectivity Parcellation (ICP) strategy on high-quality resting-state FMRI data, and demonstrate the ability to generate parcellations for thalamus, entorhinal cortex, motor cortex, and subcortex including brainstem and striatum. We evaluate the subdivisions against available cytoarchitecture maps to show that our parcellation strategy recovers biologically valid subdivisions that adhere to known cytoarchitectural features. [ABSTRACT FROM AUTHOR]

Anticipating the future is a key motif of the brain, possibly supported by mental simulation of upcoming events. Rodent single-cell recordings suggest the ability of spatially tuned cells to represent subsequent locations. Grid-like representations have been observed in the human entorhinal cortex during virtual and imagined navigation. However, hitherto it remains unknown if grid-like representations contribute to mental simulation in the absence of imagined movement. Participants imagined directions between building locations in a large-scale virtual-reality city while undergoing fMRI without re-exposure to the environment. Using multi-voxel pattern analysis, we provide evidence for representations of absolute imagined direction at a resolution of 30° in the parahippocampal gyrus, consistent with the head-direction system. Furthermore, we capitalize on the six-fold rotational symmetry of grid-cell firing to demonstrate a 60° periodic pattern-similarity structure in the entorhinal cortex. Our findings imply a role of the entorhinal grid-system in mental simulation and future thinking beyond spatial navigation. [ABSTRACT FROM AUTHOR]

The article presents a study that examines the human homologue of the rodent medial and lateral entorhinal cortex (MEC/LEC) in spatial navigation, memory and related disease.

The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected with presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected with distal CA1 and proximal subiculum (dCA1pSub) and lateral orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in the previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC. [ABSTRACT FROM AUTHOR]

Summary Grid cells are one of the core building blocks of spatial navigation [ 1 ]. Single-cell recordings of grid cells in the rodent entorhinal cortex revealed hexagonal coding of the local environment during spatial navigation [ 1 ]. Grid-like activity has also been identified in human single-cell recordings during virtual navigation [ 2 ]. Human fMRI studies further provide evidence that grid-like signals are also accessible on a macroscopic level [ 3–7 ]. Studies in both non-human primates [ 8 ] and humans [ 9, 10 ] suggest that grid-like coding in the entorhinal cortex generalizes beyond spatial navigation during locomotion, providing evidence for grid-like mapping of visual space during visual exploration—akin to the grid cell positional code in rodents during spatial navigation. However, electrophysiological correlates of the grid code in humans remain unknown. Here, we provide evidence for grid-like, hexadirectional coding of visual space by human high-frequency activity, based on two independent datasets: non-invasive magnetoencephalography (MEG) in healthy subjects and entorhinal intracranial electroencephalography (EEG) recordings in an epileptic patient. Both datasets consistently show a hexadirectional modulation of broadband high-frequency activity (60–120 Hz). Our findings provide first evidence for a grid-like MEG signal, indicating that the human entorhinal cortex codes visual space in a grid-like manner [ 8–10 ], and support the view that grid coding generalizes beyond environmental mapping during locomotion [ 4–6, 11 ]. Due to their millisecond accuracy, MEG recordings allow linking of grid-like activity to epochs during relevant behavior, thereby opening up the possibility for new MEG-based investigations of grid coding at high temporal resolution. Highlights • Hexadirectional modulation of human high-frequency electrophysiological activity • Grid-like mapping of visual space in the human entorhinal cortex • Grid-coding beyond environmental mapping during locomotion Staudigl et al. show grid-like modulation of human high-frequency activity in non-invasive magnetoencephalographic and intracranial EEG recordings. The results indicate that the human entorhinal cortex codes visual space in a grid-like manner, supporting the view that grid coding generalizes beyond environmental mapping during locomotion. [ABSTRACT FROM AUTHOR]