Spatial Representations in the Human Brain

Abstract

While extensive research on the neurophysiology of spatial memory has been carried out in rodents, memory research in humans had traditionally focused on more abstract, language-based tasks. Recent studies have begun to address this gap using virtual navigation tasks in combination with electrophysiological recordings in humans. These studies suggest that the human medial temporal lobe (MTL) is equipped with a population of place and grid cells similar to that previously observed in the rodent brain. Furthermore, theta oscillations have been linked to spatial navigation and, more specifically, to the encoding and retrieval of spatial information. While some studies suggest a single navigational theta rhythm which is of lower frequency in humans than rodents, other studies advocate for the existence of two functionally distinct delta-theta frequency bands involved in both spatial and episodic memory. Despite the general consensus between rodent and human electrophysiology, behavioral work in humans does not unequivocally support the use of a metric Euclidean map for navigation. Formal models of navigational behavior, which specifically consider the spatial scale of the environment and complementary learning mechanisms, may help to better understand different navigational strategies and their neurophysiological mechanisms. Finally, the functional overlap of spatial and declarative memory in the MTL calls for a unified theory of MTL function. Such a theory will critically rely upon linking task-related phenomena at multiple temporal and spatial scales. Understanding how single cell responses relate to ongoing theta oscillations during both the encoding and retrieval of spatial and non-spatial associations appears to be key toward developing a more mechanistic understanding of memory processes in the MTL.

Keywords: MTL; cognitive map; episodic memory; grid cells; navigation; place cells; spatial memory; theta.

FIGURE 1

Place and grid cell activity in humans. (A) Traveled path (left) and firing rate map of an exemplary place cell (right) in a city block environment. Adapted with permission (Ekstrom et al., 2003) from Springer Nature. (B) City environment (left) and firing rate map for an exemplary unidirectional place cell firing only during northward traversals (right). Adapted with permission (Miller et al., 2013) from Science. (C) Open-field environment (top), firing rate map (lower left), and spatial autocorrelation function (lower right) of an exemplary grid cell. Adapted with permission (Jacobs et al., 2013) from Springer Nature. (D) Small (left) and large (right) virtual arena with corresponding autocorrelation functions showing small and large grid spacing, respectively. Adapted with permission (Nadasdy et al., 2017) from PNAS. (E) Percentage of place- and grid-responsive cells in the entorhinal cortex (EC), hippocampus (HC), parahippocampal gyrus (PHG), amygdala (A), cingulate cortex (CC), and frontal cortex (FC). Data were summarized from Ekstrom et al. (2003); Jacobs et al. (2013), Miller et al. (2013), and Nadasdy et al. (2017). Standard error of the mean is shown if more than one of the studies reported data for a given brain region.

FIGURE 2

Evidence for grid-cells in fMRI BOLD. (A) Rationale for observing grid-like activity in BOLD contrast. Based on the assumption that grid cells show a similar grid orientation across the population, movement in a direction aligned with the common grid direction should be associated with higher firing rates across the population and therefore higher BOLD signal than movement in a direction misaligned with the grid. Underlying autocorrelation function adapted with permission (Jacobs et al., 2013) from Springer Nature. (B) During virtual navigation, movement in a direction aligned with grid orientation, which was estimated from an independent subset of the data, resulted in higher BOLD in the entorhinal cortex than movement in a direction misaligned with the grid. Data from Doeller et al. (2010). (C) Analogously, eye movements in a direction aligned with grid orientation in a visual tracking task are associated with higher BOLD than eye movements in a direction misaligned with the grid. Data from Nau et al. (2018).

FIGURE 3

Theta oscillations during virtual navigation. (A) The predominant frequency of oscillations occurring during virtual navigation appears to be lower in humans than rats. A clear peak around 8 Hz is evident in rats, while human data shows a peak around 3–4 Hz. Adapted with permission (Watrous et al., 2013a) from Wiley Periodicals. (B) Theta oscillations are evident in the power spectrum during movement onset (top), the remainder of the movement period (middle), and the full movement period (bottom) in two distinct frequency bands around 3–4 and 8–9 Hz, at the edges of the conventional theta rhythm. Theta oscillations are of higher amplitude during long compared to short paths (bottom).

FIGURE 4

Key regions involved in spatial memory and navigation. The PPC, situated along the dorsal visual stream, extracts spatial coordinates from visual input and translates between different egocentric reference frames (e.g., retinotopic or head-centered). These can be used to track motion and plan movements in coordination with the PFC. The PHC receives input not only via the ventral visual pathway but also from the dorsal pathway via the RSC. It projects to the HC via the EC, where allocentric coding pre-dominates. The RSC might translate between parietal egocentric and medial temporal allocentric representations. Prefrontal interactions with HC and surrounding MTL may facilitate goal-directed navigation. EC, entorhinal cortex; HC, hippocampus; MTL, medial temporal lobel; PHC, parahippocampal cortex; PPC, posterior parietal cortex; RSC, retrosplenial cortex; VC, visual cortex.

FIGURE 5

Cells in the human MTL code non-spatial features as well as spatial features outside their respective spatial context. (A) While viewing a black screen, the activity of place cells is reinstated when subjects recall words that were encoded inside the cells’ place field in a virtual city environment. This effect is evident at the population (left) and individual cell (right) level. Adapted with permission (Miller et al., 2013) from Science. (B) Goal- and view- responsive cells in the hippocampus (HC), parahippocampal gyrus (PHG), amygdala (A), and frontal cortex (FC). Dark turquoise bars indicate responsiveness to stores and light turquoise bars indicate responsiveness to both stores and passengers. Adapted with permission (Ekstrom et al., 2003) from Springer Nature. (C) Evidence from fMRI suggests that cells in the entorhinal cortex show grid-like activity that codes position in a conceptual space representing visual features of birds (neck length and leg length). BOLD contrast was higher for viewing or imagining morphing trajectories that were aligned with the common grid orientation as compared with misaligned trajectories. Data from Constantinescu et al. (2016).

FIGURE 6

Theta oscillations in episodic memory formation and retrieval. (A) Model suggesting a common role for hippocampal theta oscillations and phase precession in memory for spatial and non-spatial sequences (e.g., during navigation or a list-learning task; Buzsáki, 2005). Successive firing of hippocampal cells within a theta cycle establishes temporal associations between both place and item representations through synaptic plasticity, which favors associations in the forward direction. Multiple encounters of the same items/places in different serial order establishes semantic/allocentric representations of conceptual and physical space. In part adapted with permission (Buzsáki, 2005) from Wiley Periodicals. (B) Hippocampal electrodes showing theta oscillations around 3–4 and 8–9 Hz, analogously to theta effects during navigation (see Figure 3B; left), as well as positive and negative subsequent memory effects (SME; right). Positive SMEs predominate around 3–4 Hz. Adapted with permission (Lega et al., 2012) from Wiley Periodicals.