Neural activity in human hippocampal formation reveals the spatial context of retrieved memories

Abstract

In many species, spatial navigation is supported by a network of place cells that exhibit increased firing whenever an animal is in a certain region of an environment. Does this neural representation of location form part of the spatiotemporal context into which episodic memories are encoded? We recorded medial temporal lobe neuronal activity as epilepsy patients performed a hybrid spatial and episodic memory task. We identified place-responsive cells active during virtual navigation and then asked whether the same cells activated during the subsequent recall of navigation-related memories without actual navigation. Place-responsive cell activity was reinstated during episodic memory retrieval. Neuronal firing during the retrieval of each memory was similar to the activity that represented the locations in the environment where the memory was initially encoded.

Fig. 1. The behavioral task

(A) Overhead map of the virtual environment. Red rectangles, store locations; blue squares, locations of nonstore buildings; green areas, grass and trees; small dark blue, brown, and yellow boxes; mailboxes, benches, and street lights. (B) An example storefront that a participant might encounter. (Translation of text at top left: “Please find the bakery.”) (C) The presentation of an item (a zucchini) upon arrival at the target store (bakery). (Translation of text at top left: “Successfully delivered: a zucchini.”) (D) The initiation of the recall period, as indicated by a black screen with asterisks.

Fig. 2. Place-responsive cells

(A) Firing-rate map for a cell responsive to northward traversals located in participant six’s hippocampus, shown separately for each cardinal direction. Gray represents all areas traversed by the participant, regardless of the direction of travel. (B) A cell responsive to eastward traversals recorded from participant one’s entorhinal cortex. (C) Regional distribution of place-responsive cells in the entire data set of 371 single units (H, hippocampus; A, amygdala; EC, entorhinal cortex; PHG, parahippocampal gyrus; Ant, anterior medial temporal lobe). The red dashed line indicates the false-positive rate of 5%. Asterisks denote brain regions where the number of place-responsive cells significantly exceeded chance levels.

Fig. 3. Spatial context reinstatement

(A) Time courses of neural similarity between ensemble place-cell activity during navigation and during item recall are shown for near, middle, and far spatial distance bins. Time courses, shown relative to recall onset, were computed in overlapping 500-ms windows (x values indicate the center of the window). Similarity is defined as the cosine of the angle between ensemble activity during recall and navigation, normalized as a rank score (). Shaded regions indicate SEM across recalled items. The horizontal bar indicates statistically significant time points, as determined by ANOVA with a false-discovery rate–adjusted significance threshold of 0.017. The vertical dotted line at 0 ms denotes the onset of the vocalization. (B) Average neural similarity for near, middle, and far spatial distance bins is shown for the time period of −300 to 700 ms relative to recall onset. Error bars indicate SEM across recalled items. (C) Neural similarity for near and far spatial distance bins for each of the included participants (thin colored lines) and the participant average (thick black line) is shown for the time period of −300 to 700 ms relative to recall onset. Error bars indicate SEM across participants.

Fig. 4. Place-responsive cell activity during navigation and recall

(Left) Navigation. “In Field” indicates the average place-responsive cell firing rate when navigating within a cell’s place field, whereas “Out Field” indicates the average place-responsive cell firing rate at locations outside of a place field (*P < 10⁻⁵). (Right) Recall. “Near” indicates the average place-responsive cell firing rate in the time period from 1.5 s before to 1 s after recall onset of items that were initially presented in or close to the center of a place field. In contrast, “Far” represents the average place-responsive cell firing rate in the same time window for recall of items that were initially presented far from the center of a place field (*P = 0.03). Error bars indicate SEM.