Hippocampal Neuronal Activity Preceding Stimulus Predicts Later Memory Success

Word memory tasks. a, Example of the timeline of the visual item memory task and (b) associative memory task. Memory tasks comprised three successive stages encoding, distractor, and retrieval. Each patient sequentially completed words items during encoding, which was followed by a white fixation cue with a black screen for 1 s. The green dashed line box indicates the preceding stimulus interval.

Numbers of neurons and mean firing rates from different brain areas. a, Units’ numbers from each brain area were as follows, from left to right: 20, 10, and 2. b, The mean firing rates of units, respectively. All units are included, regardless of firing rates. The mean firing rates of the hippocampal and amygdala are 1.71 and 1.47, respectively. Error bars are ±SEM. RH, right hippocampus; LH, left hippocampus; RA, the right amygdala.

Group-level comparison of spiking activity in the hippocampus during an item memory task. a, The mean firing rates across neurons (n = 11) during resting states versus memory encoding showed a significant increase in firing rates for memory encoding compared with resting states (Wilcoxon signed-rank test, ***p < 0.001). b, Group-level comparison of pre-SME and during-SME hippocampal mean firing rates. During the preceding stimulus, hippocampal firing rates were higher for subsequent remembered than forgotten words (left, Wilcoxon signed-rank test, **p < 0.01). However, the trend during-SME hippocampal activity was not significant (right, Wilcoxon signed-rank test, p = 0.058). c, Pre-SME and during-SME mean firing rates for an operation of words subsequently remembered (left) versus forgotten (right). The difference between pre-SME and during-SME was not significant in both remembered and forgotten words (Wilcoxon signed-rank test, p = 0.0518, p = 0.082, respectively).

Hippocampal neuronal responses to subsequently remembered and forgotten word items. Shown are representative examples of hippocampal neurons that significantly increase firing rates across trials. Preceding stimulus and during-stimulus raster plot of firing rates during encoding sessions. The red lines mark stimulus onset at 0; the offset is at 3 s (x-axis). Raster rows represent single trials, and each dot represents an action potential. Next, the preceding stimulus and during-stimulus raster plot of firing rates for the remembered and forgotten conditions during encoding (**p < 0.01, *p < 0.05, permutation-based p-value).

Hippocampal neuronal responses to subsequently remembered and forgotten word items. a, The mean firing rates between resting states and encoding. Mean firing rates for the encoding duration are significantly higher than the resting state. b, The hippocampal preceding stimulus neuronal activity (pre-SME) is significantly higher in subsequently remembered items compared with subsequently forgotten items (***p < 0.001, *p < 0.05, permutation-based p-value). This neuron was selective to only preceding stimulus with similar increases in activity in the during-stimulus condition. c, The hippocampal spiking activity indicated the difference between preceding stimulus and during-stimulus activity was negligible in both remembered and forgotten conditions (n.s., p = 0.0524, respectively, permutation-based p-value). n.s. indicates not significant.