A dissociation of encoding and retrieval processes in the human hippocampus

Abstract

The hippocampal formation performs two related but distinct memory functions: encoding of novel information and retrieval of episodes. Little evidence, however, resolves how these two processes are implemented within the same anatomical structure. Here we use high-resolution functional magnetic resonance imaging to show that distinct subregions of the hippocampus are differentially involved in encoding and retrieval. We found that regions early in the hippocampal circuit (dentate gyrus and CA fields 2 and 3) were selectively active during episodic memory formation, whereas a region later in the circuit (the subiculum) was active during the recollection of the learning episode. Different components of the hippocampal circuit likely contribute to different degrees to the two basic memory functions.

Figure 1.

a, Sample of the encoding (top) and retrieval (bottom) stimuli and the timing of events within each trial. The color and orientation of the picture pairs varied on each trial and were used to assess recollection in the posttest phase. b, Results from the posttest. Chance refers to the probability of guessing correctly for color (4 possible choices) or orientation (2 possible choices). c, A sample slice prescription. The slices illustrate the in-plane images that were selected for functional imaging.

Figure 2.

Averaged event-related responses in anatomically defined hippocampal regions from nine subjects sorted according to R-K performance during the retrieval phase. The right panels show estimated response amplitudes for each memory type measured by fitting model responses to the data. Amplitude and time course units are both percentage change of the fMRI signal from baseline, and error bars represent ±1 SE between subjects. R, Red lines; K, blue lines; F, cyan lines; CR, green lines.

Figure 3.

Averaged event-related responses in anatomically defined extrahippocampal regions from nine subjects sorted according to R-K performance during the retrieval phase. Plotting conventions are as in Figure 2. PHC, Parahippocampal cortex.

Figure 4.

Averaged encoding event-related responses from nine subjects sorted according to whether items would later be labeled as R or K during the retrieval phase. The left panels plot the difference time courses created by subtracting the forgotten responses from the R and K responses. This subtraction was performed to remove the late activity and reveal potential differences between conditions in the early part of the trial. R, Red lines; K, blue lines. The right panels plot estimated response amplitudes from the difference time courses.

Figure 5.

Averaged event-related responses in anatomically defined extrahippocampal regions from nine subjects sorted according to R-K performance during the encoding phase. Because late peaks do not dominate as in the hippocampus, simple average time courses are plotted and were used to estimate response amplitudes (not difference time courses as in Fig. 4). Plotting conventions are as in Figure 2.