High-resolution fMRI of content-sensitive subsequent memory responses in human medial temporal lobe

Abstract

The essential role of the medial temporal lobe (MTL) in long-term memory for individual events is well established, yet important questions remain regarding the mnemonic functions of the component structures that constitute the region. Within the hippocampus, recent functional neuroimaging findings suggest that formation of new memories depends on the dentate gyrus and the CA(3) field, whereas the contribution of the subiculum may be limited to retrieval. During encoding, it has been further hypothesized that structures within MTL cortex contribute to encoding in a content-sensitive manner, whereas hippocampal structures may contribute to encoding in a more domain-general manner. In the current experiment, high-resolution fMRI techniques were utilized to assess novelty and subsequent memory effects in MTL subregions for two classes of stimuli--faces and scenes. During scanning, participants performed an incidental encoding (target detection) task with novel and repeated faces and scenes. Subsequent recognition memory was indexed for the novel stimuli encountered during scanning. Analyses revealed voxels sensitive to both novel faces and novel scenes in all MTL regions. However, similar percentages of voxels were sensitive to novel faces and scenes in perirhinal cortex, entorhinal cortex, and a combined region comprising the dentate gyrus, CA(2), and CA(3), whereas parahippocampal cortex, CA(1), and subiculum demonstrated greater sensitivity to novel scene stimuli. Paralleling these findings, subsequent memory effects in perirhinal cortex were observed for both faces and scenes, with the magnitude of encoding activation being related to later memory strength, as indexed by a graded response tracking recognition confidence, whereas subsequent memory effects were scene-selective in parahippocampal cortex. Within the hippocampus, encoding activation in the subiculum correlated with subsequent memory for both stimulus classes, with the magnitude of encoding activation varying in a graded manner with later memory strength. Collectively, these findings suggest a gradient of content sensitivity from posterior (parahippocampal) to anterior (perirhinal) MTL cortex, with MTL cortical regions differentially contributing to successful encoding based on event content. In contrast to recent suggestions, the present data further indicate that the subiculum may contribute to successful encoding irrespective of event content.

Figure 1

Materials and task design. (A) The scanned encoding task required participants to perform target detection on novel and repeated face and scene stimuli. (B) During an unscanned recognition memory task, participants viewed the novel stimuli from the target detection task as well as unstudied faces and scenes. Participants provided recognition responses based on a 5-point scale (1 = absolutely sure an item was new, 2 = somewhat sure an item was new, 3 = very unsure an item was old or new, 4 = somewhat sure an item was old, and 5 = absolutely sure an item was old).

Figure 2

Behavioral performance. (A) Target detection accuracy during scanned encoding for novel (dark gray), repeated (light gray), and target (white) stimuli. (B) Percentage of “old” responses on the recognition memory task collapsed across confidence for face and scene stimuli. Hits (green) and false alarms (white) are plotted separately for each stimulus class. (C) Percentage of responses on the recognition memory task for old and new items by level of confidence for face and scene stimuli. High-confidence “old” responses (dark green), low-confidence “old” responses (light green), “unsure” responses (yellow), low-confidence “new” responses (dark gray), and high-confidence “new” responses (light gray) are plotted separately for each stimulus class.

Figure 3

Encoding activation in anatomically defined MTL cortical regions based on subsequent memory. Percent signal change in perirhinal, parahippocampal, and entorhinal cortices is plotted for stimuli recognized with high confidence (dark green), stimuli recognized with low confidence (light green), forgotten (dark gray), and repeated (white) stimuli for faces and scenes.

Figure 4

(A) MTL novelty responses sensitive to stimulus content displayed for five individual participants. Voxels sensitive to face (red), scene (yellow), and both face and scene (orange) novelty are displayed along the anterior–posterior axis of the MTL. The region of the parahippocampal gyrus depicted in the two most anterior slices corresponds to perirhinal cortex, whereas the region of the parahippocampal gyrus depicted in the two most posterior slices corresponds to parahippocampal cortex. (B) Pattern of content sensitivity in anatomically defined MTL cortical regions. For voxels demonstrating sensitivity to novel stimuli relative to baseline, the percentage of novelty-sensitive voxels response to faces (red), scenes (yellow), and both classes of stimuli (orange) are plotted for perirhinal, parahippocampal, and entorhinal cortices, and similarly in (C) for the hippocampal subfields (CA_2,3/DG, CA₁, and subiculum). The mean number of content-sensitive voxels within a region is represented in the upper right-hand corner of the graph for each ROI.

Figure 5

Encoding activation in content-sensitive (A) face and (B) scene voxels based on subsequent memory. Percent signal change in perirhinal and parahippocampal cortices as well as the subiculum is plotted for stimuli recognized with high confidence (dark green), stimuli recognized with low confidence (light green), forgotten (dark gray), and repeated (white) stimuli for faces and scenes. Asterisks indicated a significant linear trend across subsequent memory performance for novel stimuli. (C) Peristimulus time courses averaged across face- and scene-sensitive voxels in functionally defined ROIs for face and scene stimuli recognized with high confidence (dark green), stimuli recognized with low confidence (light green), forgotten (black), and repeated (gray).