Predictability matters: role of the hippocampus and prefrontal cortex in disambiguation of overlapping sequences

Abstract

Previous research has demonstrated that areas in the medial temporal lobe and prefrontal cortex (PFC) show increased activation during retrieval of overlapping sequences. In this study, we designed a task in which degree of overlap varied between conditions in order to parse out the contributions of hippocampal and prefrontal subregions as overlap between associations increased. In the task, participants learned sequential associations consisting of a picture frame, a face within the picture frame, and an outdoor scene. The control condition consisted of a single frame-face-scene sequence. In the low overlap condition, each frame was paired with two faces and two scenes. In the high overlap condition, each frame was paired with four faces and four scenes. In all conditions the correct scene was chosen among four possible scenes and was dependent on the frame and face that preceded the choice point. One day after training, participants were tested on the retrieval of learned sequences during fMRI scanning. Results showed that the middle and posterior hippocampus (HC) was active at times when participants acquired information that increased predictability of the correct response in the overlapping sequences. Activation of dorsolateral PFC occurred at time points when the participant was able to ascertain which set of sequences the correct response belonged to. The ventrolateral PFC was active when inhibition was required, either of irrelevant stimuli or incorrect responses. These results indicate that areas of lateral PFC work in concert with the HC to disambiguate between overlapping sequences and that sequence predictability is key to when specific brain regions become active.

Figure 1.

Participants learned sequences of contextual cues and associated face-scene combinations. The same faces and scenes were presented with multiple frames and correct responses were dependent on the frame initially shown.

Figure 2.

Low overlap condition. Each frame and face was associated with two scenes, and the correct response was dependent on the frame initially presented. This condition included four sets of two frames, two faces, and two scenes. With each successive sequence element, participants were better able to predict the correct response in this condition.

Figure 3.

One of four sets of stimuli from the high overlap condition. Each frame and face was associated with four scenes, and the correct response was dependent on the frame initially shown. There were 16 overlapping sequences in the high overlap condition. This condition had the highest degree of overlap between sequence elements and the lowest level of predictability.

Figure 4.

Beta weights from each condition at both time points of interest (Cue and Association). The conditions are presented in order of relational load within ROI and timepoint: high overlap (red), low overlap (blue), and control (green).

Figure 5.

A graph showing the average beta weight values for the dorsolateral and ventrolateral PFC during the cue and association periods. Although the ROI used for the small volume correction analysis was comprised of the whole lateral PFC, we discussed the results from this analysis separately for dorsolateral and ventrolateral PFC and therefore show their individual beta weight values.

Figure 6.

(Top row) The posterior HC showed increased activation at time points with increased predictability. In the high overlap condition, at the association time point, the participant was able to accurately predict how to complete the sequence. (Bottom row) In the lateral PFC, the high overlap condition showed increased activation at the association time point. This may be due to the increased level of cognitive control required to inhibit other associations irrevelant to the current trial.

Figure 7.

(Top row) During the cue period, the participant was able to decrease the number of potential upcoming sequences in the low overlap condition to two. This time point also showed increased activation in the posterior HC. (Middle and bottom rows) The low overlap condition showed increased activation in the right dorsolateral PFC that coincided with the participant's increased ability to predict the upcoming sequence.

Figure 8.

(Top row) Whole brain analysis revealed additional regions of activation in the high overlap condition compared to the control during the cue period. (Middle and bottom rows) During the association period, whole brain analyses revealed increased activation in the anterior cingulate cortex, the insula, and dorsolateral PFC, all regions that are part of the cognitive control network, in the high overlap condition compared to the control condition. In addition, compared to the low overlap condition, the high overlap condition showed increased activation in parietal regions including the precuneus, the cuneus, and the angular gyrus.

Figure 9.

(Top row) In the cue period of the low overlap condition, regions associated with memory retrieval (HC and angular gyrus) and cognitive control (dlPFC and SMA) showed increased activation compared to the control condition. (Bottom row) In the association period, the patterns of increased activation in the high and low overlap conditions compared to control were more similar than at the cue period. At this time point the low overlap condition showed increased activation in the SMA, the right dlPFC, and the inferior parietal lobules.