Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory

Abstract

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

Keywords: Dorsolateral prefrontal cortex; Granger causality; Hippocampus; Phase coherence; Sequential working memory; Stereoelectroencephalography (SEEG); Theta oscillations.

Fig. 1

Line ordering task. A In the line ordering task, participants were asked to arrange four lines clockwise and memorize them over a short delay. B Lines with different orientations and locations. C Participants reproduced the orientation of the target line by rotating and pressing a response dial.

Fig. 2

Task performance. A The probabilistic model of response error. B Individual data, group means, and SEMs of the thinking time and response error in ordered (ORD) and random trials (RAN). *P <0.025 (one-tailed paired t-test, 20 participants). C Means and SEMs of the probability of misbinding and guessing errors. *P <0.025 (one-tailed paired t-test, 20 participants).

Fig. 3

TFRs in the encoding and delay stages. A Grand-average TFRs for ordered (ORD) and random trials (RAN) and their differences (RAN>ORD) in the hippocampus and dorsolateral prefrontal cortex (DLPFC). Dashed lines indicate the stage onsets. Color bars indicate baseline-corrected normalized power values and power differences. Black outlines indicate significant clusters (permutation test, 56 hippocampal sites, 43 DLPFC sites, P <0.05 corrected). B Regions and sites of interest in the MNI coordinate system. R, right. C Means and SEMs of hippocampal theta powers for good and bad trials in the encoding stage. *P <0.05 (linear mixed model, 56 hippocampal sites). D Means and SEMs of theta power differences (RAN>ORD) for good and bad trials in the encoding stage. *P <0.05 (linear mixed model, 56 hippocampal sites).

Fig. 4

Inter-regional theta phase coherences in the encoding and delay stages. A Grand-average theta phase coherences between the dorsolateral prefrontal cortex (DLPFC) and hippocampus (HP) for ordered (ORD) and random trials (RAN) and their differences (RAN>ORD). Dashed lines indicate the stage onsets. Color bars indicate baseline-corrected normalized coherence values and coherence differences. Black outlines indicate significant clusters (permutation test, 139 DLPFC-HP site pairs, P <0.05 corrected). B Means and SEMs of theta phase coherences for good and bad trials in the encoding and delay stages. *P <0.025 (linear mixed model, 139 DLPFC-HP site pairs). C Means and SEMs of theta phase coherence differences (RAN>ORD) for good and bad trials in the encoding and delay stages. *P <0.025 (linear mixed model, 139 DLPFC-HP site pairs).

Fig. 5

Theta-band Granger causality in the encoding and delay stages. A Theta-band Granger causality from the dorsolateral prefrontal cortex to the hippocampus (DLPFC → HP) and from the hippocampus to the DLPFC (HP → DLPFC) for ordered (ORD) and random trials (RAN). Asterisks, P <0.05 corrected (linear mixed model, 139 DLPFC-HP site pairs). B The theta-band DLPFC → HP influence for RAN versus ORD trials. Asterisks, P <0.05 corrected (linear mixed model, 139 DLPFC-HP site pairs).