Medial prefrontal theta phase coupling during spatial memory retrieval

Abstract

Memory retrieval is believed to involve a disparate network of areas, including medial prefrontal and medial temporal cortices, but the mechanisms underlying their coordination remain elusive. One suggestion is that oscillatory coherence mediates inter-regional communication, implicating theta phase and theta-gamma phase-amplitude coupling in mnemonic function across species. To examine this hypothesis, we used non-invasive whole-head magnetoencephalography (MEG) as participants retrieved the location of objects encountered within a virtual environment. We demonstrate that, when participants are cued with the image of an object whose location they must subsequently navigate to, there is a significant increase in 4-8 Hz theta power in medial prefrontal cortex (mPFC), and the phase of this oscillation is coupled both with ongoing theta phase in the medial temporal lobe (MTL) and perceptually induced 65-85 Hz gamma amplitude in medial parietal cortex. These results suggest that theta phase coupling between mPFC and MTL and theta-gamma phase-amplitude coupling between mPFC and neocortical regions may play a role in human spatial memory retrieval.

Keywords: MEG; MTL; hippocampus; mPFC; oscillations.

FIGURE 1

Task structure and oscillatory power changes. (a) Structure of the experiment. Participants first navigate freely in a virtual environment and encode object locations during a learning period. After a short break their memory for these object locations is tested. During these retrieval trials a 1.5-s baseline fixation period is followed by a 3-s cue period (highlighted by the red box), where an image of one object is presented on screen. Participants are subsequently required to navigate to the remembered location of that object in the environment and make a response. (b) A 4–8 Hz theta power source reconstruction group-averaged image showing a significant increase in the mPFC (peak at [0; 58; 22], Z-score: 4.39) between baseline and cue periods; and (c) 65–85 Hz high gamma power source reconstruction group-averaged image showing significant increases in the visual cortex (peak at [10; −92; 24], Z-score: 4.00) and precuneus (peak at [−4; −50; 34], Z-score: 3.80) between cue and baseline periods. Both images shown at the statistical threshold of P < 0.001 uncorrected and overlaid on the canonical Montreal Neurological Institute 152 T1 image. (d) Normalized power spectra from a virtual electrode placed at the location in mPFC of the group average peak theta power increase—i.e. [0; 58; 22]—for the cue periods, averaged across n = 17 participants. Note the peak in the 4–8 Hz theta band (delimited with dashed red lines). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

FIGURE 2

mPFC-aMTL theta coupling during retrieval. Group-averaged brain images showing a significant increase in theta phase coupling between the mPFC seed and right aMTL between baseline and cue periods, identified using the (a) phase locking value (PLV, peak at [20; −16; −26], Z-score = 4.52) and (b) phase lag index (PLI, peak at [22; −24; −22], Z-score = 3.48). Both images shown at the statistical threshold of P < 0.001 uncorrected overlaid on the canonical Montreal Neurological Institute 152 T1 image. (c) Circular histogram of theta phase differences between mPFC seed and aMTL voxel exhibiting the group peak PLV increase for a single subject at each time point during a typical baseline and cue period (in this case the PLI values were: baseline PLV = 0.29, cue PLV = 0.36). Note the narrower distribution of phase differences during the cue period. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

FIGURE 3

mPFC theta phase coupling with medial parietal gamma amplitude. (a) Group-averaged brain image showing a significant increase in coupling between mPFC theta phase and medial parietal cortex gamma amplitude between the baseline and cue periods, measured using the PLV (peak at [32; −66; 16], Z-score = 4.77). Image displayed at the statistical threshold of P < 0.001 uncorrected and overlaid on the canonical Montreal Neurological Institute 152 T1 image. (b) Circular histogram of phase differences between theta oscillations in mPFC seed and gamma amplitude in the group peak right medial parietal cortex voxel for a single subject at each time point during a typical baseline and cue period (baseline PLV = 0.34, cue PLV = 0.40). Note the narrower distribution of phase differences during the cue period. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]