Reactivation of latent working memories with transcranial magnetic stimulation

Abstract

The ability to hold information in working memory is fundamental for cognition. Contrary to the long-standing view that working memory depends on sustained, elevated activity, we present evidence suggesting that humans can hold information in working memory via "activity-silent" synaptic mechanisms. Using multivariate pattern analyses to decode brain activity patterns, we found that the active representation of an item in working memory drops to baseline when attention shifts away. A targeted pulse of transcranial magnetic stimulation produced a brief reemergence of the item in concurrently measured brain activity. This reactivation effect occurred and influenced memory performance only when the item was potentially relevant later in the trial, which suggests that the representation is dynamic and modifiable via cognitive control. The results support a synaptic theory of working memory.

Conflict of interest statement

The authors declare no conflict of interest.

Copyright © 2016, American Association for the Advancement of Science.

Figures

Fig. 1. General procedure

In Phase 1, functional magnetic resonance imaging (fMRI) data were acquired while participants performed a one-item delayed-recognition task for words, faces, or directions of motion (A), and used for multivariate pattern analysis (MVPA). Classifiers trained on the delay-period (B) were used for subsequent analyses. For Experiment 1, these classifiers were used to decode fMRI activity from Phase 2 (Fig. 2). For Experiments 2 and 3, they were used in a whole-brain searchlight, conjunction-analysis to generate subject-specific maps of category-sensitive areas (C); non-overlapping areas were used for transcranial magnetic stimulation (TMS) targeting in Phase 2 (D). In Phase 2, single pulses of TMS (E) were delivered during the post-cue delay periods.

Fig. 2. Experiment 1 fMRI decoding (Train Phase 1, Test Phase 2): Classifier evidence as a function of an item’s status, collapsed across stimulus category

After stimulus presentation (red and blue circles), delay-period classifier evidence for both items was elevated relative to the empirical baseline of evidence for the category that was not presented on that trial (“absent”, gray). Upon presentation of the first cue (red triangle), evidence for the cued category (red) remained elevated, but for the uncued category (blue) dropped to baseline. After the first probe (red square), on half the trials the second cue designated that the same item would be tested by the second probe (A), and evidence for the two categories remained the same relative to baseline. When the second cue designated the previously uncued item (B) evidence for the two categories reversed for the remainder of the trial. (Color-coded markers at the top of each plot indicate p<.01; line width reflects SEM.)

Fig. 3. Experiment 2 EEG decoding (Train and Test on Phase 2 data): Classifier accuracy (area under curve, AUC) as a function of an item’s status at the time of the first cue, collapsed across stimulus category

AUC reflects classifier sensitivity to discriminating between evidence for the AMI or UMI relative to the absent category. (A) Classification timeseries of the AMI and UMI upon stimulus presentation (red and blue circles), the first cue (red triangle), TMS, and first probe (red rectangle), averaged over N=18 sessions, 2,952 trials (decoding ends where the AMI and UMI switched on 50% of the trials). (B) Decoding UMIs as a function of whether TMS targeted that item’s Phase 1-defined region or a different category’s region. (Color-coded markers at the top of each plot indicate p<.05, line width reflects SEM).

Fig. 4

(A) shows the MVPA-defined TMS target for Experiments 3 and 4 (right precuneus). (B) Classification timeseries from Experiment 3 showing TMS reactivation of the UMI following the first cue, when the UMI was still relevant (left panel), but not following the second cue, when the UMI was no longer relevant on the trial (right panel) averaged over 1,152 trials. (C) Experiment 4 recognition memory for AMI match probes, AMI nonmatch probes, and UMI (nonmatch) probes (bars=SEM).