Replay of Learned Neural Firing Sequences during Rest in Human Motor Cortex

Jean-Baptiste Eichenlaub, Beata Jarosiewicz, Jad Saab, Brian Franco, Jessica Kelemen, Eric Halgren, Leigh R Hochberg, Sydney S Cash, Jean-Baptiste Eichenlaub, Beata Jarosiewicz, Jad Saab, Brian Franco, Jessica Kelemen, Eric Halgren, Leigh R Hochberg, Sydney S Cash

Abstract

The offline "replay" of neural firing patterns underlying waking experience, previously observed in non-human animals, is thought to be a mechanism for memory consolidation. Here, we test for replay in the human brain by recording spiking activity from the motor cortex of two participants who had intracortical microelectrode arrays placed chronically as part of a brain-computer interface pilot clinical trial. Participants took a nap before and after playing a neurally controlled sequence-copying game that consists of many repetitions of one "repeated" sequence sparsely interleaved with varying "control" sequences. Both participants performed repeated sequences more accurately than control sequences, consistent with learning. We compare the firing rate patterns that caused the cursor movements when performing each sequence to firing rate patterns throughout both rest periods. Correlations with repeated sequences increase more from pre- to post-task rest than do correlations with control sequences, providing direct evidence of learning-related replay in the human brain.

Keywords: brain-computer interface; consolidation; human; learning; memory; microelectrode array; motor cortex; reactivation; replay; sleep.

Conflict of interest statement

Declaration of Interests B.J. and B.F. are currently employees of NeuroPace, Inc., and hold stock options in the company. The MGH Translational Research Center has a clinical research support agreement with Neuralink, Paradromics, and Synchron, for which L.R.H. and S.S.C. provide consultative input.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Research Session Setup
Figure 1.. Research Session Setup
(A) Task and timeline. In each session, a decoder was initialized and calibrated using an open-loop and then closed-loop center-out task (see Method Details; calibration inset modified from Jarosiewicz et al., 2015). The participant was then invited to relax with his eyes closed, and nap if desired, during a pre-task rest period (Rest1). Following Rest1, the participant performed the 4-target sequence game, consisting of 66 presentations of the repeated sequence (in this example, red-teal-yellow-blue), interspersed with 22 control sequences. Following the game, the participant was invited to relax with his eyes closed again (Rest2). (B) Participant T9 at his home during a research session. (C) Performance in the game, divided into control and repeated sequences. Each line represents one session from one participant (orange = T9 sessions; cornflower blue = T10 sessions). The success rate (% of sequences correctly completed) was significantly higher for the repeated than the control sequences (Wilcoxon signed-rank test, n = 10, p = 0.0039), suggesting preferential learning of the repeated sequences.
Figure 2.. Replay of Firing Rate Patterns…
Figure 2.. Replay of Firing Rate Patterns in Motor Cortex
(A) Examples of distributions of RIs. One value in each distribution is the RI for one trial (the % change in mean peak CC values from Rest1 to Rest2 when using that trial as the template). The red distributions were obtained using the repeated sequence trials as templates, and the blue distributions were obtained using the control trials. Neural signal nonstationarities can cause spurious drifts in CC values; thus, replay was measured as the difference between the repeated and the control trials’ RIs. In both example sessions (one from each participant), the repeated sequence trials (mean ± SEM in red) showed significantly higher (i.e., more positive) RIs than the control sequence trials (in blue; two-sample one-tailed t test). (B) Difference in mean RI (repeated – control) for each session at all time dilation factors (using a CC threshold at the 95th centile). Sessions with T9 are shown in orange and those with T10 in cornflower blue. The mean across sessions is shown with a thick black line. Asterisks denote time dilation factors at which the repeated-trial mean RIs were significantly higher than the control-trial mean RIs across sessions (paired one-tailed t test, n = 10; *p < 0.01). (C and D) The t scores (C) and corresponding p values (D) resulting from testing, for each time dilation factor and centile threshold, whether the repeated-trial mean RIs were higher than the control-trial mean RIs across sessions (paired one-tailed t test, n = 10). Note that the middle columns of (C) and (D) correspond to the data shown in (B).
Figure 3.. Replay Results across Sessions, with…
Figure 3.. Replay Results across Sessions, with Rest Periods Subdivided into Putative NREM1 and Putative Waking States
(A–C) Analagous to Figures 2B–2D, showing results for putative NREM1. (D–F) Analagous to Figures 2B–2D, showing results for putative waking. *p

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