Excitatory TMS modulates memory representations

Abstract

Brain stimulation technologies have seen increasing application in basic science investigations, specifically toward the goal of improving memory function. However, proposals concerning the neural mechanisms underlying cognitive enhancement often rely on simplified notions of excitation. As a result, most applications examining the effects of transcranial magnetic stimulation (TMS) on functional neuroimaging measures have been limited to univariate analyses of brain activity. We present here analyses using representational similarity analysis (RSA) and encoding-retrieval similarity (ERS) analysis to quantify the effect of TMS on memory representations. To test whether an increase in local excitability in PFC can have measurable influences on upstream representations in earlier temporal memory regions, we compared 1 and 5Hz stimulation to the left dorsolateral PFC (DLPFC). We found that 5Hz rTMS, relative to 1Hz, had multiple effects on neural representations: 1) greater representational similarity during both encoding and retrieval in ventral stream regions, 2) greater ERS in the hippocampus, and, critically, 3) increasing ERS in MTL was correlated with increasing univariate activity in DLPFC, and greater functional connectivity for hits than misses between these regions. These results provide the first evidence of rTMS modulating semantic representations and strengthen the idea that rTMS may affect the reinstatement of previously experienced events in upstream regions.

Keywords: Connectivity; TMS; episodic memory; representational similarity analysis.

Figure 1.. Timeline of imaging protocol.

Figure 2.. Localization of memory-specific rTMS targets, and univariate effects of stimulation.

(A) A functional memory-success localizer collected on Day 1 in individual participants; (B) these subject specific peaks demonstrated a reasonable overlap across participants. (C) Univariate BOLD effects for subsequently Remembered and Forgotten trials during Baseline, 1Hz, and 5Hz conditions reveal a reliable excitation/suppression of the subsequent memory effect after 5Hz/1Hz rTMS. No effect was observed in the contralateral cortex.

Figure 3.

Regions exhibiting significant RSA effects during (A) encoding and (B) retrieval. Model RDMs based on sentential (A) or word pair similarity (B) are shown to the left, while at right are graphs representing mean 2^nd order correlations between model RDMs and brain RDMs.

Figure 4.. Encoding-Retrieval Similarity after 5Hz or 1Hz rTMS.

The schematic on the left describes encoding-retrieval items to be compared (yellow cells) versus set-level matches between unmatched pairs (light purple cells). These set-level matches serve as a reasonable comparison for ERS effects. At right, mean pattern-to-pattern similarity across stimulation conditions for item- and set-level matches.

Figure 5.. Relationships between Left PFC stimulation site and MTL ERS effects.

(A) The increase in univariate activity associated with 5Hz rTMS (see Figure 2) served to boost ERS in left hippocampus after 5Hz rTMS. (B) Functional connectivity estimates based on the cPPI analysis during the encoding period, which demonstrate a selective increase in PFC-MTL connectivity during successfully remembered > forgotten trials, and effect present only in the 5Hz rTMS condition.