Evidence of a Causal Role for mid-Ventrolateral Prefrontal Cortex Based Functional Networks in Retrieving High-Fidelity Memory

Abstract

Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (VLPFC) and angular gyrus in processes associated with retrieving goal-relevant information, which increases the fidelity and richness of long-term memory (LTM). To further investigate the roles of these cortical regions as nodes in functional networks with memory regions of the medial temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to perturb normal neuronal function. The aim was to test the causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal networks that have been associated with high-fidelity memory retrieval. rTMS treatments were administered immediately before blocks in an old/new recognition test, which was based on a mnemonic similarity task requiring discrimination of previously studied pictures of common objects. Capability for mnemonic discrimination was evaluated after each of three conditions: placebo control (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis) and parietal target (rTMS at left AG). The results showed the effect of rTMS perturbation of mid-VLPFC diminished subsequent discrimination-based memory performance, relative to placebo control, and no significant effect of perturbation of AG. These findings show a causal role for functional networks with left mid-VLPFC in high-fidelity retrieval.

Figure 1

Experimental Procedure. (A) A structural scan was collected before a participant (n = 24) completed two test sessions. As illustrated, rTMS treatments were targeted according to fMRI-guided ROI’s (i.e., the left IFG, left AG and right S1) mapped onto each participant’s structural scan using Brainsight™ visualization of their brain in native space. (B) The memory test used a mnemonic discrimination task, which included a study session for all target images presented in that session, and then three test blocks each presenting a random order of targets, similar lures and novel images. On each trial, participants gave an old/new response with a level of confidence. (C) 1 Hz rTMS treatment was applied for the 8m50s immediately preceding test blocks in the PFC (left IFG target), AG (left angular gyrus target) and S1 (right post-central gyrus) conditions. The two test sessions were spaced approximately two weeks apart.

Figure 2

Memory performance by condition. The principal analysis assessed participants’ performance in the memory test in terms of recognizing previously studied targets (A) and correctly rejecting similar lures (B). Gray dots represent scores by response category and condition for each participant, with black bars indicating group means (SEM). Results were compared, as repeated measures, between two response categories (hits|LureCrs) and three rTMS treatment conditions (S1|AG|PFC). ANOVA revealed an interaction of response categories and conditions such that mean hit rates did not differ by condition, while LureCR rates declined in PFC relative to the two other conditions. Planned pairwise tests showed that mean LureCR decreased following rTMS treatment in the PFC condition, relative to S1, the placebo control condition. Mean LureCR following rTMS treatment in the AG condition was not different than either PFC or S1. **Indicates a difference between conditions, p < 0.01. (C) Behavioral results were assessed for each participant’s mnemonic discrimination performance using a lure discrimination index such that LDI = proportion LureCR - proportion NovelFA. ANOVA compared LDI results by condition (S1|AG|PFC). The analysis revealed a main effect of condition, and planned pairwise tests showed that performance in the PFC condition decreased relative to S1 and AG. LDI performance in the AG condition was not different than S1. Blue dots show each participant’s mean LDI scores by condition, black bars indicate group means by condition (SEM), and *Indicates a difference between conditions, p < 0.05.