The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal–thalamus–hippocampus network

Abstract

The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long‐term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ‐aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face–name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory‐related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory‐related functional connectivity in a medial prefrontal–thalamus–hippocampus network.

Apolipoprotein E ε4 Specifically Modulates the Hippocampus Functional Connectivity Network in Patients With Amnestic Mild Cognitive Impairment

“…The connection between the MPFC and HIP has been implicated in memory transformation (Sekeres et al, 2018 ). Memory-related increased excitatory neurotransmitter levels in MPFC have also been associated with better memory and stronger memory-related functional connectivity in the HIP-MPFC network (Thielen et al, 2018 ). Previous fMRI studies have already showed decreased activity in HIP and MPFC, using amplitude of low-frequency fluctuation in aMCI.…”

Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction

“…The homeostasis between GABA and glutamate is regulated by glia cells which metabolize these amino acids after neurotransmission into glutamine that, in turn, is transported to the neurons where it is synthesized back to glutamate and GABA (Bak, Schousboe, & Waagepetersen, 2006;Behar & Rothman, 2001;Patel et al, 2005;Sickmann, Waagepetersen, Schousboe, Benie, & Bouman, 2012). GABA and glutamate are the main inhibitory and excitatory neurotransmitters in the brain, respectively, and are essential for the formation of episodic memories (Day, Langston, & Morris, 2003;Miranda, 2007;Solomonia & McCabe, 2015;Thielen et al, 2018). Therefore, investigating the quantity of GABA, glutamate and glutamine in relevant brain regions may reveal important new insights into the pathogenesis of T2D related episodic memory impairments.…”

Neural correlates of resilience to the effects of hippocampal atrophy on memory

“…The goal of this study was to identify functional brain mechanisms supporting the hypothesis of cognitive reserve in older adults without dementia. The study focused on processes that protect against the detrimental effect of hippocampal atrophy because the hippocampus is critical for associative memory, and altered by aging and AD ( Atienza et al, 2011 , Chua et al, 2007 , Sperling et al, 2003 , Thielen et al, 2018 ). Our study indicates that there is a moderation effect, where a smaller hippocampal volume is associated with weaker associative memory in participants with lower activation, but not in those with greater activation.…”