Regional Excitatory-Inhibitory Balance Relates to Self-Reference Effect on Recollection via the Precuneus/Posterior Cingulate Cortex–Medial Prefrontal Cortex Connectivity

• DOI: 10.1523/jneurosci.2343-24.2025
• Publication Date: 2025-05-20T17:50:19Z
• Authors: Ying He; Hilary Sweatman; Alice R. Thomson; Zeus Garcia Tabuenca; Nicolaas A. Puts; Xiaoqian J. Chai
• Keywords: Posterior cingulate; Neurochemical; Self-reference effect

Self-related representation can enhance perception and memory —a phenomenon known as the self-referential effect (SRE). While SRE has been linked to activation of default mode network (DMN), including precuneus/posterior cingulate cortex (Pcu/PCC) medial prefrontal (mPFC), underlying neurochemical processes DMN activations remain unclear. The balance excitation inhibition (E/I balance) within brain circuits is crucial for cognition may play a role in SRE. We examine whether ratio glutamate/glutamine (Glx) γ-aminobutyric acid (GABA) concentrations, measured by 1 H-Magnetic Resonance Spectroscopy ( H-MRS) proxy measure E/I balance, associated with neural involved encoding. Fifty-four healthy participants aged 7-35 (25 female) underwent MRS levels Glx GABA Pcu/PCC, completed functional Magnetic Imaging (fMRI) scan during an encoding task that semantic judgments. found self-related condition led better subsequent greater Pcu/PCC compared condition. Activations was positively correlated Glx/GABA+ ratio. Task-dependent connectivity analysis revealed between (mPFC) both on recollection accuracy. Furthermore, mediation showed higher through increased Pcu/PCC-mPFC connectivity. Our study provides valuable insights into how activity via large-scale networks. Significance Statement — excitatory/inhibitory key nodes DMN. These findings indicate critical processes, which provide new psychiatric disorders characterized impaired self-awareness.