An impaired excitatory-inhibitory balance in the right inferior temporal gyrus of patients with Alzheimer's disease correlated with executive function

Abstract

Preliminary research indicates that an imbalance between excitation and inhibition may be an early pathological feature of Alzheimer's disease. However, the relevant brain networks, neurotransmitters and genetic mechanisms are still unclear. This study enrolled 27 patients with Alzheimer's disease (AD), 86 patients with mild cognitive impairment MCI, and 85 healthy controls (HC), all aged 65 or older, from the ADNI3 cohort in May 2024. We employed analysis of covariance to compare abnormalities in the excitation-inhibition balance across the three groups. We performed a transcriptomic analysis of abnormal excitation-inhibition imbalance. To elucidate the characteristics of the underlying brain networks, we extracted brain regions exhibiting differences in the balance of excitation and inhibition for seed-based functional connectivity analysis. Compared to the HC group, AD exhibits a significant putative excitatory-inhibitory imbalance in the right inferior temporal gyrus and superior orbital frontal gyrus. The Hurst exponent of the right inferior temporal gyrus was significantly correlated with executive function. Transcriptomic analysis revealed that the abnormal excitation-inhibition imbalance observed in AD patients is significantly associated with GABA and mGluR5 receptors, as well as with genes that are enriched in the GABAergic synapse pathway. Functional connectivity analysis using the right inferior temporal gyrus as a seed point revealed significant abnormalities in the frontoparietal control network in AD patients. Our findings suggest that an imbalance between excitation and inhibition in the inferior temporal gyrus is a potential pathological mechanism underlying AD. This imbalance also leads to functional abnormalities in the frontoparietal control network associated with executive functions.