BRAIN-WIDE AMPA RECEPTOR–MEDIATED SYNAPTIC PLASTICITY FOLLOWING HEARING LOSS AND RESTORATION IN HUMANS

Auditory cortical plasticity is thought to underlie functional recovery after cochlear implantation (CI); however, its molecular basis in the human brain remains poorly understood. AMPA receptors are fundamental molecules of synaptic plasticity, and the amount of AMPA receptors at synapses determines the strength of functional connectivity between neurons. In this study, we evaluated synaptic plasticity by visualizing AMPA receptors during the recovery after CI, using the novel PET tracer [¹¹C]K-2, which enables the visualization and quantification of AMPA receptors in the living human brain. Thirty adults with acquired bilateral severe-to-profound hearing loss underwent [¹¹C]K-2 PET imaging before and six months after cochlear implantation. Voxel-wise analyses were performed using SPM12. AMPA receptor binding was quantified as standardized uptake value ratios (SUVR) with white-matter reference (absolute density) and whole-brain reference normalization (relative density). Compared with healthy controls, preoperative CI candidates showed globally elevated absolute AMPA receptor density. Longitudinal analysis revealed a global postoperative decrease, although AMPA receptor density remained elevated relative to healthy controls. Relative analysis demonstrated postoperative increases in AMPA receptor density within the left temporal regions, including Wernicke’s area, as well as in occipital regions corresponding to the lingual gyrus and adjacent V1/V2 areas, accompanied by relative decreases in bilateral parietal regions and the right fusiform area. This study provides the first in vivo molecular evidence of AMPA receptor–mediated synaptic plasticity in the human brain after hearing loss and restoration, revealing large-scale absolute changes alongside region-specific postoperative increases within the language-dominant auditory cortex.