Impairment of the Missing Fundamental Phenomenon in Individuals with Alzheimer's Disease: A Neuropsychological and Voxel-Based Morphometric Study

BACKGROUND/AIMS: The missing fundamental phenomenon (MFP) is a universal pitch perception illusion that occurs in animals and humans. In this study, we aimed to determine whether the MFP is impaired in patients with Alzheimer's disease (AD) using an auditory pitch perception experiment. We further examined anatomical correlates of the MFP in patients with AD by measuring gray matter volume (GMV) on magnetic resonance images via voxel-based morphometric analysis. METHODS: We prospectively enrolled 29 patients with AD and 20 healthy older adults. Auditory stimuli included 12 melodies of Japanese nursery songs that were expected to be familiar to participants. We constructed the melodies using pure and missing fundamental tones (MFTs). RESULTS: Patients with AD exhibited significantly poorer performance on the MFT task than healthy controls. MFT scores were positively correlated with GMV in the bilateral insula and temporal poles, left inferior frontal gyrus, right entorhinal cortex, and right cerebellum. CONCLUSIONS: These results suggest that impairments in the MFP represent a manifestation of the degeneration of auditory-related brain regions in AD. Further studies are required to more fully elucidate the neural mechanisms underlying auditory impairments in patients with AD and related dementia disorders.