Genetic and brain atrophy markers associated with different psychological phenotypes within ADNI

Abstract

room. Patients with Alzheimer’s disease (AD) typically have difficulty with tasks requiring ASA and anatomical regions implicated in ASA in the healthy brain are vulnerable in AD, suggesting that ASAmay provide a window on AD pathophysiology. Methods: Here we studied the brain mechanism of the ’cocktail party effect’ using 3T fMRI in a cohort of patients fulfilling consensus criteria for typical AD in relation to age-matched healthy subjects.We designed a ’sparse’ image acquisition, passive listening paradigm to minimise extraneous cognitive or task-related attentional demands, control low-level auditory perceptual features and optimise signal detection. We reasoned that the cocktail party effect would be captured by the differential ASA demands during processing of sound conditions where the auditory target was a learned template (one’s own name) versus a comparably acoustically complex but unfamiliar sound object (one’s own name spectrally rotated). Subjects heard four stimulus conditions: i) their own name interleaved with babble, ii) own name superimposed on babble, iii) own name spectrally rotated (rendered unrecognisable) and interleaved with babble, or iv) own name spectrally rotated and superimposed on babble. Results: Compared with healthy older controls, AD patients showed heightened activation in posterior hippocampus during ’cocktail party’ processing. Conclusions: Our findings suggest that ASA is a model of generic cortical information processing that can be used to probe obligatory pathophysological mechanisms of AD, including abnormally heightened or compensatory processes. This work goes beyond the traditional emphasis on higher cognitive and mnestic functions in AD: besides illuminating an important but poorly understood class of perceptual symptoms, such work promises novel insights into neural network dysfunction underpinning AD.