Authors: Legaz A, Prado P, Moguilner S, Báez S, Santamaría-García N, Birba A, Barttfeld P, García AM, Fittipaldi S, Ibanez A.

Abstract: Although social functioning relies on working memory, whether a social-specific mechanism exists remains unclear. This undermines the characterization of neurodegenerative conditions with both working memory and social deficits. We assessed working memory domain-specificity across behavioral, electrophysiological, and neuroimaging dimensions in 245 participants. A novel working memory task involving social and non-social stimuli with three load levels was assessed across controls and different neurodegenerative conditions with recognized impairments in: working memory and social cognition (behavioral-variant frontotemporal dementia); general cognition (Alzheimer’s disease); and unspecific patterns (Parkinson’s disease). We also examined resting-state theta oscillations and functional connectivity correlates of working memory domain-specificity. Results in controls and all groups together evidenced increased working memory demands for social stimuli associated with frontocinguloparietal theta oscillations and salience network connectivity. Canonical frontal theta oscillations and executive-default mode network anticorrelation indexed non-social stimuli. Behavioral-variant frontotemporal dementia presented generalized working memory deficits related to posterior theta oscillations, with social stimuli linked to salience network connectivity. In Alzheimer’s disease, generalized working memory impairments were related to temporoparietal theta oscillations, with non-social stimuli linked to the executive network. Parkinson’s disease showed spared working memory performance and canonical brain correlates. Findings support a social-specific working memory and related disease-selective pathophysiological mechanisms..