Functional brain network correlates of theory of mind and social cognition in early Alzheimer’s disease

Abstract

AbstractBackgroundPatients in the early stages of Alzheimer’s disease (AD) may display impairment of social cognition (SC) such as the ability to attribute intentions, beliefs or emotions to others (Theory of Mind, ToM). In healthy subjects, SC relies on multi‐network interactions that modulate brain social processing. Therefore, specific pathological changes in multiple large‐scale networks could explain the heterogeneous results of SC performance in AD found across the literature. To date, there is no resting‐state connectivity study investigating the network underpinnings of SC in AD patients.MethodsResting‐state functional MRI scans were acquired from early‐AD patients (n=46) and preprocessed using the Statistical Parametric Mapping (SPM) 12 software. Independent component analysis (ICA) was performed at a group level to isolate and reconstruct four intrinsic connectivity brain large‐scale networks, namely fronto‐parietal, salience, and anterior and posterior default mode networks (DMN). Multiple regression analyses were performed on three SC tasks of emotion recognition (ER) (Ekman 60 face task) and ToM (Reading‐the‐Mind‐in‐the‐Eyes‐Test, RMET and the Story‐based Empathy Task, SET) with the ICA extracted large‐scale network maps, controlling for age, cognitive reserve, brain reserve and disease severity.ResultsSC associations with functional connectivity maps showed positive correlations (increased intrinsic connectivity) between ER and the fronto‐parietal network in the right insular region (p <0.034) and ToM (SET) with the posterior DMN in the right precuneus (p <0.030). Conversely, negative associations (decreased intrinsic connectivity) were found between ToM‐RMET (p < 0.011), ToM‐SET (p< 0.049) and ER (p < 0.034) and the salience network in the left temporo‐parietal junction, precuneus, uncus, inferior temporal gyrus and right postcentral gyrus. Lastly, a negative association was found between ToM‐RMET and the anterior DMN (p < 0.013) in the right medial prefrontal cortex.ConclusionsThis study sheds light on how multiple network dynamics exhibit particular connectivity dissociation patterns of social processing in AD. Specific neural reorganisation via up‐regulation of the posterior DMN and fronto‐parietal network concomitant with a down‐regulation of the salience and anterior DMN could explain the characteristic pattern of decline of SC in AD. Notably, our results display consistency with regions involved in SC and ToM.