Anosognosia and default mode subnetwork dysfunction in Alzheimer's disease

Abstract

Research on the neural correlates of anosognosia in Alzheimer's disease varied according to methods and objectives: they compared different measures, used diverse neuroimaging modalities, explored connectivity between brain networks, addressed the role of specific brain regions or tried to give support to theoretical models of unawareness. We used resting-state fMRI connectivity with two different seed regions and two measures of anosognosia in different patient samples to investigate consistent modifications of default mode subnetworks and we aligned the results with the Cognitive Awareness Model. In a first study, patients and their relatives were presented with the Memory Awareness Rating Scale. Anosognosia was measured as a patient-relative discrepancy score and connectivity was investigated with a parahippocampal seed. In a second study, anosognosia was measured in patients with brain amyloid (taken as a disease biomarker) by comparing self-reported rating with memory performance, and connectivity was examined with a hippocampal seed. In both studies, anosognosia was consistently related to disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes. Importantly, scores were also related to disconnection between the medial temporal and both the core subsystem (participating to self-reflection) and the dorsomedial subsystem of the default mode network (the middle temporal gyrus that might subserve a personal database in the second study). We suggest that disparity in connectivity within and between subsystems of the default mode network may reflect impaired functioning of pathways in cognitive models of awareness.

Keywords: Alzheimer's disease; anosognosia; connectivity; default mode network; memory; self.

Figure 1

Voxel‐wise regression analysis between memory awareness rating scale (MARS) anosognosia scores and parahippocampal cortex (PHC) seed‐based connectivity maps in Alzheimer's patients. The cluster obtained in the CONN analysis was used as a mask to extract values used in the graph (mean value over the cluster)

Figure 2

Voxel‐wise regression analysis between Memory Awareness Rating Scale—Adapted (MARSA) anosognosia scores and hippocampal seed‐based connectivity maps in Alzheimer's patients. The cluster obtained in the CONN analysis was used as a mask to extract values used in the graph (mean value over the cluster)

Figure 3

A simplified representation of the cognitive awareness model. Brain regions in the DMN showing disconnection with our medial temporal seed regions are superimposed on the model. dmPF, dorsomedial prefrontal; IPL, inferior parietal cortex; MT, medial temporal; MTG, middle temporal gyrus; PCC, posterior cingulate cortex; RS, retrosplenial cortex; vmPF, ventromedial prefrontal cortex