Alterations in default mode network functional connectivity in semantic dementia

Progressive deterioration of semantic memory is a defining characteristic of the semantic variant of primary progressive aphasia or semantic dementia (SD). Semantic deficits in SD are classically attributed to temporal lobe atrophy, in particular in the anterior temporal lobe. Recent neuroimaging studies have associated SD with disruptions of intrinsic connectivity networks during task and at rest, predominantly implicating regions of the semantic and language networks. Yet, anterior temporal lobe atrophy disrupts connectivity within the Default Mode Network (DMN), particularly in the anterior portions associated with semantic memory. Few neuroimaging studies have focussed on DMN connectivity in SD and links to semantic memory impairments. Using whole-brain seed-based connectivity analyses during resting state fMRI, we examined DMN functional connectivity in eight bilateral seeds and the association with semantic impairments in 16 SD compared to 20 age-matched healthy participants. Patients exhibited within DMN hypoconnectivity between the anterior hippocampus and medial orbito-frontal cortex, on the right, and between the posterior cingulate cortex and middle temporal gyrus, on the left. Furthermore, functional connectivity of the left posterior cingulate cortex with the middle temporal gyrus correlated positively with left lateral temporal atrophy in SD patients. Correlations with semantic performances showed that connectivity of the right anterior hippocampus and left middle/superior frontal gyri correlated positively with animal fluency in controls, but not in patients. In SD, connectivity between the left posterior cingulate cortex and left cerebellum area 9 correlated positively with semantic knowledge. These findings provide evidence that semantic SD impairments are subserved by altered DMN functional connectivity, linked to atrophy in the anterior temporal lobes and anterior hippocampi.