The Subcortical Default Mode Network and Alzheimer Disease: A systematic review and Activation Likelihood Estimation Meta-Analysis

The default mode network is a central cortical brain network suggested to play a major role in several disorders, and to be particularly vulnerable to the neuropathological hallmarks of Alzheimers disease. Subcortical involvement in the default mode network and its alteration in Alzhimers disease remains largely unknown. We performed a systematic review, meta-analysis, and empirical validation of the subcortical default mode network in healthy adults, combined with a systematic review, meta-analysis, and network analysis of the involvement of subcortical default mode areas in Alzheimers disease. Our results show that, besides the well-known cortical default mode network brain regions, the default mode network consistently includes subcortical regions, namely the thalamus, lobule and vermis IX and right Crus I/II of the cerebellum, and the amygdala. Network analysis also suggests the involvement of the caudate nucleus. In Alzheimers disease, we observed a left-lateralized cluster of decrease in functional connectivity which covered the medial temporal lobe and amygdala and showed overlap with the default mode network in a portion covering parts of the left anterior hippocampus and left amygdala. An increase in functional connectivity was also found in the right anterior insula. These results confirm the consistency of subcortical contributions to the default mode network in healthy adults and highlight the relevance of the subcortical default mode network alteration in Alzheimers disease.