Defaulting on the default network

The past decade of cognitive neuroscience and neuroimaging research has yielded several critical insights into the organization of the human brain, in particular, the existence of multiple large-scale functional networks. Several of these networks map easily onto conventional notions regarding brain–behavior relationships, such as intrinsic networks subserving motor, sensory, and language function. Perhaps the least intuitive network and arguably the most salient for the study of dementia is a set of brain regions, including the posterior cingulate, precuneus, lateral parietal, lateral temporal, and medial prefrontal cortices, collectively known as the default mode network (DMN). This nomenclature arose from the initial observation in PET studies that these regions show the greatest activity during the resting or “default” state, and demonstrate a marked decrease in activity during cognitive tasks involving externally directed attention.^1,2 Multiple fMRI studies, during both cognitive tasks and resting state, have confirmed strong intercorrelations among the DMN cortical regions, as well as functional connectivity with the hippocampus and related structures within medial temporal lobe. The DMN is known to subserve a number of key memory processes, including episodic encoding and retrieval, autobiographical and metamemory processes, as well as other complex cognitive constructs, including moral decision-making and “theory of mind.”

In this issue of Neurology®, Petrella et al.³ report that DMN connectivity was significantly lower in a group of patients with mild cognitive impairment (MCI) who subsequently progressed to a diagnosis of Alzheimer disease (AD) over a period of 2–3 years, compared to patients with MCI who did not decline. Importantly, the study also demonstrated that DMN connectivity provided additional information in predicting the likelihood of progression among the patients with MCI, above and beyond age, Mini-Mental State Examination score, and gray matter volume at baseline. Interestingly, DMN connectivity did not remain a significant predictor …