Amnestic mild cognitive impairment (aMCI) is the transitional, heterogeneous continuum from normal elderly to Alzheimer's disease (AD). Previous studies have shown that brain functional activity in the default mode network (DMN) is impaired in aMCI patients with saliently cognitive and memory decline. However, the effective connectivity among the spatially isolated, but functionally related areas within the DMN in aMCI patients remains largely unknown. The present study examined dysfunctional connectivity of the DMN by combining an independent component analysis (ICA) approach with multivariate Granger causality analysis (mGCA) in 18 aMCI patients and 18 age-matched cognitively normal elderly. Results from mGCA showed decreased effective connectivity occurred among the middle temporal gyrus (MTG), hippocampus (HC) and fusiform gyrus (FG), as well as between the precuneus/posterior cingulate cortex (PreCN/PCC) and HC in patients with aMCI. Such an impaired connectivity was also correlated with patients' cognitive performance of the auditory verbal learning. Moreover, enhanced effective connectivity within frontal cortex emerged, which may maintain memory functions after attenuated connections within DMN activity. These findings may elucidate the dysfunctional processes in brain networks of aMCI patients, highlighting the importance of connectivity changes in the pathophysiology of aMCI. (JINS, 2013, 19, 400-409)