OBJECTIVE: Semantic memory impairment has been documented in individuals with amnestic Mild cognitive impairment (aMCI), who are at risk of developing Alzheimer’s disease (AD), yet little is known about the neural basis of this breakdown. The aim of this study was to investigate the brain mechanisms associated with semantic performance in aMCI patients. METHOD: A group of aMCI patients and a group of healthy controls carried out a semantic categorization task while their brain activity was recorded using magnetoencephalography (MEG). During the task, participants were shown famous faces and had to determine whether each famous person matched a given occupation. The main hypotheses were that (a) semantic processing should be compromised for aMCI patients, and (b) these deficits should be associated with cortical dysfunctions within specific areas of the semantic network. RESULTS: Behavioral results showed that aMCI participants were significantly slower and less accurate than controls at the semantic task. Additionally, relative to controls, a significant pattern of hyperactivation was found in the aMCI group within specific regions of the extended semantic network, including the right anterior temporal lobe (ATL) and fusiform gyrus. CONCLUSIONS: Abnormal functional activation within key areas of the semantic network suggests that it is compromised early in the disease process. Moreover, this pattern of right ATL and fusiform gyrus hyperactivation was positively associated with gray matter integrity in specific areas, but was not associated with any pattern of atrophy, suggesting that this pattern of hyperactivation may precede structural alteration of the semantic network in aMCI. (PsycINFO Database Record