Network interactions explain effective encoding in the context of medial temporal damage in MCI.

Selective dysfunction in the medial temporal lobe (MTL) in amnestic mild cognitive impairment (MCI) results in a relatively circumscribed impairment in episodic memory. Previously, we found that activation extent in MTL during encoding correlated with subsequent recognition (hit rate) in controls but not in MCI patients (Mandzia et al. [2009]: Neurobiol Aging 30:717-730). Here, we examined whether functional connectivity amongst MTL and cortical regions might better explain differences in subsequent recognition success. Participants underwent fMRI scanning during picture encoding, and multivariate analysis was used to characterize the relationship between network activations and recognition. Both patients and controls activated a canonical MTL encoding network. However, this network correlated with hit rate only for controls. In MCI patients, recognition variability was best explained by the engagement of an additional network including BA 20. We propose that this pattern represents functional reorganization caused by reduced efficiency in the MTL network. Our findings suggest that understanding brain-behavior relationships in neurological disorders requires examination of large-scale networks, even when dysfunction is relatively focal as in MCI.