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Impaired Medial Temporal Repetition Suppression is Related to Failure of Parietal Deactivation in Alzheimer Disease

From the Memory Disorders Unit, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (MP, KMD, RAS); Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland (MP); and Department of Psychiatry (MP, KMD, DB, RAS) and Athinoula A. Martinos Center for Biomedical Imaging (RAS), Massachusetts General Hospital, Boston, MA.

Objectives: Neural networks supporting encoding of new information are affected early in the course of Alzheimer disease (AD). Functional magnetic resonance imaging (fMRI) studies in AD have reported decreased medial temporal lobe (MTL) activation when comparing novel versus repeated stimuli. It is, however, unclear whether this finding is related to a failure of normal suppression of MTL activity to repeated stimuli in AD.

Design, Setting, Participants and Measurements: Twenty-nine healthy older subjects comprising a comparison group (OC) and 15 mild AD patients underwent fMRI during an associative memory paradigm in an academic medical center. The task consisted of blocks of Novel and Repeated face-name pairs and visual Fixation. To reveal neural correlates of processing repeatedly presented stimuli, Repeated blocks were contrasted to Fixation.

Results: AD patients demonstrated greater activation during Repeated stimuli in the MTL and in prefrontal and superior parietal cortices, compared with OC. In contrast, OC showed greater parietal task-induced deactivation than AD. Increased MTL activity during Repeated was correlated with more impaired parietal deactivation and poorer performance of the postscan recognition memory test of encoding the face-name pairs.

Conclusion: Reduction of MTL activity to repeated stimuli, which become highly familiarized to healthy OC, was impaired in AD. This abnormal increased MTL activation was related to disrupted parietal deactivation and to poor recognition memory performance. These preliminary results suggest that the typical episodic memory impairment seen in mild AD may manifest as a failure of normal repetition suppression and loss of "beneficial" deactivation in the MTL-parietal memory networks.

Key Words: Alzheimer disease • fMRI • medial temporal lobe • memory • parietal cortex • repetition suppression

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