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

doi:10.1097/JGP.0b013e318162a0a9

The American Journal of Geriatric Psychiatry

Volume 16, Issue 4, April 2008, Pages 283-292

https://doi.org/10.1097/JGP.0b013e318162a0a9 Get rights and content

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.

Section snippets

Subjects

Forty-four elderly individuals participated in the study. All subjects provided informed consent in accordance with the Human Research Committee guidelines of the Massachusetts General Hospital and Brigham and Women's Hospital (Boston, MA). There were 29 healthy OC and 15 mild AD patients (Table 1). Thirty-four of the participants (OC: N = 29; AD: N = 5) were recruited from a longitudinal study examining preclinical predictors of AD. The remaining 10 subjects (AD: N = 10) were recruited from

Demographic and Cognitive Data

The group data for OC and AD are summarized in Table 1. AD patients were older, had less education, lower Mini-Mental State Examination, and poorer postscan memory test performance than the OC.

fMRI Activation Areas in Healthy Older Subjects and Alzheimer Patients

Both OC and AD patient groups demonstrated large brain activation areas in the Repeated versus Fixation (RvF) contrast bilaterally in occipital unimodal and heteromodal visual areas, parietal, anterior cingulate, and insular and prefrontal cortices. Similarly, both OC and AD showed activation in the

DISCUSSION

This study provides evidence that the normal suppression of MTL response to repeated stimuli that are highly familiarized in OC is impaired in AD patients. In addition to increased MTL activation, AD patients showed greater activation than OC in prefrontal and parietal cortical areas of the “novelty detection network” during repeated stimuli. Consistent with previous functional imaging studies, task-induced deactivation was observed in the medial parietal regions in OC but not in AD.

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The authors thank the staff of the Massachusetts General Hospital Gerontology Research Unit and Brigham and Women's Hospital Memory Disorders Unit Clinical Research for assistance with subject recruitment, evaluation, and data management, as well as Mary Foley, Larry White, and the Athinoula A. Martinos Center staff for assistance with MRI data collection. The authors express special gratitude to the subjects who participated in this study.

This work was supported by NIA R01-AG027435, NIA PO1-AG04953, NIA P50-AG00513421, and Academy of Finland.

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Regular Research ArticlesImpaired Medial Temporal Repetition Suppression is Related to Failure of Parietal Deactivation in Alzheimer Disease

Objectives

Design, Setting, Participants and Measurements

Results

Conclusion

Section snippets

Subjects

Demographic and Cognitive Data

fMRI Activation Areas in Healthy Older Subjects and Alzheimer Patients

DISCUSSION

Trends Cogn Sci

Trends Cogn Sci

Neurobiol Aging

Neuropsychologia

Neuroimage

Neuroimage

Am J Geriatr Psychiatry

Neuroimage

Neuron

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Neuroimage

Neural mechanisms for detecting and remembering novel events

Nat Rev Neurosci

Alzheimer's disease: cell-specific pathology isolates the hippocampal formation

Science

Neuropathological staging of Alzheimer-related changes

Acta Neuropathol (Berl)

Alzheimer's disease is a synaptic failure

Science

Functional MR imaging in Alzheimer's disease during memory encoding

Am J Neuroradiol

fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease

J Neurol Neurosurg Psychiatry

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