TY - JOUR
T1 - FMRI responses to words repeated in a congruous semantic context are abnormal in mild Alzheimer's disease
AU - Olichney, John M.
AU - Taylor, Jason R.
AU - Chan, Shiaohui
AU - Yang, Jin Chen
AU - Stringfellow, Andrew
AU - Hillert, Dieter G.
AU - Simmons, Amanda L.
AU - Salmon, David P.
AU - Iragui-Madoz, Vicente
AU - Kutas, Marta
N1 - Funding Information:
Funding: Supported by NIH grants # R01-AG18442 , R01-AG08313 , P30-AG10129 and P50-AG05131 and the California Department of Health's Alzheimer's Disease Program.
PY - 2010/7
Y1 - 2010/7
N2 - Background: We adapted an event-related brain potential word repetition paradigm, sensitive to early Alzheimer's disease (AD), for functional MRI (fMRI). We hypothesized that AD would be associated with reduced differential response to New/Old congruous words. Methods: Fifteen mild AD patients (mean age = 72.9) and 15 normal elderly underwent 1.5T fMRI during a semantic category decision task. Results: We found robust between-groups differences in BOLD response to congruous words. In controls, the New > Old contrast demonstrated larger responses in much of the left-hemisphere (including putative P600 generators: parahippocampal, cingulate, fusiform, perirhinal, middle temporal (MTG) and inferior frontal gyri (IFG)); the Old > New contrast showed modest activation, mainly in right parietal and prefrontal cortex. By contrast, there were relatively few regions of significant New > Old responses in AD patients, mainly in the right-hemisphere, and their Old > New contrast did not demonstrate a right-hemisphere predominance. Across subjects, the spatial extent of New > Old responses in left medial temporal lobe (MTL) correlated with subsequent recall and recognition (r's ≥ 0.60). In controls, the magnitude of New-Old response in left MTL, fusiform, IFG, MTG, superior temporal and cingulate gyrus correlated with subsequent cued recall and/or recognition (0.51 ≤ r's ≤ 0.78). Conclusions: A distributed network of mostly left-hemisphere structures, which are putative P600 generators, appears important for successful verbal encoding (with New > Old responses to congruous words in normal elderly). This network appears dysfunctional in mild AD patients, as reflected in decreased word repetition effects particularly in left association cortex, paralimbic and MTL structures.
AB - Background: We adapted an event-related brain potential word repetition paradigm, sensitive to early Alzheimer's disease (AD), for functional MRI (fMRI). We hypothesized that AD would be associated with reduced differential response to New/Old congruous words. Methods: Fifteen mild AD patients (mean age = 72.9) and 15 normal elderly underwent 1.5T fMRI during a semantic category decision task. Results: We found robust between-groups differences in BOLD response to congruous words. In controls, the New > Old contrast demonstrated larger responses in much of the left-hemisphere (including putative P600 generators: parahippocampal, cingulate, fusiform, perirhinal, middle temporal (MTG) and inferior frontal gyri (IFG)); the Old > New contrast showed modest activation, mainly in right parietal and prefrontal cortex. By contrast, there were relatively few regions of significant New > Old responses in AD patients, mainly in the right-hemisphere, and their Old > New contrast did not demonstrate a right-hemisphere predominance. Across subjects, the spatial extent of New > Old responses in left medial temporal lobe (MTL) correlated with subsequent recall and recognition (r's ≥ 0.60). In controls, the magnitude of New-Old response in left MTL, fusiform, IFG, MTG, superior temporal and cingulate gyrus correlated with subsequent cued recall and/or recognition (0.51 ≤ r's ≤ 0.78). Conclusions: A distributed network of mostly left-hemisphere structures, which are putative P600 generators, appears important for successful verbal encoding (with New > Old responses to congruous words in normal elderly). This network appears dysfunctional in mild AD patients, as reflected in decreased word repetition effects particularly in left association cortex, paralimbic and MTL structures.
KW - Cingulate
KW - Language
KW - Medial temporal lobe
KW - Memory
KW - Semantic
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U2 - 10.1016/j.neuropsychologia.2010.04.021
DO - 10.1016/j.neuropsychologia.2010.04.021
M3 - Article
C2 - 20433856
AN - SCOPUS:77954459686
SN - 0028-3932
VL - 48
SP - 2476
EP - 2487
JO - Neuropsychologia
JF - Neuropsychologia
IS - 9
ER -