fMRI responses to words repeated in a congruous semantic context are abnormal in mild Alzheimer's disease.

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>or=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 (0.51Old 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.

The precise time course of lexical activation: MEG measurements of the effects of frequency, probability, and density in lexical decision.

Visually presented letter strings consistently yield three MEG response components: the M170, associated with letter-string processing (Tarkiainen, Helenius, Hansen, Cornelissen, & Salmelin, 1999); the M250, affected by phonotactic probability, (Pylkkänen, Stringfellow, & Marantz, 2002); and the M350, responsive to lexical frequency (Embick, Hackl, Schaeffer, Kelepir, & Marantz, 2001). Pylkkänen et al. found evidence that the M350 reflects lexical activation prior to competition among phonologically similar words. We investigate the effects of lexical and sublexical frequency and neighborhood density on the M250 and M350 through orthogonal manipulation of phonotactic probability, density, and frequency. The results confirm that probability but not density affects the latency of the M250 and M350; however, an interaction between probability and density on M350 latencies suggests an earlier influence of neighborhoods than previously reported.

Neuromagnetic evidence for the timing of lexical activation: an MEG component sensitive to phonotactic probability but not to neighborhood density.

Evidence from electrophysiological measures such as ERPs (event-related potentials) and MEG (magnetoencephalography) suggest that the first evoked brain response component sensitive to stimulus properties affecting reaction times in word recognition tasks occurs at 300-400 ms. The present study used the stimulus manipulation of Vitevich and Luce (1999) to investigate whether the M350, an MEG response component peaking at 300-400 ms, reflects lexical or postlexical processing. Stimuli were simultaneously varied in phonotactic probability, which facilitates lexical activation, and in phonological neighborhood density, which inhibits the lexical decision process. The present results indicate that the M350 shows facilitation by phonotactic probability rather than inhibition by neighborhood density. Thus the M350 cannot be a postlexical component.