Several functional neuroimaging studies have compared words and pseudowords to test different cognitive models of reading. There are difficulties with this approach, however, because cognitive models do not make clear-cut predictions at the neural level. Therefore, results can only be interpreted on the basis of prior knowledge of cognitive anatomy. Furthermore, studies comparing words and pseudowords have produced inconsistent results. The inconsistencies could reflect false-positive results due to the low statistical thresholds applied or confounds from nonlexical aspects of the stimuli. Alternatively, they may reflect true effects that are inconsistent across subjects; dependent on experimental parameters such as stimulus rate or duration; or not replicated across studies because of insufficient statistical power.

In this fMRI study, we investigate consistent and inconsistent differences between word and pseudoword reading in 20 subjects, and distinguish between effects associated with increases and decreases in activity relative to fixation. In addition, the interaction of word type with stimulus duration is explored. We find that words and pseudowords activate the same set of regions relative to fixation, and within this system, there is greater activation for pseudowords than words in the left frontal operculum, left posterior inferior temporal gyrus, and the right cerebellum. The only effects of words relative to pseudowords consistent over subjects are due to decreases in activity for pseudowords relative to fixation; and there are no significant interactions between word type and stimulus duration. Finally, we observe inconsistent but highly significant effects of word type at the individual subject level.

These results (i) illustrate that pseudowords place increased demands on areas that have previously been linked to lexical retrieval, and (ii) highlight the importance of including one or more baselines to qualify word type effects. Furthermore, (iii) they suggest that inconsistencies observed in the previous literature may result from effects arising from a small number of subjects only.

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