Abstract
The distinction between letter strings that form words and those that look and sound plausible but are not meaningful is a basic one. Decades of functional neuroimaging experiments have used this distinction to isolate the neural basis of lexical (word-level) semantics, associated with areas such as the middle temporal, angular, and posterior cingulate gyri that overlap the default-mode network. In two functional magnetic resonance imaging (fMRI) experiments, a different set of findings emerged when word stimuli were used that were less familiar (measured by word frequency) than those typically used. Instead of activating default-mode network areas often associated with semantic processing, words activated task-positive areas such as the inferior prefrontal cortex and supplementary motor area, along with multi-functional ventral occipito-temporal cortices related to reading, while nonwords activated default-mode areas previously associated with semantics. Effective connectivity analyses of fMRI data on less familiar words showed activation driven by task-positive and multi-functional reading-related areas, while highly familiar words showed bottom-up activation flow from occipito-temporal cortex. These findings suggest functional neuroimaging correlates of semantic processing are less stable than previously assumed, with factors such as word frequency influencing the balance between task-positive, reading-related, and default-mode networks. More generally, this suggests results of contrasts typically interpreted in terms of semantic content may be more influenced by factors related to task difficulty than is widely appreciated.