Understanding the neural basis of recovery from stroke is a major research goal. Many functional neuroimaging studies have identified changes in brain activity in people with aphasia, but it is unclear whether these changes truly support successful performance or merely reflect increased task difficulty. We addressed this problem by examining differences in brain activity associated with correct and incorrect responses on an overt reading task. On the basis of previous proposals that semantic retrieval can assist pronunciation of written words, we hypothesized that recruitment of semantic areas would be greater on successful trials. Participants were 21 patients with left-hemisphere stroke with phonologic retrieval deficits. They read words aloud during an event-related fMRI paradigm. BOLD signals obtained during correct and incorrect trials were contrasted to highlight brain activity specific to successful trials. Successful word reading was associated with higher BOLD signal in the left angular gyrus. In contrast, BOLD signal in bilateral posterior inferior frontal cortex, SMA, and anterior cingulate cortex was greater on incorrect trials. These data show for the first time the brain regions where neural activity is correlated specifically with successful performance in people with aphasia. The angular gyrus is a key node in the semantic network, consistent with the hypothesis that additional recruitment of the semantic system contributes to successful word production when phonologic retrieval is impaired. Higher activity in other brain regions during incorrect trials likely reflects secondary engagement of attention, working memory, and error monitoring processes when phonologic retrieval is unsuccessful.

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 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 pFC and SMA, along with multifunctional ventral occipitotemporal cortices related to reading, whereas 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 multifunctional reading-related areas, whereas highly familiar words showed bottom–up activation flow from occipitotemporal cortex. These findings suggest that 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 that results of contrasts typically interpreted in terms of semantic content may be more influenced by factors related to task difficulty than is widely appreciated.

Impairments in phonological processing have been associated with damage to the region of the left posterior superior temporal gyrus (pSTG), but the extent to which this area supports phonological processing, independent of semantic processing, is less clear. We used repetition priming and neural repetition suppression during functional magnetic resonance imaging (fMRI) in an auditory pseudoword repetition task as a semantics-free model of lexical (whole-word) phonological access. Across six repetitions, we observed repetition priming in terms of decreased reaction time and repetition suppression in terms of reduced neural activity. An additional analysis aimed at sublexical phonology did not show significant effects in the areas where repetition suppression was observed. To test if these areas were relevant to real word production, we performed a conjunction analysis with data from a separate fMRI experiment which manipulated word frequency (a putative index of lexical phonological access) in picture naming. The left pSTG demonstrated significant effects independently in both experiments, suggesting that this area participates specifically in accessing lexical phonology.

Cognitive models of word production correlate the word frequency effect (i.e., the fact that words which appear with less frequency take longer to produce) with an increased processing cost to activate the whole-word (lexical) phonological representation. We performed functional magnetic resonance imaging (fMRI) while subjects produced overt naming responses to photographs of animals and manipulable objects that had high name agreement but were of varying frequency, with the purpose of identifying neural structures participating specifically in activating whole-word phonological representations, as opposed to activating lexical semantic representations or articulatory-motor routines. Blood oxygen level-dependent responses were analyzed using a parametric approach based on the frequency with which each word produced appears in the language. Parallel analyses were performed for concept familiarity and word length, which provided indices of semantic and articulatory loads. These analyses permitted us to identify regions related to word frequency alone, and therefore, likely to be related specifically to activation of phonological word forms. We hypothesized that the increased processing cost of producing lower-frequency words would correlate with activation of the left posterior inferotemporal (IT) cortex, the left posterior superior temporal gyrus (pSTG), and the left inferior frontal gyrus (IFG). Scan-time response latencies demonstrated the expected word frequency effect. Analysis of the fMRI data revealed that activity in the pSTG was modulated by frequency but not word length or concept familiarity. In contrast, parts of IT and IFG demonstrated conjoint frequency and familiarity effects, and parts of both primary motor regions demonstrated conjoint effects of frequency and word length. The results are consistent with a model of word production in which lexical-semantic and lexical-phonological information are accessed by overlapping neural systems within posterior and anterior language-related cortices, with pSTG specifically involved in accessing lexical phonology.