Objective To test the existence of sex differences in cortical activation during verb generation when performance is controlled for. Methods 20 male and 20 female healthy adults underwent fMRI using a covert verb generation task (BD-VGT) and its event-related version (ER-VGT) that allowed for intra-scanner recordings of overt responses. Task-specific activations were determined using the following contrasts: BD-VGT covert generation>finger-tapping; ER-VGT overt generation>repetition; ER-VGT overt>covert generation. Lateral cortical regions activated during each contrast were used for calculating language lateralization index scores. Voxelwise regressions were used to determine sex differences in activation, with and without controlling for performance. Each brain region showing male/female activation differences for ER-VGT overt generation>repetition (isolating noun-verb association) was defined as a region of interest (ROI). For each subject, the signal change in each ROI was extracted, and the association between ER-VGT activation related to noun-verb association and performance was assessed separately for each sex. Results Males and females performed similarly on language assessments, had similar patterns of language lateralization, and exhibited similar activation patterns for each fMRI task contrast. Regression analysis controlling for overt intra-scanner performance either abolished (BD-VGT) or reduced (ER-VGT) the observed differences in activation between sexes. The main difference between sexes occurred during ER-VGT processing of noun-verb associations, where males showed greater activation than females in the right middle/superior frontal gyrus (MFG/SFG) and the right caudate/anterior cingulate gyrus (aCG) after controlling for performance. Better verb generation performance was associated with increased right caudate/aCG activation in males and with increased right MFG/SFG activation in females. Conclusions Males and females exhibit similar activation patterns during verb generation fMRI, and controlling for intra-scanner performance reduces or even abolishes sex differences in language-related activation. These results suggest that previous findings of sex differences in neuroimaging studies that did not control for task performance may reflect false positives.

Behavioral studies have shown that verbal information is better retained when it is self-generated rather than read (learned passively). We used fMRI and a paired associates task to examine brain networks underlying self-generated memory encoding. Subjects were 49 healthy English speakers ages 19–62 (30 female). In the fMRI task, related word pairs were presented in a “read” condition, where subjects viewed both words and read the second word aloud, or a “generate” condition, where the second word was presented with only the first letter and the subject was required to generate the word. Thirty word pairs were presented in each condition. After the fMRI scan, words that were read or generated were presented, each with two foils, in a forced-choice recognition task. On the recognition post-test, words from the “generate” condition were more correctly recognized than from the “read” condition (80.0% for generated words versus 72.0% for read words; t(48) = 5.17, p < 0.001). FMRI revealed increased activation for generate>read in inferior/middle frontal gyri bilaterally (L>R), anterior cingulate, and caudate nucleus and the temporo-parietal-occipital junction bilaterally. For the “read” condition, better subsequent memory performance across individual subjects was positively correlated with activation in the cuneus bilaterally. In the “generate” condition, better subsequent memory performance was positively correlated with activation in the left superior temporal gyrus. These results suggest that self-generation improves memory performance, that enhanced cortical activation accompanies self-generated encoding, and that recruitment of a specific brain network underlies self-generated encoding. The findings may have implications for the development of procedures to enhance memory performance.

Verbal information is better retained when it is self-generated rather than when it is received passively. The application of self-generation procedures has been found to improve memory in healthy elderly and in individuals with impaired cognition. Overall, the available studies support the notion that active participation in verbal encoding engages memory mechanisms that supplement those used during passive observation. Thus, the objective of this study was to investigate the age-related changes in the neural mechanisms involved in the encoding of paired-associates using a self-generation method that has been shown to improve memory performance across the lifespan. Subjects were 113 healthy right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18–76, native speakers of English with no history of neurological or psychiatric disorders. Subjects underwent fMRI at 3 T while performing didactic learning (“read”) or self-generation learning (“generate”) of 30 word pairs per condition. After fMRI, recognition memory for the second word in each pair was evaluated outside of the scanner. On the post-fMRI testing more “generate” words were correctly recognized than “read” words (p < 0.001) with older adults recognizing the “generated” words less accurately (p < 0.05). Independent component analysis of fMRI data identified task-related brain networks. Several components were positively correlated with the task reflecting multiple cognitive processes involved in self-generated encoding; other components correlated negatively with the task, including components of the default-mode network. Overall, memory performance on generated words decreased with age, but the benefit from self-generation remained consistently significant across ages. Independent component analysis of the neuroimaging data revealed an extensive set of components engaged in self-generation learning compared with didactic learning, and identified areas that were associated with age-related changes independent of performance.