Females and males are highly similar in language performance and cortical activation patterns during verb generation

Abstract

Objective: To test the existence of sex differences in cortical activation during verb generation when performance is controlled for.

Methods: Twenty male and 20 female healthy adults underwent functional magnetic resonance imaging (fMRI) using a covert block-design 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.

Figure 1

Schematic of the ER-VGT. Each trial consists of a 6-second period of MRI silence followed by a 6-second period where we acquire 3fMRI scans (arrows). During the silent period, the subject hears a noun and is visually instructed to covertly “think” of verbs associated with the noun, overtly “say” the associated verbs, or overtly “repeat” the noun and audio is recorded. During the fMRI scan period, the word “STOP” is visually presented for .5 seconds, followed by the word “SCAN” for 5.5 seconds, and we acquire images during the peak of the hemodynamic response (dotted curve) to each preceding stimulus-response event.

Figure 2

Statistical maps for the block-design verb generation task (BD-VGT). Main effects of task in (a) all subjects, (b) males, and (c) females, with warm colors indicating activation greater for covert verb generation than finger tapping and cool colors indicating activation greater for finger tapping than covert genertaion. (d) Direct comparison of males and females for the BD-VGT; activation greater for males in (1) left precentral gyrus (centroid Tailarach coordinates x=-36, y=-15, z=47). Activated regions in statistical maps are significant at p<.05 corrected for multiple voxel comparisons, with nominal Z-scores ranging from -9.5 to -20 (cool colors) or 9.5 to 20 (warm colors). Each statistical map is presented in radiological convention and superimposed on an average T1-weighted image generated from all subjects. The 20 axial slices selected for each display panel range in Talairach coordinates from z=-17 mm (top left) to z=+59 mm (bottom right).

Figure 3

Statistical maps for the ER-VGT isolating noun-verb semantic association. Main effects of task in (a) all subjects, (b) males, and (c) females, with warm colors indicating activation greater for overt generation than repetition and cool colors indicating activation greater for repetition than overt generation. (d) Direct comparison of males and females, with activation greater for males than females in the (1) right superior temporal gyrus/insula (centroid Tailarach coordinates x=39, y=-11, z=-1), (2) left precentral gyrus (centroid Tailarach coordinates x=-51, y=-4, z=35), (3) left middle/superior temporal gyrus (centroid Tailarach coordinates x=-36, y=-56, z=19), and (4) bilateral medial/superior frontal gyrus (centroid Tailarach coordinates x=-2, y=-4, z=59). (e) Controlling for intra-scanner task performance (i.e., verb generation accuracy) when comparing males and females results in greater activation for males in the (1) right head of the caudate extending into the anterior cingulate cortex (centroid Tailarach coordinates x=15, y=22, z=3) and (2) right middle/superior frontal gyrus (BA 9; centroid Tailarach coordinates x=32, y=45, z=27). Activated regions in statistical maps are significant at p<.05 corrected for multiple voxel comparisons, with nominal Z-scores ranging from -9.5 to -20 (cool colors) or 9.5 to 20 (warm colors). Each statistical map is presented in radiological convention and superimposed on an average T1-weighted image generated from all subjects. The 20 axial slices selected for each display panel range in Talairach coordinates from z=-17 mm (top left) to z=+59 mm (bottom right).

Figure 4

Statistical maps for the ER-VGT isolating articulation and auditory processing. Main effects of task in (a) all subjects, (b) males, and (c) females, with warm colors indicating activation greater for overt than covert generation and cool colors indicating activation greater for covert than overt generation. (d) Direct comparison of males and females, with activation greater for females than males in the (1) left cerebellum (centroid Tailarach coordinates x=-13, y=-56, z=-5), and activation greater for males than females in the (2) medial frontal gyrus (centroid Tailarach coordinates x=-2, y=-4, z=55). (e) Controlling for intra-scanner task performance (i.e., verb generation accuracy) when comparing males and females results in greater activation for males in only the (1) medial frontal gyrus. Activated regions in statistical maps are significant at p<.05 corrected for multiple voxel comparisons, with nominal Z-scores ranging from -9.5 to -20 (cool colors) or 9.5 to 20 (warm colors). Each statistical map is presented in radiological convention and superimposed on an average T1-weighted image generated from all subjects. The 20 axial slices selected for each display panel range in Talairach coordinates from z=-17 mm (top left) to z=+59 mm (bottom right).