Language assessment and behavioral performance
Prior to MRI scanning, all subjects received a battery of language assessments. Performance variables are summarized in . As expected, HC subjects performed significantly better than LMCA stroke subjects on all language assessments, on BD-VGT post-scan noun recognition, and on all ER-VGT intra-scanner behavioral measures (all p<0.05).
Functional MRI activation and language lateralization
GLM analysis was performed for each task to determine task-related activation [47
]. The following describes specific fMRI activation and language-related lateralization patterns within each group for each GLM contrast in greater detail. Brain regions showing significant activation in the z-score maps are listed in . Lateralization index (LI) scores, calculated using anatomical ROIs of frontal and posterior language areas used previously [12
], and lateralization categories are summarized in .
Activation foci (centroid Talairach coordinates) and Brodmann’s Areas (BAs) for the activated brain regions for the group z-score maps shown in and .
Lateralization index scores and lateralization for the frontal and posterior anatomically-defined regions of interest for the 32 healthy and 16 LMCA stroke subjects performing the verb generation tasks.
Group z-score maps for the BD-VGT contrast isolating activation related to covert verb generation () revealed that HC followed a typical pattern of left>right frontal-temporal and left parietal activation, as well as activation in the SFG/CG. This is similar to the pattern shown in previous studies utilizing this task [28
]. HC activation maps for the BD-VGT contrast are displayed for both a corrected p
<0.05 () and an uncorrected p
<0.001 (, upper panel); a less stringent threshold was also used due to the possibility of reduced signal to noise in data obtained from elderly or diseased individuals [55
]. LMCA stroke subjects showed activation only at the lower threshold (, lower panel) where they exhibited BD-VGT activation in the right IFG and more superior regions of the left IFG/MFG, the SFG, and bilateral (right>left) temporal activation. The average LI scores for HC were significantly greater than for stroke subjects for the posterior anatomical ROI (p
=0.0053), but not for the frontal ROI (p
=0.13). These lateralization patterns were significantly different between groups for the posterior ROI (p
=0.0028) but not for the frontal ROI (p
=0.055). Both the average LI scores and pattern of lateralization correspond well with the group activation patterns observed for the BD-VGT.
ER-VGT activation related to processing noun-verb semantic associations in HC occurred in bilateral (left>right) IFG and MFG, bilateral (left>right) MTG extending into STG, medially-located SFG/CG, posterior CG and in cerebellar, visual, and left temporo-parietal regions (, upper panel). In contrast, stroke subjects exhibited only three clusters of significant activation located in the left MTG, medially in the SFG/CG, and a more superior region of the left MFG (, lower panel). For the frontal ROI, the average LI was significantly greater in HC than stroke subjects (p=0.0002), and the pattern of lateralization was significantly different between groups (p=0.00015) with the stroke subjects exhibiting a shift towards more symmetric language-related activation. These differences were not evident for the posterior ROI in either LI (p=0.25) or lateralization pattern (p=0.78).
Figure 3 Group z-score maps for the event-related version of the verb generation task (ER-VGT). Brain regions show increased activation related to (A) processing noun-verb semantic associations and (B) articulation and auditory processing in healthy (top panel) (more ...)
ER-VGT activation related to articulation and auditory processing were predominantly symmetrical for HC, particularly in insular and motor cortices and in temporal, visual, cerebellar, and subcortical regions (; upper panel). ER-VGT activation in stroke subjects occurred largely in the unaffected hemisphere including the right insular cortex, right>left motor cortex, right STG, and right thalamus (; lower panel). We also observed bilateral activation in the cerebellum and visual cortex for stroke subjects. The average LI scores were similar between HC and stroke subjects for the frontal ROI (p=0.15), and there was no group difference in the lateralization pattern for either the frontal or posterior ROI (p=0.43 and p=0.11, respectively). However, there was a trend towards a significant group difference for the posterior ROI (p=0.052), with the more negative mean LI for stroke subjects reflecting the right STG activation in their group activation map compared to the bilateral STG activation observed in healthy subjects.
Relationships between functional ROI activation and intra-scanner performance
We found significant positive associations between verb generation performance and fMRI activation during ER-VGT semantic processing for stroke subjects in the left MFG (r=0.51, p=0.042) and in the more medially located SFG/CG (r=0.57, p=0.020), but not in the left MTG (r=0.26, p=0.32). Conversely, the HCs exhibited a significant relationship between verb generation performance and fMRI activation related to semantic processing in the left MTG (r=0.38, p=0.031), but not in the left MFG (r=0.17, p=0.35) or the SFG/CG (r=0.038, p=0.84). There were no significant associations in either group between verb generation performance and ER-VGT activation related to articulation and auditory processing in the right insula/IFG or right STG (all p>0.1).
Associations between lesion size and performance
Lesion volume had significant negative associations with performance on the Controlled Oral Word Association Test (r=−0.63, p=0.0092) and the Semantic Fluency Test (r=−0.53, p=0.033), and showed a trend towards a negative association with ER-VGT verb generation performance (r=−0.45, p=0.081). However, lesion volume was not significantly associated with performance on the post-fMRI noun recognition test (r=−0.39, p=0.13), the Complex Ideation subtest of the Boston Diagnostic Aphasia Examination, the Peabody Picture Vocabulary Test (r=0.12, p=0.66) and the Boston Naming Test (r=−0.31, p=0.24).