Magnitude of Activation During Auditory Task
Activation maps for control and autism populations during the auditory language task is shown in . All subjects showed activated clusters in expected language regions (Wernicke’s area, Broca’s area, lateral premotor cortex, supplementary motor area, left dorsolateral prefrontal cortex), when thresholded at acceptable FDR p < 0.05. Population activation maps showed remarkable similarity in spatial distribution of activation, with similar T-scores and spatial coordinates of local maxima in core language regions (). A few notable differences are seen. There is a focus of activation in the left posterior insula much greater in the control map (, white arrow), and activation in the right Wernicke’s homolog extends further posterior in the autism map than in the control map (, black arrows). A trend towards increased activation in right lateral premotor cortex in the autism map (, black arrow) was not statistically significant in our sample. We detect no significant difference in magnitude of auditory stimulus responses in primary auditory cortical regions between groups. Cerebellar activation was also noted for most subjects, but the infratentorial brain was not consistently included in the field of view for all subjects and does not appear on activation maps.
Activation of core auditory language regions
Differences in Auditory and Visual Task Activation
The visual task showed similar spatial distribution of language activation, with additional posterior parietal, lateral temporo-occipital, and visual cortical areas. The difference between auditory and visual task activation, thresholded at FDR p<0.05, is shown in blue in , rendered on MNI template brain image, with remaining auditory task activation from all subjects shown in red. The auditory task showed significant increases in activation over the visual task in bilateral superior temporal gyrus corresponding to primary auditory cortex, with additional activation of left greater than right posterior insula. No significant posterior insular activation was seen during visual task.
Differences Between Populations in Auditory Task Activation
To compare autism and control populations, a second-level, 2-sample t-test design was performed and control > autism and autism > control contrasts were evaluated. illustrates control > autism contrast, shown for acceptable FDR p<0.05. Activity was seen for this contrast only in the left posterior insula, with peak activity at MNI coordinates x= −39, y= −28, z= 16, and T-score of 5.7, corresponding to FDR corrected p-value of 0.0087. No other areas of significantly differential activation were seen.
Figure 3 Areas of greater activation for control than autism subjects for auditory language task. A. Control > autism activation for p<0.05, FDR. Colorbar shows T-score. B. BOLD time series data for cluster shown above for entire auditory language (more ...)
Autism > control contrast demonstrated a cluster in right posterior middle temporal gyrus, along the posterior inferior aspect of Wernicke’s homolog at MNI coordinates x= 48, y= −55, z= 4, with T-score 4.1. To further evaluate this region, a small volume correction was performed by limiting evaluation to right Wernicke’s homolog, given our a priori hypothesis that autistic subjects would show increased right-hemispheric activation of language regions. We limited evaluation by searching within a 2 cm diameter sphere that enclosed all significantly activated voxels in right Wernicke’s homolog region on the group activation map obtained from all subjects. With this correction, this cluster was significant at p=0.004, FDR. No other foci of significantly different activation were seen for autism > control contrast.
Laterality Indices in Control and Autism Populations
To test for significant differences in language lateralization between autism and control samples, we identified receptive language clusters in the left and right hemisphere for each subject. Receptive language regions were selected because our task was designed primarily for receptive language activation.
Left and right hemispheric clusters in Wernicke’s region and homolog were identified for each subject after masking out the primary auditory cortex using auditory > visual contrast. Laterality indices are shown in , with population statistics listed in . There was significantly greater relative activation of right-sided language regions in the autism group that was out of proportion to slight differences in hand preference as measured by Edinburgh Handedness Inventory, indicating that language lateralization is not merely a consequence of known population biases towards decreased right-handedness in autism. Moreover, these differences in laterality were observed in data for which variance associated with hand preference was already included as a regressor in the group-level analysis.
Figure 4 Hand preference and language laterality for autism and control subjects. Histograms show number of subjects exhibiting scores between −100 and 100 (Edinburgh Handedness Inventory) or between −1 and 1 (fMRI laterality index), where 100 (more ...)
Effect of Age, Verbal IQ and Standardized Language Scores on Activation
Four covariables were included in the regression when evaluating group-level activation: age, handedness, verbal IQ, and CELF-3 receptive language function score. No significant foci of differential activation were associated with handedness. Increased proficiency on receptive language testing (CELF-3) was associated with increased activation in the posterior left Wernicke’s area (, red), significant at p<0.05, FDR. Increased verbal IQ scores were associated with a trend toward activation in bilateral posterior inferior frontal gyrus (left Broca’s area and right hemispheric homolog), right putamen, left dorsomedial prefrontal cortex, left lateral premotor cortex, and right anterior temporal pole (, blue). These clusters were all significant at p<0.001, uncorrected, but did not survive FDR correction at p=0.05. MNI coordinates of activation associated with CELF-3 and verbal IQ tests are listed in . With younger age, activation was seen in the region of bilateral nucleus accumbens, with peak activity at x= −3, y= −1, z= −5, T-score = 4.8, corresponding to acceptable FDR p-value of 0.031. This cluster is shown in . No significant differential activation was associated with older age, lower verbal IQ score, or lower CELF-3 score.
Figure 5 Associations between auditory language activation and covariables for all subjects. A. Activity associated with higher receptive language (CELF-3) scores (red, p<0.05, FDR) and higher verbal IQ (blue, p<0.001, uncorrected). B. Activity (more ...)
MNI coordinates of increased activation associated with standardized test scores.