Supplementary Material for Neural basis of visual attentional orienting in childhood autism spectrum disorders.

fMRI Acquisition Parameters

A high-resolution sagittal T1 weighted scan was acquired on a Siemens Magnetom TrioTim 3T MRI scanner using a 3D MGH_MPRAGE sequence with a scan time of 8:05 min and the following parameters: TR = 2530 ms, TE = 3.5 ms, 256 x 256 mm FOV, 176 mm slab with 1mm thick slices, 256 X 256 X 176 matrix (effective resolution is 1.0 mm3), 1 excitation and a 7 degree flip angle. Functional images were acquired using a T2*-sensitive gradient EPI sequence with the following parameters: TR = 2500ms, TE = 30ms, 192x192mm FOV, and 90 degree flip angle. Forty-three 3mm thick slices were acquired in the axial plane in an interleaved descending sequence for 142 time points (the first 2 TRs were included for signal stabilization and discarded from analysis).

Imaging preprocessing

Functional images were analyzed using SPM8 and its custom toolboxes (Wellcome Department of Cognitive Neurology, London, UK). Subjects with movement greater than 3mm in the x, y, or z directions were excluded from analysis. Additionally, affine framewise displacement was measured using the ArtRepair toolbox for SPM; subjects with more than 20% of volumes exceeding 0.5mm of frame-to-frame displacement were excluded from further analysis. Images were slice-time and motion corrected, normalized and smoothed with an 8mm FWHM Gaussian kernel. Regressors for both framewise displacement and individual volumes with affine framewise displacement above 0.5mm were included. Percentage of frames above 0.5 mm motion did not differ between groups, t(31.83)=1.33, p = .192; ASD mean frames removed: 18.04, SD: 16.00; CON mean frames removed: 13.57, SD: 9.29.

Equal trial number confirmatory one-sample t-tests

The current task was designed to parallel dot-probe tasks in which the number of neutral trials (18) was equal to congruent and incongruent trials with left and right targets (18 left +18 right = 36 congruent, 36 incongruent). As the current analysis combined congruent and incongruent trials (72 total Biased trials), it was necessary to ensure that results were not based on unequal numbers of Biased and Neutral trials. To do this, separate One-sample t-tests were performed contrasting the 18 Neutral trials with the first 18 Biased trials of each run, and were thresholded at a less stringent level (cluster extent = 50 voxels, uncorrected p < .01) to see any trend-level data. In control children, activation was greater in Biased than Neutral trials in one cluster comprising the right precentral and superior frontal gyrus, while activation was greater in Neutral than Biased in one cluster comprising the left precentral gyrus (Supplementary table 2). In ASD children, no regions showed greater activation in the Biased than Neutral trials. However, 10 regions showed greater activation in the Neutral than Biased trials, including bilateral anterior cingulate, bilateral precuneus, right posterior cingulate left insula, left inferior occipital gyrus, right middle occipital gyrus, right lingual gyrus, right cerebellum, and left pre-and postcentral gyrus, and left paracentral lobule. These findings parallel those of the full task design, and confirm that findings of greater activation to Neutral than Biased trials in ASD is not due to unequal number of trials.

Supplementary Table 1

Regions of activation for the Biased (Bias) vs. Neutral (Neut) trial contrast separately for ASD and control (CON) groups.

Contrast / Region / BA / X / Y / Z / Z value / Voxels
CON
Bias > Neut / R Precentral gyrus / 4 / 36 / -25 / 64 / 4.25 / 358
R Precentral gyrus / 6 / 42 / -10 / 61 / 3.59
R Postcentral gyrus / 1 / 57 / -16 / 52 / 3.35
R Postcentral gyrus / 2 / 33 / -28 / 49 / 3.31
R Precentral gyrus / 3 / 27 / -28 / 76 / 2.97
R Mid Cingulate gyrus / 5 / 15 / -22 / 46 / 2.86
R Precentral gyrus / 1 / 21 / -28 / 79 / 2.82
L Lingual gyrus / 19 / -9 / -61 / -2 / 3.71 / 130
R Calcarine / 31 / 12 / -67 / 13 / 3.04
L Calcarine / 30 / 3 / -67 / 10 / 2.91
L Postcentral gyrus / 6 / -51 / -4 / 19 / 3.59 / 63
L Postcentral gyrus / 2 / -39 / -25 / 40 / 2.78
L Postcentral gyrus / 40 / -45 / -22 / 31 / 2.66
Neut > Bias / No Regions
ASD
Bias > Neut / No Regions
Neut > Bias / R Inf Frontal gyrus / 45 / 30 / 35 / 7 / 4.30 / 319
R Inf Orbitofrontal gyrus / 47 / 48 / 35 / -11 / 4.00
R Caudate / 9 / 23 / -2 / 3.47
R Ant Cingulate gyrus / 32 / 6 / 35 / -8 / 3.40
R Med Orbitofrontal gyrus / 11 / 9 / 47 / -14 / 2.89
L Caudate / -6 / 17 / -2 / 2.87
R Cerebellum 1 / 39 / -73 / -38 / 3.54 / 148
R Cerebellum 2 / 36 / -79 / -35 / 3.47
R Cerebellum 6 / 24 / -73 / -23 / 3.14
R Mid Temporal gyrus / 21 / 36 / -52 / 16 / 3.35 / 69
R Inf Parietal lobule / 40 / 36 / -34 / 28 / 3.14
R Angular gyrus / 38 / 39 / -52 / 31 / 3.11

Supplementary Table 2

Regions of activation for the Biased (Bias) vs. Neutral (Neut) trial contrast separately for ASD and control (CON) groups with equal number Bias and Neut trials.

Contrast / Region / BA / X / Y / Z / Z value / Voxels
CON
Bias > Neut / R Precentral Gyrus / 6 / 42 / -4 / 58 / 2.94 / 57
R Superior Frontal Gyrus / 6 / 33 / -7 / 67 / 2.79
Neut > Bias / L Precentral Gyrus / 4 / -33 / -28 / 61 / 4.7 / 240
ASD
Bias > Neut / No Regions
Neut > Bias / L Inferior Occipital Gyrus / 17 / -27 / -97 / -8 / 5.19 / 276
R Lingual Gyrus / 18 / 24 / -97 / -5 / 4.42 / 94
R Middle Occipital Gyrus / 18 / 24 / -85 / 1 / 3.04
L Anterior Cingulate / 32 / -12 / 44 / -8 / 4.32 / 1677
R Anterior Cingulate / 32 / 6 / 47 / -2 / 4.16
L Precuneus / 31 / -9 / -58 / 25 / 4.27 / 1013
R Posterior Cingulate / 31 / 6 / -55 / 22 / 3.96
R Precuneus / 31 / 6 / -64 / 25 / 3.94
R Cerebellum / * / 21 / -79 / -32 / 4.05 / 234
L Postcentral Gyrus / 3 / -33 / -31 / 55 / 3.88 / 162
L Precentral Gyrus / 4 / -36 / -25 / 70 / 3.01
R Superior Frontal Gyrus / 6 / 15 / 26 / 49 / 3.76 / 375
L Cingulate Gyrus / 32 / -6 / 11 / 34 / 3.56 / 79
R Cingulate Gyrus / 24 / 9 / 5 / 37 / 2.83
L Precentral Gyrus / 6 / -36 / -7 / 31 / 3.23 / 125
L Insula / 13 / -42 / 2 / 10 / 2.75
L Cingulate Gyrus / 24 / -15 / -1 / 34 / 2.64
L Paracentral Lobule / 6 / -12 / -28 / 46 / 3.05 / 54

Supplementary Figure 1. Examples of Biased (A) and Neutral (C) stimuli, and salience maps for each (B and D respectively) as calculated by Saliency Toolbox. Separate maps are created for color, intensity, and orientation visual channels, as well as an overall saliency map combining the influence of each channel on total salience.

Supplementary Figure 2. A between-groups contrast of Biased > Neutral was performed on subjects showing a behavioral positive attention bias. Results were similar to the same contrast using the full group, though the cluster in the right OFG fell below significance.