Amygdalo-fusiform (red) and hippocampo-fusiform (blue) pathways for a typical matched subject pair of an autism participant (a) and control participant (b). The data are from subject pair #7 in Table 1. Pathways are shown in three-dimensional (3D) projection display viewed from above (upper part of a and b), and from the medial side (middle part of a and b). The medial views of the left pathways are inverted so that the left pathway orientations are similar to the right pathways. The 2D anatomical overlays of pathways on I0 images (lower part of a and b) demonstrate the precise anatomical location of pathways with respect to T2-weighted images.

Comparison of the pathway D-min in autism and control groups. a: The left amygdalo-fusiform (AF), left hippocampo-fusiform (HF), and right AF pathways show trends of an increased D-min in the autism group compared with controls (e.g., p =.134 unpaired and .089 paired for the left HF pathway). In contrast, the right HF shows a trend of a decreased D-min in the autism group compared with controls. b: Analysis of laterality (see Methods) shows a strong change in laterality in the HF pathway system (p= .0040 unpaired, .0017 paired) with a loss of lateralization, where laterality ranges from +100% (full left-lateralization) to 0 (no lateralization) to −100% (full right-lateralization). Because two pathway systems (HF and AF) were analyzed for laterality, the Bonferroni-corrected p-value threshold was .05/2 = .025 (to conservatively correct for multiple comparisons). c: Normalization by the whole-brain D-min value reveals that the laterality shift in (b) is predominantly due to a specific decrease in D-min in the right HF pathway in the autism group, compared with controls (p = .038 unpaired and .014 paired, where the corrected p-value threshold is 0 .025 because two HF pathways are tested). This normalization effectively normalizes the pathway measurement by the average whole-brain value for white matter that has an anisotropy above the track-ability threshold. Because the whole-brain D-min in the autism group is increased compared with controls (see text), the decreased D-min in the right HF pathway in (a) is accentuated in (c). In contrast, the trend of increased D-min in the three other pathways in the autism group compared with controls in (a) is suppressed in (c), because the D-min increase in these three pathways is similar to the overall whole-brain increase in D-min. Error bars are ±1SEM. The p values shown in the Fig. are for unpaired t tests (with p values for paired comparisons given in parentheses).

Comparison of the pathway D-max in autism and control groups. a: All four pathways have a trend of increased D-max in the autism group compared with controls. b: Laterality analysis shows a trend toward loss of the normal laterality in the AF pathways in the autism group. Because the trend in (a) affects all four pathways, the effects on laterality are less than for D-min in Figure 2b. c: Normalization by the whole-brain white matter D-max value shows no significant difference in the autism and control groups, indicating that the increases in D-min in (a) are in part reflective of a more global pattern.

Comparison of the HF pathways to Benton facial recognition test scores. For the right HF pathway, which had a reduction in the normalized D-min in the autism group compared with controls in Figure 2c, this reduction is more severe when considering the two subgroups with lower Benton scores (right-most white and gray bars), with p =.014 (one-tailed; corrected threshold .025 for two comparisons for the right HF pathway). Also, within the autism group, the normalized D-min in the right HF pathway was more severely reduced in the lower-Benton subgroup compared with the higher-Benton subgroup (p =.053; one-tailed).

Comparison of the HF pathways to performance IQ (PIQ) scores. Similar to the comparison to Benton scores (Fig. 4), the reduction in the normalized D-min in the autism group compared with controls is more severe in the subgroup that had lower PIQ scores (right-most white and gray bars), with p =.021 (one-tailed; corrected threshold 0.025 as in Fig. 4). Also, within the autism group, the D-min reduction was more severe in the lower-PIQ subgroup compared with the higher-PIQ subgroup (p = .045; one-tailed).