1. Naama Barnea-Goraly, MD; Linda J. Lotspeich, MD; Allan L. Reiss, MD 認知所 碩一 陳彥州 1

2.  Autism is a neurobiological condition with a strong genetic component.  Characteristics : 1) Impairments in Social interaction and communication. 2) Restricted, repetitive of behavior. 2

3.  Autistics have common problems with their siblings. − Brain function 、 behavioral and immune profiles.  Recent diffusion tensor imaging (DTI) studies have indicated that white matter (WM) structure is aberrant in autism. 3

4. 1) Compared WM structure in autism 、 siblings and controls. 2) WM structure in autism is correlated with autism symptoms. 4

5.  ASSESSMENTS — Child Behavior Checklist → unaffected siblings & control subjects. — Autism Diagnostic Interview–Revised (ADI-R) & the Autism Diagnostic Observation Schedule (ADOS) → subjects with autism. — Wechsler Scale of Intelligence → all subjects. 5

6.  A sample of 37 children : ― 13 subjects with autism, 13 of their unaffected siblings, and 11 controls. ― Controls were intelligence quotient- matched to the unaffected siblings. ― All groups were age matched. 6

7.  GE-Signa 1.5-Tesla scanner 7

8.  Imaging parameters : ― FOV=24 cm; matrix size=128 ×128; TE=106 ms; TR=6000 ms. ― 19 axial-oblique slices; slice thickness=5 mm; skip=1.5 mm. ― Diffusion gradient δ =32 ms ; b value=900 s/mm. ― Diffusion was measured along 6 noncollinear directions: XY, XZ, YZ, −XY, −XZ and −YZ. 8

9. 9 ( ) ( )  Eigenvector :  Eigenvalue :

10.  Main Outcome Measure: ― (1)Fractional anisotropy (FA) 、 (2)axial and (3)radial diffusivities. ― Behavioral correlation analyses were conducted using the (4)ADI-R and (5)ADOS subscales scores v.s FA values in the autism group. 10

11.  Fractional anisotropy(FA) : − 代表一個體素非等項性擴散的程度。  Axial diffusivity = the largest diffusivity( λ1). − To represent fiber coherence.  Radial diffusivity = the mean of diffusivities (λ2+λ3/2). − To represent fiber integrity and myelinization. 11

12. 1) Compared with the control group, both the autism and sibling groups had widespread, significantly reduced WM FA values. 2) Within regions of reduced FA, significant reductions also in axial diffusivity, but not radial diffusivity, were observed. 3) There were no significant differences in white matter structure between the autism and sibling groups. 4) There were no significant correlations between autism symptomatology and white matter FA. 12

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14.  Individuals With Autism v.s Unaffected Siblings ― There were no significant FA differences in the whole brain voxelwise t test analysis. 14

15.  BEHAVIORAL CORRELATIONS ― Behavioral correlation analyses also were conducted using FA values and the ADI-R and ADOS subscale scores. ― No significant correlations were observed between these behavioral measures and FA values. 15

16.  Significant WM differences from controls included medial prefrontal, and superior temporal regions, the temporo-parietal junctions. − This regions that have implicated in social Communication, theory of mind, and face processing. 16

17.  Superior longitudinal fasciculus(SLF): SLF is a major intrahemispheric fiber that traverses the frontal, parietal, and temporal lobes. SLFII connects Brodmann areas 6,8Ad,and46. ― That implicated in social deficits 、 spatial awareness and the orienting 、 spatial working memory. SLF III important in language development. 17

18.  Reducing axial diffusivity with no change in radial diffusivity between the control group and subjects with autism or their unaffected siblings. − WM aberrations in autism may arise primarily from changes in fiber coherence and not changes in myelination. 18

19.  Their findings suggest that white matter structure may represent a marker of genetic risk for autism or vulnerability to development of this disorder. 19

20. Thanks for your attention 20

21.  EXCLUSION CRITERIA ― Child Behavior Checklist factor score greater than 1.5 SD from the mean and a full scale IQ less than 80. ― Didn’t meet threshold scores for autistic disorder on the ADI-R and ADOS. ― Couldn’t tolerate the scanning experience. 21

22.  Design: ― Cross-sectional, case-control, voxel-based, whole-brain DTI analysis using Tract-Based Spatial Statistics(TBSS). 22

23.  Individuals With Autism v.s Control Subjects ― FA values significant widespread reductions compared with control subjects. ― Significant differences between autism and controls in axial diffusivity. ― No significant differences were seen between these groups in radial diffusivity. 23

24.  Unaffected Siblings v.s Controls ― FA values were significantly reduced in the unaffected siblings compared with control subjects. ― Significant differences in axial diffusivity were observed only in the right hemisphere. ― No differences in radial diffusivity were observed between these groups. 24