Longitudinal Magnetic Resonance Imaging Study of Cortical Development through Early Childhood in Autism

Cynthia M. Schumann; Cinnamon S. Bloss; Cynthia Carter Barnes; Graham M. Wideman; Ruth A. Carper; Natacha Akshoomoff; Karen Pierce; Donald Hagler; Nicholas Schork; Catherine Lord; Eric Courchesne

doi:10.1523/JNEUROSCI.5714-09.2010

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Figure 1.
Axial section as shown in GWseg, displaying semimanual local threshold segmentation of cerebrum into cerebral gray matter (GM) and cerebral white matter (WM) (a) and resulting tissue classification used by Freesurfer to determine gray/white surface (b).
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Figure 2.
Surface parcellation of cerebral gray (adapted from Desikan et al., 2006).
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Figure 3.
Coronal images indicating parcellation boundaries for lobe regions of cerebral gray.
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Figure 4.
Total cerebral volume (Vol) growth trajectory for males (○) and females (□). Dotted lines represent each subject's volume measurements; solid lines are autistic disorder (red) and typical control (blue) group quadratic growth regression curves. mo, Months.
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Figure 5.
Cerebral gray (left) and white (right) matter volume growth trajectories for males (○) and females (□). Dotted lines represent each subject's volume measurements; solid lines are autistic disorder (red) and typical control (blue) group quadratic growth regression curves.
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Figure 6.
Frontal (left) and temporal (right) gray matter volume growth trajectories for males (○) and females (□). Dotted lines represent each subject's volume measurements; solid lines are autistic disorder (red) and typical control (blue) group quadratic growth regression curves.

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Table 1.

Subject and diagnostic data at final clinical visit

	Autistic disorder (n = 41)		Typical (n = 44)
	Male	Female	Male	Female
Number of subjects	32	9	32	12
Age range at MRI (months)	22–67	26–58	12–63	12–61
Mean age at final clinical visit (months)	49 ± 1	49 ± 10	44 ± 3	46 ± 1
Full-scale IQ	57 ± 18	57 ± 23	111 ± 16	116 ± 15
Verbal IQ	50 ± 19	50 ± 29	112 ± 17	116 ± 15
Performance IQ	63 ± 19	62 ± 21	107 ± 20	115 ± 16
ADI-R Social	18 ± 5	18 ± 6	n/a	n/a
ADI-R NV Comm.	9 ± 3	9 ± 3	n/a	n/a
ADI-R RnR	6 ± 2	5 ± 2	n/a	n/a
Vineland Social	66 ± 9	64 ± 7	97 ± 8	102 ± 15
Vineland Comm.	66 ± 11	62 ± 16	108 ± 11	105 ± 9
Vineland ABC	63 ± 8	64 ± 11	100 ± 10	106 ± 12

n/a, Not applicable; NV Comm., nonverbal communication; RnR, restricted and repetitive.

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Table 2.

Number of successful scans per subject by diagnostic group and the average number and range of months between scans

Numberof scans	Autisticdisorder	Typical	Mean number andrange of monthsbetween scans	Total numberof scans
1	15	12		27
2	16	14	17 (7–25)	60
3	6	8	10 (5–19)	42
4	3	5	8 (3–19)	32
5	0	4	9 (5–20)	20
6	1	1	5 (0–8)	12
Total number of subjects	41	44		193

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Table 3.

Cross-sectional volumetric analyses (ANCOVA with gender and age at MRI scan as covariates) at ∼2.5 years of age for combined sample of males and females with autistic disorder compared with typically developing controls

	Autisticdisorder (n = 41)	Control(n = 44)	Significance(p value)	Percentagedifference
Mean age at MRI (months)	32 ± 9	30 ± 11	0.182
Total cerebrum (cm³)	984 ± 76	920 ± 85	0.018^*	7%
Total white (cm³)	307 ± 32	277 ± 47	0.050^*	10%
Total gray (cm³)	676 ± 59	643 ± 54	0.046^*	5%
Frontal gray (cm³)	232 ± 24	218 ± 19	0.038^*	6%
Temporal gray (cm³)	142 ± 14	131 ± 13	0.008^**	9%
Cingulate gray (cm³)	26 ± 3	24 ± 3	0.097	8%
Parietal gray (cm³)	165 ± 15	160 ± 15	0.289	4%
Occipital gray (cm³)	80 ± 8	78 ± 9	0.225	3%

↵*p ≤ 0.05;
↵**p ≤ 0.01.

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Table 4.

Results of best-fit mixed-effects model analyses in a combined sample of males and females with autistic disorder compared with typically developing controls

Region	Gender	Linear age	Diagnosis	Diagnosis × linear age	Quadratic age	Diagnosis × quadratic age
Total cerebrum	0.003^{^a}	<0.0001^{^a}	0.222	0.546	<0.0001^{^a}	<0.001^{^a}
Total white	0.111	<0.0001^{^a}	0.713	0.264	<0.0001^{^a}	0.051^{^a}
Total gray	0.002^{^a}	<0.0001^{^a}	0.133	0.839	0.002^{^a}	0.073^{^a}
Frontal gray	0.002^{^a}	<0.0001^{^a}	0.027^{^a}
Temporal gray	0.007^{^a}	<0.0001^{^a}	0.008^{^a}	0.972	0.062	0.058^{^a}
Cingulate gray	0.120	<0.0001^{^a}	0.464	0.959	<0.0001^{^a}	0.010^{^a}
Parietal gray	0.053	<0.0001^{^a}	0.647	0.352	0.008^{^a}	0.027^{^a}
Occipital gray	0.001^{^a}	<0.0001^{^a}	0.620		0.009^{^a}

Bold indicates a significant difference between autistic disorder and control.
↵^aSignificant effect.

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Table 5.

Significant differences from best-fit model analyses of males with autistic disorder compared with typically developing controls

Region	Linear age	Diagnosis	Diagnosis × linear age	Quadratic age	Diagnosis × quadratic age
Total cerebrum	<0.0001^{^a}	0.430	0.559	<0.0001^{^a}	0.009^{^a}
Frontal gray	<0.0001^{^a}	0.081^{^a}
Temporal gray	<0.0001^{^a}	0.018^{^a}
Cingulate gray	<0.0001^{^a}	0.970	0.760	<0.0001^{^a}	0.030^{^a}

Bold indicates a significant difference between autistic disorder and control.
↵^aSignificant effect.

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Table 6.

Significant differences from best-fit model analyses of females with autistic disorder compared with typically developing controls

Region	Linear age	Diagnosis	Diagnosis × linear age	Quadratic age	Diagnosis × quadratic age
Total cerebrum	<0.0001^{^a}	0.273	0.029^{^a}	<0.0001^{^a}	0.019^{^a}
Total white	<0.0001^{^a}	0.480	0.001^{^a}	<0.0001^{^a}	0.002^{^a}
Total gray	<0.0001^{^a}	0.230	0.021^{^a}	0.002^{^a}
Frontal gray	<0.0001^{^a}	0.400	0.010^{^a}	0.007^{^a}
Temporal gray	<0.0001^{^a}	0.069^{^a}	0.660	0.008^{^a}	0.078^{^a}
Cingulate gray	<0.0001^{^a}	0.052^{^a}		0.001^{^a}