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Michel Godel
Universite de Geneve Faculte de Medecine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9789-3540
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the sharpness of the gray-white matter boundary is decreased in adults with ASD. To determine how the gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index called the gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.
Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3).
Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.
Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but the limited size of our sample warrants further replication in independent and larger samples.
Conclusion: These results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread areas. Early onset of symptoms constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.
Keywords
Autism Spectrum Disorder, Sibling risk, Toddlers, Neurodevelopment, Neuroimaging, FreeSurfer
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This is a list of supplementary files associated with this preprint. Click to download.
- S1.jpg
Additional File 1: Figure S1 A. Clusters with a significant effect of time on gray-white matter contrast (GWC) in the HR-TD group. Clusters with cluster-wise P-value (CWP) < 0.05 only are displayed. Color code corresponds to P-value of the vertex with the maximal P-value (Pvm) of each cluster. B. On the right are plotted for each hemisphere the individual GWC rates of change (ΔGWC) within each significant cluster (one per hemisphere). We found no significant difference between both clusters (paired T-test, p=0.15).
- S1.jpg
Additional File 1: Figure S1 A. Clusters with a significant effect of time on gray-white matter contrast (GWC) in the HR-TD group. Clusters with cluster-wise P-value (CWP) < 0.05 only are displayed. Color code corresponds to P-value of the vertex with the maximal P-value (Pvm) of each cluster. B. On the right are plotted for each hemisphere the individual GWC rates of change (ΔGWC) within each significant cluster (one per hemisphere). We found no significant difference between both clusters (paired T-test, p=0.15).
- S2.jpg
Additional File 2: Figure S2 Results displayed on Fig 3 (Association between GWC at age 12-24 months and symptom severity at 18 months of age) with individual mean GWC values displayed for each significant cluster in function of ADOS calibrated severity score (CSS) (upper-side graphs) and diagnostic outcome group (down-side graphs). A. Results for clusters with significant correlation between GWC and 18-mo ADOS CSS. B. Clusters with significant correlation between GWC and 36-mo ADOS CSS. *p<0.05 **p<0.01 ***p<0.001. mGWC: mean GWC between two scan acquisitions.
- S2.jpg
Additional File 2: Figure S2 Results displayed on Fig 3 (Association between GWC at age 12-24 months and symptom severity at 18 months of age) with individual mean GWC values displayed for each significant cluster in function of ADOS calibrated severity score (CSS) (upper-side graphs) and diagnostic outcome group (down-side graphs). A. Results for clusters with significant correlation between GWC and 18-mo ADOS CSS. B. Clusters with significant correlation between GWC and 36-mo ADOS CSS. *p<0.05 **p<0.01 ***p<0.001. mGWC: mean GWC between two scan acquisitions.
- S3.jpg
Additional File 3: Figure S3 Results displayed on Fig 5 (Association between symptom severity at 18 months of age andn GWC rate of change (ΔGWC) between 12 and 24 months of age) with individual ΔGWC displayed for each cluster in function ADOS calibrated severity score (CSS) (upper-side graph) and diagnostic outcome group (down-side graph). *p<0.05 **p<0.01 ***p<0.001.
- S3.jpg
Additional File 3: Figure S3 Results displayed on Fig 5 (Association between symptom severity at 18 months of age andn GWC rate of change (ΔGWC) between 12 and 24 months of age) with individual ΔGWC displayed for each cluster in function ADOS calibrated severity score (CSS) (upper-side graph) and diagnostic outcome group (down-side graph). *p<0.05 **p<0.01 ***p<0.001.
- S4.jpg
Additional File 4: Figure S4 Association between cortical thickness at age 12-24 months (computed as mean CT between the two scan acquisitions) and diagnostic outcome at 36 months of age (HR-ASD or HR-TD). The single cluster with significantly smaller CT in HR-ASD compared to HR-TD (CWP < 0.05) is displayed. We found no significant cluster in the right hemisphere. Color code corresponds to P-value of the vertex with maximal P-value (Pvm) of the displayed cluster (Table 2). On the right, individual CT values are displayed in function of diagnosis outcome for the displayed cluster. Same values are further plotted on the right in function of HR-TD subgroups (LOA and EOA). Results of comparisons between LOA/EOA and HR-TD and between HR-ASD and HR-TD are displayed on the same graph. *p<0.05. CWP: cluster-wise P-value; mCT: Mean cortical thickness between the two scan acquisitions; EOA: Early onset ASD; LOA: Late onset ASD
- S4.jpg
Additional File 4: Figure S4 Association between cortical thickness at age 12-24 months (computed as mean CT between the two scan acquisitions) and diagnostic outcome at 36 months of age (HR-ASD or HR-TD). The single cluster with significantly smaller CT in HR-ASD compared to HR-TD (CWP < 0.05) is displayed. We found no significant cluster in the right hemisphere. Color code corresponds to P-value of the vertex with maximal P-value (Pvm) of the displayed cluster (Table 2). On the right, individual CT values are displayed in function of diagnosis outcome for the displayed cluster. Same values are further plotted on the right in function of HR-TD subgroups (LOA and EOA). Results of comparisons between LOA/EOA and HR-TD and between HR-ASD and HR-TD are displayed on the same graph. *p<0.05. CWP: cluster-wise P-value; mCT: Mean cortical thickness between the two scan acquisitions; EOA: Early onset ASD; LOA: Late onset ASD
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Michel Godel
Universite de Geneve Faculte de Medecine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9789-3540
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The most recent version of this article is available here.
No community comments so far
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Version 1
Posted 02 Dec, 2020
No comments provided
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Comments: 0
PDF Downloads: ...
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Subject Areas
Psychology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the sharpness of the gray-white matter boundary is decreased in adults with ASD. To determine how the gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index called the gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.
Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3).
Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.
Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but the limited size of our sample warrants further replication in independent and larger samples.
Conclusion: These results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread areas. Early onset of symptoms constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- S1.jpg
Additional File 1: Figure S1 A. Clusters with a significant effect of time on gray-white matter contrast (GWC) in the HR-TD group. Clusters with cluster-wise P-value (CWP) < 0.05 only are displayed. Color code corresponds to P-value of the vertex with the maximal P-value (Pvm) of each cluster. B. On the right are plotted for each hemisphere the individual GWC rates of change (ΔGWC) within each significant cluster (one per hemisphere). We found no significant difference between both clusters (paired T-test, p=0.15).
- S1.jpg
Additional File 1: Figure S1 A. Clusters with a significant effect of time on gray-white matter contrast (GWC) in the HR-TD group. Clusters with cluster-wise P-value (CWP) < 0.05 only are displayed. Color code corresponds to P-value of the vertex with the maximal P-value (Pvm) of each cluster. B. On the right are plotted for each hemisphere the individual GWC rates of change (ΔGWC) within each significant cluster (one per hemisphere). We found no significant difference between both clusters (paired T-test, p=0.15).
- S2.jpg
Additional File 2: Figure S2 Results displayed on Fig 3 (Association between GWC at age 12-24 months and symptom severity at 18 months of age) with individual mean GWC values displayed for each significant cluster in function of ADOS calibrated severity score (CSS) (upper-side graphs) and diagnostic outcome group (down-side graphs). A. Results for clusters with significant correlation between GWC and 18-mo ADOS CSS. B. Clusters with significant correlation between GWC and 36-mo ADOS CSS. *p<0.05 **p<0.01 ***p<0.001. mGWC: mean GWC between two scan acquisitions.
- S2.jpg
Additional File 2: Figure S2 Results displayed on Fig 3 (Association between GWC at age 12-24 months and symptom severity at 18 months of age) with individual mean GWC values displayed for each significant cluster in function of ADOS calibrated severity score (CSS) (upper-side graphs) and diagnostic outcome group (down-side graphs). A. Results for clusters with significant correlation between GWC and 18-mo ADOS CSS. B. Clusters with significant correlation between GWC and 36-mo ADOS CSS. *p<0.05 **p<0.01 ***p<0.001. mGWC: mean GWC between two scan acquisitions.
- S3.jpg
Additional File 3: Figure S3 Results displayed on Fig 5 (Association between symptom severity at 18 months of age andn GWC rate of change (ΔGWC) between 12 and 24 months of age) with individual ΔGWC displayed for each cluster in function ADOS calibrated severity score (CSS) (upper-side graph) and diagnostic outcome group (down-side graph). *p<0.05 **p<0.01 ***p<0.001.
- S3.jpg
Additional File 3: Figure S3 Results displayed on Fig 5 (Association between symptom severity at 18 months of age andn GWC rate of change (ΔGWC) between 12 and 24 months of age) with individual ΔGWC displayed for each cluster in function ADOS calibrated severity score (CSS) (upper-side graph) and diagnostic outcome group (down-side graph). *p<0.05 **p<0.01 ***p<0.001.
- S4.jpg
Additional File 4: Figure S4 Association between cortical thickness at age 12-24 months (computed as mean CT between the two scan acquisitions) and diagnostic outcome at 36 months of age (HR-ASD or HR-TD). The single cluster with significantly smaller CT in HR-ASD compared to HR-TD (CWP < 0.05) is displayed. We found no significant cluster in the right hemisphere. Color code corresponds to P-value of the vertex with maximal P-value (Pvm) of the displayed cluster (Table 2). On the right, individual CT values are displayed in function of diagnosis outcome for the displayed cluster. Same values are further plotted on the right in function of HR-TD subgroups (LOA and EOA). Results of comparisons between LOA/EOA and HR-TD and between HR-ASD and HR-TD are displayed on the same graph. *p<0.05. CWP: cluster-wise P-value; mCT: Mean cortical thickness between the two scan acquisitions; EOA: Early onset ASD; LOA: Late onset ASD
- S4.jpg
Additional File 4: Figure S4 Association between cortical thickness at age 12-24 months (computed as mean CT between the two scan acquisitions) and diagnostic outcome at 36 months of age (HR-ASD or HR-TD). The single cluster with significantly smaller CT in HR-ASD compared to HR-TD (CWP < 0.05) is displayed. We found no significant cluster in the right hemisphere. Color code corresponds to P-value of the vertex with maximal P-value (Pvm) of the displayed cluster (Table 2). On the right, individual CT values are displayed in function of diagnosis outcome for the displayed cluster. Same values are further plotted on the right in function of HR-TD subgroups (LOA and EOA). Results of comparisons between LOA/EOA and HR-TD and between HR-ASD and HR-TD are displayed on the same graph. *p<0.05. CWP: cluster-wise P-value; mCT: Mean cortical thickness between the two scan acquisitions; EOA: Early onset ASD; LOA: Late onset ASD
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