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Insistence on sameness relates to increased covariance of gray matter structure in autism spectrum disorder.

Eisenberg IW, Wallace GL, Kenworthy L, Gotts SJ, Martin A - Mol Autism (2015)

Bottom Line: Subcortical structural changes have been associated with restricted and repetitive behavior (RRB), a core component of ASD.We found that increased coupling among subcortical regions and between subcortical and cortical regions related to greater IS symptom severity.These structural associations were specific to IS and did not relate to any of the other RRB subcomponents measured by the RBS-R.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD USA.

ABSTRACT

Background: Autism spectrum disorder (ASD) is characterized by atypical development of cortical and subcortical gray matter volume. Subcortical structural changes have been associated with restricted and repetitive behavior (RRB), a core component of ASD. Behavioral studies have identified insistence on sameness (IS) as a separable RRB dimension prominent in high-functioning ASD, though no simple brain-behavior relationship has emerged. Structural covariance, a measure of morphological coupling among brain regions using magnetic resonance imaging (MRI), has proven an informative measure of anatomical relationships in typical development and neurodevelopmental disorders. In this study, we use this measure to characterize the relationship between brain structure and IS.

Methods: We quantified the structural covariance of cortical and subcortical gray matter volume in 55 individuals with high-functioning ASD using 3T MRI. We then related these structural metrics to individual IS scores, as assessed by the Repetitive Behavior Scale-Revised (RBS-R).

Results: We found that increased coupling among subcortical regions and between subcortical and cortical regions related to greater IS symptom severity. Most pronounced, the striatum and amygdala participated in a plurality of identified relationships, indicating a central role for these structures in IS symptomatology. These structural associations were specific to IS and did not relate to any of the other RRB subcomponents measured by the RBS-R.

Conclusions: This study indicates that behavioral dimensions in ASD can relate to the coordination of development across multiple brain regions, which might be otherwise obscured using typical brain-behavior correlations. It also expands the structures traditionally related to RRB in ASD and provides neuroanatomical evidence supportive of IS as a separate RRB dimension.

Trial registration: ClinicalTrials.gov NCT01031407.

No MeSH data available.


Related in: MedlinePlus

Intra-subcortical correlational analysis. Intra-subcortical correlational analysis showing the relationship between IS severity and Region X Region structural covariance, as measured by a single-subject covariance analog (see “Statistical analysis” section). FDR cutoff indicated by **. Relationships that survive FDR correction are displayed in the lower triangle. See Additional file 6: Table S1 for exact r and p values for significant relationships
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Fig2: Intra-subcortical correlational analysis. Intra-subcortical correlational analysis showing the relationship between IS severity and Region X Region structural covariance, as measured by a single-subject covariance analog (see “Statistical analysis” section). FDR cutoff indicated by **. Relationships that survive FDR correction are displayed in the lower triangle. See Additional file 6: Table S1 for exact r and p values for significant relationships

Mentions: The correlational analysis produced more robust results that were qualitatively consistent with the group comparisons described above (Fig. 2). In the subcortex, every Region X Region relationship was positively correlated with IS symptomatology (Spearman r = .29 ± .12), with six surviving correction for multiple comparisons (p < .0052 for all; FDR, q < .05; shown in the lower triangle in Fig. 2 with labels shown in Fig. 1; see Additional file 6: Table S1 for a complete list of region pairs that survived correction and Additional file 7: Figure S5 for example scatter plots of the relationship between IS and Region X Region association strength). Most of the subcortex was implicated in this analysis including the putamen, amygdala, hippocampus, pallidum, and accumbens.Fig. 2


Insistence on sameness relates to increased covariance of gray matter structure in autism spectrum disorder.

Eisenberg IW, Wallace GL, Kenworthy L, Gotts SJ, Martin A - Mol Autism (2015)

Intra-subcortical correlational analysis. Intra-subcortical correlational analysis showing the relationship between IS severity and Region X Region structural covariance, as measured by a single-subject covariance analog (see “Statistical analysis” section). FDR cutoff indicated by **. Relationships that survive FDR correction are displayed in the lower triangle. See Additional file 6: Table S1 for exact r and p values for significant relationships
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591718&req=5

Fig2: Intra-subcortical correlational analysis. Intra-subcortical correlational analysis showing the relationship between IS severity and Region X Region structural covariance, as measured by a single-subject covariance analog (see “Statistical analysis” section). FDR cutoff indicated by **. Relationships that survive FDR correction are displayed in the lower triangle. See Additional file 6: Table S1 for exact r and p values for significant relationships
Mentions: The correlational analysis produced more robust results that were qualitatively consistent with the group comparisons described above (Fig. 2). In the subcortex, every Region X Region relationship was positively correlated with IS symptomatology (Spearman r = .29 ± .12), with six surviving correction for multiple comparisons (p < .0052 for all; FDR, q < .05; shown in the lower triangle in Fig. 2 with labels shown in Fig. 1; see Additional file 6: Table S1 for a complete list of region pairs that survived correction and Additional file 7: Figure S5 for example scatter plots of the relationship between IS and Region X Region association strength). Most of the subcortex was implicated in this analysis including the putamen, amygdala, hippocampus, pallidum, and accumbens.Fig. 2

Bottom Line: Subcortical structural changes have been associated with restricted and repetitive behavior (RRB), a core component of ASD.We found that increased coupling among subcortical regions and between subcortical and cortical regions related to greater IS symptom severity.These structural associations were specific to IS and did not relate to any of the other RRB subcomponents measured by the RBS-R.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD USA.

ABSTRACT

Background: Autism spectrum disorder (ASD) is characterized by atypical development of cortical and subcortical gray matter volume. Subcortical structural changes have been associated with restricted and repetitive behavior (RRB), a core component of ASD. Behavioral studies have identified insistence on sameness (IS) as a separable RRB dimension prominent in high-functioning ASD, though no simple brain-behavior relationship has emerged. Structural covariance, a measure of morphological coupling among brain regions using magnetic resonance imaging (MRI), has proven an informative measure of anatomical relationships in typical development and neurodevelopmental disorders. In this study, we use this measure to characterize the relationship between brain structure and IS.

Methods: We quantified the structural covariance of cortical and subcortical gray matter volume in 55 individuals with high-functioning ASD using 3T MRI. We then related these structural metrics to individual IS scores, as assessed by the Repetitive Behavior Scale-Revised (RBS-R).

Results: We found that increased coupling among subcortical regions and between subcortical and cortical regions related to greater IS symptom severity. Most pronounced, the striatum and amygdala participated in a plurality of identified relationships, indicating a central role for these structures in IS symptomatology. These structural associations were specific to IS and did not relate to any of the other RRB subcomponents measured by the RBS-R.

Conclusions: This study indicates that behavioral dimensions in ASD can relate to the coordination of development across multiple brain regions, which might be otherwise obscured using typical brain-behavior correlations. It also expands the structures traditionally related to RRB in ASD and provides neuroanatomical evidence supportive of IS as a separate RRB dimension.

Trial registration: ClinicalTrials.gov NCT01031407.

No MeSH data available.


Related in: MedlinePlus