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Abstract
 
Abstract
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It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23 ± 12 years, age range: 9–54 years) and 42 age-matched male controls (mean age 25 ± 10 years, age range: 9–54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p  = .003) and left (p  = .03) cingulum, and in the right (p  = .03) and left (p  = .04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p  = .02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Zobs = 2.05) (p  = .02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.
 
It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23 ± 12 years, age range: 9–54 years) and 42 age-matched male controls (mean age 25 ± 10 years, age range: 9–54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p  = .003) and left (p  = .03) cingulum, and in the right (p  = .03) and left (p  = .04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p  = .02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Zobs = 2.05) (p  = .02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.
Keywords
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 +
* Keywords
 
Asperger; Limbic system; White matter; Diffusion tensor; Tractography
 
Asperger; Limbic system; White matter; Diffusion tensor; Tractography
Input Author
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* Input Author
 
Luca Pugliese
 
Luca Pugliese
[edit]MANUSCRIPT DETAILS
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 +
MANUSCRIPT DETAILS
 
Introduction/Aims
 
Introduction/Aims
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ASD (which includes Asperger’s and autism) is a neurodevelopmental disorder characterized by impaired communication, difficulty in social interaction, and repetitive and stereotypic behavior (WHO, 1993).
 
ASD (which includes Asperger’s and autism) is a neurodevelopmental disorder characterized by impaired communication, difficulty in social interaction, and repetitive and stereotypic behavior (WHO, 1993).
 
The limbic system in humans is involved in emotion regulation, attention processing, and decision making, and social behavior.  Structures such as the cingulate, orbitofrontal cortex, hippocampus, and amygdale all regulate functions that ASD patients have deficits in.   
 
The limbic system in humans is involved in emotion regulation, attention processing, and decision making, and social behavior.  Structures such as the cingulate, orbitofrontal cortex, hippocampus, and amygdale all regulate functions that ASD patients have deficits in.   

Revision as of 00:57, 10 February 2010

MANUSCRIPT ID

  • Title
  • Reference
  • Abstract
  • Keywords
  • Input Author


MANUSCRIPT DETAILS

  • Introduction/Aims
  • Methods
  • Results
  • Summary
  • Discussion


MANUSCRIPT ID

The anatomy of extended limbic pathways in Asperger syndrome: A preliminary diffusion tensor imaging tractography study

  • Reference

NeuroImage Volume 47, Issue 2, 15 August 2009, Pages 427-434


Abstract

It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23 ± 12 years, age range: 9–54 years) and 42 age-matched male controls (mean age 25 ± 10 years, age range: 9–54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p = .003) and left (p = .03) cingulum, and in the right (p = .03) and left (p = .04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p = .02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Zobs = 2.05) (p = .02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.

  • Keywords

Asperger; Limbic system; White matter; Diffusion tensor; Tractography

  • Input Author

Luca Pugliese

MANUSCRIPT DETAILS Introduction/Aims

ASD (which includes Asperger’s and autism) is a neurodevelopmental disorder characterized by impaired communication, difficulty in social interaction, and repetitive and stereotypic behavior (WHO, 1993). The limbic system in humans is involved in emotion regulation, attention processing, and decision making, and social behavior. Structures such as the cingulate, orbitofrontal cortex, hippocampus, and amygdale all regulate functions that ASD patients have deficits in. It has been suggested that some of the social and communication abnormalities typically found in people with ASD are secondary (Damasio and Maurer, 1978) to abnormalities in limbic structures, and perhaps also in their connectivity ([Courchesne and Pierce, 2005b]and [Wickelgren, 2005]). This study uses Diffusion Tensor Imaging and tractography to see if there are any differences in the connections in white matter tracts in the limbic system between healthy controls and Asperger’s patients. Methods Participants included 24 males with Asperger’s syndrome and 42 healthy controls. MRI images were acquired by multislice echo planar imaging. Whole brain volumetric measurements were acquired using Measure software.

Diffusion tensors were calculated for each voxel. From these Fractional Anisotropy (FA) maps were created which quantifies the directionality of the diffusion. Seed regions were chosen, and tracts were reconstructed by following the principle eigenvectors at each voxel. At areas where the tracts branch, new seed regions were defined at the branch so that both branches could be visualized. Number and length of streamlines (SL) were calculated for each tract. Also fractional anisotropy (FA) and mean diffusivity (MD) at regular (.5 mm) intervals along the defined tracts were extracted and the means for each tract computed

Results No significant difference in age, though there was a significant difference in IQ. No statistical differences in whole brain volumes. FA and MD values were significantly different between healthy controls and Asperger’s patients in the ILF, IFOF, and cingulated, but not after Bonferroni correction (see fig. 1 and 2). The Asperger’s group showed higher numbers of streamlines, especially in the inferior longitudinal fasciculus and the cingulum (see Fig.3 ). Also, the Asperger’s group showed age-related differences in that their streamlines did not increase over time, whereas healthy controls did( see fig.4). Summary Significant differences in streamlines in inferior longitudinal fasciculus and esp. right cingulum. There do appear to be differences in microstructure and directionality of the white matter tracts in the limbic system in Asperger’s syndrome; however, these are not significant after Bonferroni correction. The Asperger’s group appear to have a higher number of streamlines but experience no growth of tracts later. Higher leptin levels were also associated with larger brain parenchymal volume, and smaller ventricular volume.


Discussion Significant differences in streamlines in inferior longitudinal fasciculus and esp. right cingulum could reflect different methods of processing of empathy and social cognition. Previous studies have showed decreased glucose metabolism in these areas; this study shows there are structural differences as well. Anterior and posterior cortices form the “default network”, which activates when people are at rest or thinking about the future. Differences in structure in these areas could explain some of the more internal driven self-reflective thinking of ASD. FA and MD measurements, though not significant, showed higher MD and lower FA in Asperger’s patients, which suggest structural damage to axon membranes, leading to higher diffusivity and lower anisotropy.