The Limbic System in the Asperger Syndrome: a Preliminary Diffusion Tensor Tractography Study

Background: It has been suggested that people with Autistic Spectrum Disorder (ASD) have altered development (and connectivity) of limbic circuits^1,2.  However, direct evidence of anatomical differences specific to white matter pathways underlying social behavior and emotions in ASD, is lacking.

Objectives: We used Diffusion Tensor Imaging  (DTI) tractography to compare, in vivo, tract-specific measurements along the principal limbic pathways between people with Asperger syndrome and healthy controls.

Methods: We recruited 66 people: 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).  DTI were acquired on a 1.5 T GE Signa NV/i LX (General Electric, Milwaukee, WI) and processed as described by Jones at al³.  We quantified tract-specific diffusivity measurements as indirect indexes of tract volume (e.g. number of streamlines) and micro-structural organization and integrity (e.g. mean diffusivity, MD; and fractional anisotropy, FA) of the main limbic tracts.  These include the inferior longitudinal fasciculus (ILF), inferior frontal occipital fasciculus (IFOF), uncinate, cingulum and fornix.

Results: DTI measurements. Streamlines: People with Asperger syndrome had a significantly higher number of streamlines in the right (p=0.003) and left (p=0.03) cingulum and in the right (p=0.03) and left (p=0.04) inferior longitudinal fasciculus.  In contrast people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p=0.02).  The number of streamlines for the right (but not for the left) cingulum survived Bonferroni correction. Mean Diffusivity: The Asperger group showed significantly increase in the ILF bilaterally, and in the right cingulum and in the right IFOF.  Fractional anisotropy: individuals with Asperger syndrome had a significant decrease in FA within the IFOF bilaterally, and in the right uncinate fasciculus.  Age-related differences.  Streamlines: There were no significant age-related differences between groups.  Mean diffusivity: There was statistically significant age-related difference in mean diffusivity of the left uncinate fasciculus (Zobs=2.05) (p=0.02). Fractional Anisotropy: There were no age-related  between-group differences.

Conclusions: People with Asperger syndrome have significant differences in micro-structural integrity (and maturation) of some, but not all, limbic pathways. This may mostly affect (respectively) the cingulum and uncinate fasciculus. Our findings support previous reports of anatomical, metabolic and functional differences in the limbic regions of people with Asperger and may explain some of the social and emotional^4,5 anomalies typically found in the disorder. Further studies linking the involvement of these pathways are required.

References: 1) Courchesne E,et al. Curr. Opin. in Neurobiology. 2005;15(2):225-230. 2) Jones D. Hum.Brain Mapp. 2002;15(4):216-30 3)  Wickelgren I. Science. 2005;308(5730):1856-8. 4) Damasio AR. Arch Neurol. 1978;35(12):777-86. 5) Mundy P. J Child Psychol Psych. 2003;44(6):793-809.