Functional and Structural Connectivity of Frontostriatal Circuitry in ASD

Background:  

Frontostriatal circuitry subserves goal-directed action, playing a key role in emotion, motivation, cognition and the control of movement. Abnormal function and/or connectivity of this circuit may underlie deficits in social interaction and communication, restricted interests and repetitive behaviours and/or other cognitive deficits in ASD. However, few studies have examined connectivity within this circuit in ASD and no previous study has examined both functional and structural connectivity within the same population.

 Objectives:  

To examine frontostriatal functional connectivity in ASD and to use diffusion tensor imaging (DTI) to investigate associated differences in structural connectivity.

 Methods:

28 right-handed male participants with high functioning ASD and 27 right-handed male, age and IQ matched controls took part in the MRI study (Mean age: ASD=17.28 (SD= 3.57); Control=17.15 (SD= 3.64); Mean IQ ASD= 109.25 (SD= 15.04); Control=111.85 (SD= 12.32)). 21 ASD and control participants were retained for the fMRI analysis and 22 ASD and 24 control participants were included in the DTI analysis after excluding subjects for factors such as excessive motion (movements >3mm) and poor data quality. fMRI preprocessing was carried out in SPM8 and functional connectivity analysis was carried out using the CONN toolbox. Seed regions for the functional connectivity analysis were defined within the left and right frontal cortex. Target regions included the left and right striatum (caudate, putamen, accumbens). All ROIs were generated using the Harvard-Oxford probabilistic atlas. DTI preprocessing and analysis was carried out using Explore DTI. Tractography analysis was carried out between the frontal cortex and striatal regions that showed significant differences in functional connectivity, and was confined to intra-hemispheric tracts (i.e. right frontal cortex to right accumbens and right caudate). Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD) were extracted for each tract of interest. T-tests and Mann-Mann-Whitney tests were carried out to examine group differences in functional and structural connectivity respectively. Results were corrected for multiple comparisons using an FDR correction (p<.05).

Results:

The ASD group showed increased functional connectivity between the right anterior cingulate and right accumbens/left caudate, the right middle frontal gyrus and right accumbens/right caudate, the right paracingulate gyrus and right accumbens /right caudate and the left paracingulate gyrus and the right accumbens/right caudate. There were no regions that showed significantly reduced connectivity between the frontal cortex and the striatum. Although tracts were reliably constructed for each subject there were no group differences in structural connectivity (FA, MD, RD, AD) in the tracts of interest.

 Conclusions:  

Results are in keeping with previously reported increased corticostriatal functional connectivity among children with ASD and indicate that increased frontostriatal connectivity persists among adolescents and young adults with ASD. Increased connectivity was recorded in cognitive and limbic (but not sensorimotor circuits) suggesting that abnormal frontostriatal connectivity may be implicated in social and cognitive deficits in ASD. There were no differences in structural connectivity as measured by DTI, suggesting that functional connectivity measures may be more sensitive to differences in connectivity among older subjects with high functioning ASD.