Functional and structural connectivity of frontostriatal circuitry in Autism Spectrum Disorder

Abstract

Abnormalities in frontostriatal circuitry potentially underlie the two core deficits in Autism Spectrum Disorder (ASD); social interaction and communication difficulties and restricted interests and repetitive behaviors. Whilst a few studies have examined connectivity within this circuitry in ASD, no previous study has examined both functional and structural connectivity within the same population. The present study provides the first exploration of both functional and structural frontostriatal connectivity in ASD. Twenty-eight right-handed Caucasian male ASD (17.28 ± 3.57 years) and 27 right-handed male, age and IQ matched controls (17.15 ± 3.64 years) took part in the study. Resting state functional connectivity was carried out on 21 ASD and control participants, and tractography was carried out on 22 ASD and 24 control participants, after excluding subjects for excessive motion and poor data quality. Functional connectivity analysis was carried out between the frontal cortex and striatum after which tractography was performed between regions that showed significant group differences in functional connectivity. The ASD group showed increased functional connectivity between regions in the frontal cortex [anterior cingulate cortex (ACC), middle frontal gyrus (MFG), paracingulate gyrus (Pcg) and orbitofrontal cortex (OFC)], and striatum [nucleus accumbens (NAcc) and caudate]. Increased functional connectivity between ACC and caudate was associated with deactivation to social rewards in the caudate, as previously reported in the same participants. Greater connectivity between the right MFG and caudate was associated with higher restricted interests and repetitive behaviors and connectivity between the bilateral Pcg and NAcc, and the right OFC and NAcc, was negatively associated with social and communicative deficits. Although tracts were reliably constructed for each subject, there were no group differences in structural connectivity. Results are in keeping with previously reported increased corticostriatal functional connectivity in ASD.

Keywords: Autism Spectrum Disorder; DTI; connectivity; fMRI; frontostriatal; social reward; striatum.

Figure 1

Scatterplot showing individual mean framewise displacement. Individual subjects are shown on the x-axis and framewise displacement (mm) on the y-axis. ASD subjects are shown as gray diamonds and controls as white squares. The dashed vertical line divides the two groups. Solid horizontal lines across the ASD and Control values show the group mean.

Figure 2

Masks for the frontal cortex (only the left hemisphere is shown). ACC is shown in red, the OFC in blue, the MPFC in green, frontal pole in violet, IFG opercularis in yellow, IFG triangularis in cyan, juxapositional lobe in green, MFG in yellow, paracingulate in blue, precentral gyrus in light blue, SFG in grayscale and the subcallosal gyrus in yellow, displayed on the left hemisphere of a standard brain in neurological convention (left is left and right is right).

Figure 3

Masks for the striatum and amygdala. The NAcc is shown in yellow, the caudate in green, the putamen in red and the amydgala in blue displayed on the right hemisphere of a standard brain in neurological convention (left is left).

Figure 4

Caudate and NAcc tracts for the template subject. Tracts are shown in the axial (left) and sagittal (right) planes in neurological convention (left is left). The caudate-prefrontal tracts are shown in yellow and NAcc-prefrontal tracts are shown in red.

Figure 5

Group differences in functional connectivity between the frontal cortex and the striatum. Bar charts show Z-transformed R-Values for connectivity between each of the regions for which there was a significant group difference, adjusting for age, IQ and frame-wise displacements. The ASD group is shown in gray and the controls in white with standard error of the mean displayed. R, Right; L, Left; ACC, Anterior Cingulate Cortex; MFG, Middle Frontal Gyrus; Pcg, Paracingulate Gyrus; NAcc, Nucleus Accumbens; Caud, Caudate.

Figure 6

Connectivity between the left caudate and right anterior cingulate and activation to social rewards in the left caudate. Connectivity values are shown on the x-axis and percent signal change for social reward feedback is shown on the y-axis. The ASD group is shown in gray (with dashed trend-line) and the controls in white (with solid black trend-line).

Figure 7

Plots of the correlations between connectivity values and behavioral measures for the ASD group. Connectivity values are shown on the x-axes and scores on the behavioral measures on the y-axes. ASD single subjects are represented as gray diamonds (solid black trend-line).