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.
Highlights
Frontostriatal circuitry plays an important role in social motivation, which is postulated to underlie deficits in social interaction and communication in Autism Spectrum Disorder (ASD) (Dawson et al, 2005, 2012; Chevallier et al, 2012)
The results of the present study indicated that increased connectivity between the orbitofrontal cortex (OFC) and nucleus accumbens (NAcc) was associated with fewer social and communicative deficits (SCD) deficits, suggesting that increased connectivity between these regions may function to reduce social difficulties among adolescents/young adults with high-functioning ASD
Future studies may wish to further examine potential hemispheric asymmetries in functional and structural connectivity in ASD. These results are in line with previous reports of increased functional connectivity between the striatum and frontal, temporal and parietal lobes as well as the pons in ASD (Turner et al, 2006; Di Martino et al, 2010)
Summary
Frontostriatal circuitry plays an important role in social motivation, which is postulated to underlie deficits in social interaction and communication in Autism Spectrum Disorder (ASD) (Dawson et al, 2005, 2012; Chevallier et al, 2012). Abnormalities in frontostriatal circuitry may underlie the two core deficits in ASD; social interaction and communication, and restricted interests and repetitive behaviors (Langen et al, 2011a,b; Chevallier et al, 2012; Dichter et al, 2012), as well as other cognitive and motor impairments that are associated with ASD. Frontostriatal circuits have a looped structure with cortical inputs feeding information to the striatum which in turn projects back to the cortex via the thalamus (Alexander et al, 1986, 1990). Primate studies have shown that frontostriatal projections are arranged into a number of parallel, integrative loops, with each loop comprising discrete regions of striatum, cortex, globus pallidus, substantia nigra and thalamus, and subserving specific motor, cognitive, or affective function (Groenewegen et al, 1999, 2003; Haber and Knutson, 2009). Information is primarily channelled from ventral limbic, to more dorsal cognitive and motor loops such that action decision-making is Frontiers in Human Neuroscience www.frontiersin.org
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