On the Spectrum
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Chapter 8<br />
gyrification changes in postnatal life as well (White, Su, Schmidt, Kao and Sapiro 2010). In this<br />
<strong>the</strong>sis, we found widespread reductions in gyrification to be associated with autistic traits<br />
and we found a trend toward <strong>the</strong> same effect in a small subset of children that met criteria<br />
for ASD according to <strong>the</strong> golden standard instruments. This association held in a subset of<br />
regions when we excluded <strong>the</strong> most severely affected children, indicating a true continuum<br />
in <strong>the</strong> neurobiology. Our finding of reduced gyrification is in line with some studies of young<br />
children with ASD (Schaer, Ottet, Scariati, Dukes, Franchini et al. 2013; Bos, Merchan-Naranjo,<br />
Martinez, Pina-Camacho, Balsa et al. 2015). However, <strong>the</strong>re have also been studies that found<br />
<strong>the</strong> opposite (Kates, Ikuta and Burnette 2009; Wallace, Robustelli, Dankner, Kenworthy, Giedd<br />
et al. 2013). This discrepancy can partly be understood from differences in methodology, as<br />
well as gender, age and IQ of <strong>the</strong> study sample. However, a recent clinical study in children of<br />
a similar age range, using <strong>the</strong> same methodology reported <strong>the</strong> opposite finding in children<br />
with ASD (Yang, Beam, Pelphrey, Abdullahi and Jou 2016). Considering this heterogeneity, we<br />
cannot be sure of <strong>the</strong> nature of gyrification differences in young children with ASD.<br />
<strong>On</strong>e of <strong>the</strong> <strong>the</strong>ories of gyrification suggests that it reflects connection strength between<br />
spatially separated regions of <strong>the</strong> brain (Van Essen 1997), and two previous studies that<br />
combined gyrification and white matter measurements revealed white matter disruptions<br />
alongside reduced gyrification in children with ASD (Schaer et al. 2013; Bos et al. 2015).<br />
Based on our previous findings of reduced gyrification, we hypo<strong>the</strong>sized a continuum in<br />
white matter microstructure related to autistic traits, so that white matter differences related<br />
to autistic traits would mimic those most commonly reported in children with ASD. Studies<br />
of children with ASD show alterations in white matter microstructure, most notably in tracts<br />
that facilitate long-range connections: corpus callosum, <strong>the</strong> left uncinated fasciculus, and <strong>the</strong><br />
left superior longitudinal fasciculus (Aoki, Abe, Nippashi and Yamasue 2013). We detected<br />
a localized association between autistic traits and lower white matter integrity in a small<br />
region in <strong>the</strong> superior longitudinal fasciculus. In this long-range white matter tract, we<br />
found a continuous association with autistic traits, that remained after excluding children<br />
with ASD. However, we did not find major differences in all of <strong>the</strong> hypo<strong>the</strong>sized long-range<br />
white matter connections in <strong>the</strong>se children. White matter integrity in some of <strong>the</strong>se tracts<br />
may not relate to this quantitative measure of social impairment, thus disruptions may occur<br />
more exclusively at <strong>the</strong> severe end of <strong>the</strong> spectrum. Alternatively, associations may only be<br />
revealed in samples where children generally have more severe symptoms.<br />
Our findings in functional connectivity offer more support for <strong>the</strong> conceptualization of<br />
ASD as a ‘disconnection syndrome’, where symptoms are thought to arise from disturbances<br />
in neural circuitry (Geschwind and Levitt 2007). Using a novel type of resting state fMRI<br />
analysis, where assumptions of stationarity of functional connectivity over time were<br />
relaxed, we found that children with more autistic traits showed alterations in <strong>the</strong>se dynamic<br />
connectivity characteristics. Specifically, <strong>the</strong>y spent less time in <strong>the</strong> more heavily connected,<br />
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