On the Spectrum

General introduction
functional neuroimaging is resting-state functional magnetic resonance imaging (RS-FMRI),
which relies on a phenomenon called intrinsic brain activity, or brain activity that is not
induced by an external stimulus. In the context of RS-FMRI, connectivity between different
brain regions is assessed through temporal fluctuations in the BOLD signal, where brain
regions with high temporal correlation are more connected. Studies of children with ASD have
repeatedly demonstrated abnormal patterns of functional connectivity, including both lower
connectivity than controls, (hypoconnectivity) and increased connectivity (hyperconnectivity)
(Uddin et al. 2013). However, the majority of existing resting-state functional MRI studies
have made the assumption that the brain’s functional connectivity is static over a period
of multiple minutes. This has been shown to be a major limitation as important dynamic
patterns of connectivity could be missed (Calhoun, Miller, Pearlson and Adali 2014). Recent
novel analysis methods provide the opportunity to study dynamic patterns of connectivity in
the context of ASD, as well as in typical development. These methods are used in chapter 5
to study whether children with ASD or traits of the disorder show different temporal patterns
of connectivity, in addition to differences in static connectivity.
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PART II: EMOTIONAL AND BEHAVIORAL PROBLEMS IN THE GENERAL
POPULATION
Classification of internalizing and externalizing problems
Two broad categories of child behavior are distinguished in developmental research:
internalizing and externalizing problems. Internalizing problems represent problems that
manifest mainly within the self, such as depressed mood or anxiety, while externalizing
problems are characterized by disruptive behaviors that are more likely to involve conflicts
with others (Achenbach and Rescorla 2000). Internalizing problems in childhood are very
predictive of later mood and anxiety disorders (Roza, Hofstra, van der Ende and Verhulst
2003), while externalizing problems often precede later diagnoses of ADHD or conduct
disorders (Moffitt 1993). Internalizing and externalizing problems can be quantified in
continuous dimensions using well-known questionnaires such as the Child Behavior Checklist
(CBCL) (Achenbach et al. 2000). Although internalizing and externalizing symptoms are
quite different in nature, they often co-occur: children that have a high level of externalizing
symptoms tend to also have internalizing symptoms (Achenbach et al. 2000). This phenotypic
overlap poses a challenge to the study of specific neurobiological or cognitive correlates.
Such specific correlates potentially contain crucial information. Firstly, it can help lead to
a better understanding of underlying mechanisms. Second, specific correlates can be of
importance in predicting the time course of psychopathology. Third, knowing the specific
relation of cognitive symptoms or biomarkers and specific psychiatric symptoms may be
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