Reduced Connectivity is confined to Amygdala Input and not Output Areas in Functional ASD Networks during Rest
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2014-01-28
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en
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Autism is a behaviorally defined disorder with limited social skills, communicative difficulties, reduced attention switching, restricted interests and repetitive stereotyped behavior as well as limited imagination and mentalizing. Not only people with autism experience difficulties in daily life, their families often suffer a financial and psychological burden as well (Bägenholm and Gillberg 1991, Roeyers and Mycke 1995). Despite its burden and high prevalence (1 percent of the general population) (Kim, Leventhal et al. 2011 ), little is known about the causes and underlying pathophysiological mechanisms of autism spectrum disorders (ASD). Yet, a basic understanding of ASD as a disorder of the brain is needed to develop effective biological treatments.
Prior research revealed white and grey matter abnormalities in the limbic system including cingulate cortex, hippocampus, amygdala (Schumann, Hamstra et al. 2004, Groen, Teluij et al. 2010), thalamus (Hardan, Girgis et al. 2006) and cortical areas such as frontal lobe (Damasio and Maurer 1978, MunDy 2013), superior temporal area (Boddaert, Chabane et al. 2004) and sensorimotor cortex (Perry, Minassian et al. 2007). Many of these structures have been linked to specific autistic behaviors during task based neuroimaging experiments (for a review see Amaral, Schumann et al. (2008). Especially abnormalities in structures comprising emotion regulating circuits were found affected in autism, with the amygdala as a key component in ASD (Baron-Cohen, Ring et al. 2000).
The amygdala is situated within the temporal lobe. It is associated with social cognition, emotion recognition, emotional valence and regulation of personal space in the context of anxiety and fear invoking stimuli (Phelps and LeDoux 2005). Still, structural and functional studies investigating the amygdala in ASD have yielded inconclusive results. One reason for the mixed results may be the fact that the amygdala is usually treated as a single structure, while in fact it is comprised of at least 13 functionally and structurally distinct nuclei that can be classified into three main amygdalar subdivisions: the superfiscial, centromedial and laterobasal group. The centromedial part (CM) is the output area, which regulates cardiovacular control via projections to brainstem, cerebellum and hypothalamus (Davis, 1997; LeDoux, 2003). The laterobasal nucleus (LB) is linked to multisensory input and facilitates emotional learning (LeDoux, 2003; Phelps and LeDoux, 2005), whereas the superficial compartments (SF) maintain olfactory and striatal (Price 2003, Heimer and Van Hoesen 2006) projections. LB and SF are therefore mainly identified with amygdala input functionality. Functional neuroimaging studies confirm these distinctions in the human amygdala (Ball, Rahm et al. 2007, Bickart, Wright et al. 2010).
With last decade's paradigm shift in neuro-imaging from activity assessment within isolated structures to connectivity within large-scale networks, researchers have increasingly found evidence for abnormal neural connectivity in ASD. The term connectivity refers to the degree of synchrony of neural firing pattems, usually assessed with resting state fMRI. Some authors (Courchesne and Pierce 2005) hypothesized that the brain in ASD is characterized by long distance underconnectivity and local overconnectivity in autism. Others (Happé 1999, Wass).
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Faculteit der Sociale Wetenschappen