Laterobasal Amygdalar Enlargement in 6- to 7-Year-Old Children With Autism Spectrum Disorder

Department of Psychiatry, Seoul National University, Seoul, South Korea.
Archives of general psychiatry (Impact Factor: 14.48). 11/2010; 67(11):1187-97. DOI: 10.1001/archgenpsychiatry.2010.148
Source: PubMed


There is substantial imaging evidence for volumetric abnormalities of the amygdala in younger children with autism spectrum disorder (ASD). The amygdala can be divided into functionally distinct laterobasal, superficial, and centromedial subregions. To date, we are not aware of any in vivo reports specifically assessing subregional amygdalar abnormalities in individuals with ASD.
To evaluate alterations in subregional amygdalar morphology in children with ASD compared with typically developing (TD) children and to examine the relationships with ASD symptom severity.
A cross-sectional study encompassing a narrow age range of children with ASD and age-matched TD children that evaluated magnetic resonance imaging-defined subregional morphology of the amygdala using a novel subregional analytic method.
Participants were recruited and clinically evaluated through the University of Washington Autism Center and imaged at the Diagnostic Imaging Sciences Center at the University of Washington. Imaging data were analyzed through the Brain Imaging Laboratory at the Seoul National University.
Fifty-one children 6 to 7 years of age (ASD, n = 31 and TD, n = 20) were assessed using magnetic resonance imaging and behavioral measures.
Volume and subregional measures of the amygdala and measures of social and communication functioning.
The ASD group exhibited larger right and left amygdalae, by 12.7% and 11.0%, respectively, relative to the TD group. Subregional analysis revealed that the ASD group had enlarged laterobasal amygdalar subregions, relative to the TD group, after adjusting for age, sex, and hemispheric cerebral volume (P < .05, false discovery rate corrected and with clustered surface points >15). Exploratory analyses revealed that there were linear trends comparing a strictly defined subgroup of children with autistic disorder, who exhibited the greatest extent of laterobasal enlargement, followed by a subgroup of children with pervasive developmental disorder not otherwise specified and then the group of TD children (P for linear trend <.001). There were linear trends between enlargement of laterobasal subregions and lower levels of social and communication functioning (P < .001, P < .001, and P = .001 for 3 areas in the right laterobasal subregion; P < .001 for 1 area in the left laterobasal subregion).
The current study demonstrates bilateral enlargement of laterobasal subregions of the amygdala in 6- to 7-year-old children with ASD and that subregional alterations are associated with deficits in social and communicative behavior.

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    • "Using cytoarchitechtonic probabilistic maps of amygdala subnuclei provided in FSL's Juelich histological atlas [Amunts et al., 2005], BLA and CMA region of interest (ROI) masks were created in both hemispheres (see Supporting Information 1). These probability maps have been validated in pediatric postmortem studies [Kim et al., 2010], and have proven highly reliable and accurate in guiding amygdala parcellation in pediatric populations [Gabard-Durnam et al., 2014; Qin et al., 2012, 2014; Roy et al., 2013]. In line with recent developmental studies [Qin et al., 2012, 2014], voxels were included in the ROI masks only if the probability of their assignment to the BLA or CMA was higher than any other nearby structures with greater than 40% likelihood. "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets. Hum Brain Mapp, 2016.
    Full-text · Article · Jan 2016 · Human Brain Mapping
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    • "The amygdala is supposed to play a central role in the etiopathology of ASDs and several theoretical explanations compatible with the amygdala dysfunction have been proposed to account for socio-emotional impairments, including abnormal eye contact, poor recognition of fear and other negative emotions, face processing, mental state understanding and empathy (Baron-Cohen et al., 2000; Amaral, Bauman & Schumann, 2003; Ashwin et al., 2006; Kim et al., 2010; Kliemann et al., 2012). As posit by the " Relevance Detection Theory " (Sander, Grafman & Zalla, 2003), the human amygdala is a component of this extended neural cortico-limbic system involved in detecting stimuli by focusing attentional and physiological resources on cues that have special relevance for the safety or success of an organism within the broader context of its social life. "
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    ABSTRACT: Impairments in emotional processing in Autism Spectrum Disorders (ASDs) can be characterised by failure to generate and recognize self-reflective, cognitive-based emotions, such as pride, embarrassment and shame. Among this type of emotions, regret and disappointment, as well as their positive counterparts, result from a counterfactual comparison, that is the comparison between an actual value (“what is”) and a fictive value (“what might have been”). However, while disappointment is experienced when the obtained outcome is worse than the expected outcome that might have occurred from the same choice, regret occurs when one experiences an outcome that is worse than the outcome of foregone choices. By manipulating a simple gambling task, we examined subjective reports on the intensity of negative and positive emotions in a group of adults with High Functioning Autism or Asperger syndrome (HFA/AS), and a control group matched for age, gender and educational level. Participants were asked to choose between two lotteries with different levels of risk under two conditions of outcome feedback: (i) Partial, in which only the outcome of the chosen lottery was visible, (ii) Complete, in which the outcomes of the two lotteries were simultaneously visible. By comparing partial and complete conditions, we aimed to investigate the differential effect between disappointment and regret, as well as between their positive counterparts. Relative to the control participants, the group with HFA/AS reported reduced regret and no difference between regret and disappointment, along with a preserved ability to use counterfactual thinking and similar choice behavior. Difficulties to distinguish the feeling of regret in participants with HFA/AS can be explained by diminished emotional awareness, likely associated with an abnormal fronto-limbic connectivity.
    Full-text · Article · Sep 2014 · Cortex
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    • "In adult and animal studies both the BLA and CMA play a pivotal role in numerous emotion-related functions. Specifically, the CMA is thought to be critical for controlling the expression of fear (Qin et al., 2012) whereas the BLA is thought to play a critical role in perception , appraisal, and regulation of emotionally salient stimuli (Kim et al., 2010a). Thus, we hypothesized that activity in both the BLA and CMA would be modulated by CER. "
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    ABSTRACT: When used effectively, cognitive reappraisal of distressing events is a highly adaptive cognitive emotion regulation (CER) strategy, with impairments in cognitive reappraisal associated with greater risk for psychopathology. Despite extensive literature examining the neural correlates of cognitive reappraisal in healthy and psychiatrically ill adults, there is a dearth of data to inform the neural bases of CER in children, a key gap in the literature necessary to map the developmental trajectory of cognitive reappraisal. In this fMRI study, psychiatrically healthy schoolchildren were instructed to use cognitive reappraisal to modulate their emotional reactions and responses of negative affect after viewing sad photos. Consistent with the adult literature, when actively engaged in reappraisal compared to passively viewing sad photos, children showed increased activation in the vlPFC, dlPFC, and dmPFC as well as in parietal and temporal lobe regions. When children used cognitive reappraisal to minimize their experience of negative affect after viewing sad stimuli they exhibited dampened amygdala responses. Results are discussed in relation to the importance of identifying and characterizing neural processes underlying adaptive CER strategies in typically developing children in order to understand how these systems go awry and relate to the risk and occurrence of affective disorders.
    Full-text · Article · Feb 2014
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