A single link to the first track to allow the export script to build the search page
  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    809—Brain Imaging and Tissue Markers in Autism

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    809.09: Abnormal connectivity in amygdala subregions in ASD: A resting state fMRI study

    Location: Halls B-H

    *N. M. KLEINHANS1, G. PAULEY1, E. NEUHAUS2, N. MARTIN1;
    1Dept Radiology, 2Dept of Psychiatry, Univ. Washington, SEATTLE, WA

    Abstract Body: The amygdala is a complex structure with distinct subregions and dissociable functional networks. It has been hypothesized that the lateral nucleus of the amygdala primarily drives the presentation and severity of autism symptoms, although very little data is available regarding amygdala dysfunction at the subregional level. In this study, we investigated the relationship between abnormal amygdalar intrinsic connectivity, autism symptom severity, and anxiety and depressive symptoms. We collected resting state fMRI data on 24 high functioning adults with an autism spectrum disorder and 32 typically developing (TD) controls aged 18-45. Eighteen participants with ASD and 22 TD participants were included in the final analyses. ASD participants were administered the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). All participants were administered the Beck Depression Inventory II and the Beck Anxiety Inventory. Functional connectivity analyses were conducted from three cytoarchitectonically determined amygdala subregions: centromedial (CM), laterobasal (LB) and superficial (SF). The ASD group showed significantly decreased connectivity from the LB subregion and increased connectivity from the CM and SF subregions compared to typically developing controls. Higher scores on the ADI-R were specifically associated with reduced connectivity from the left LB subregion. Higher ADOS social scores were associated with increase connectivity from the right CM and right SF subregions and decreased connectivity from the left LB subregions. Mood symptoms in the ASD participants were associated with both increased and decreased connectivity from the LB and SF subregions, in brain regions that were distinct from the correlations with core autism symptoms. Our findings provide new evidence of subregional differences in amygdala pathophysiology in ASD. Notably, in ASD, we find evidence of underconnectivity from the LB subregion and overconnectivity from the CM and SF subregions. These differences do not appear to be driven by co-morbid depression and anxiety.

    Lay Language Summary: Functional connections between subregions of the amygdala and other parts of the brain are both abnormally weaker and abnormally stronger in autism spectrum disorders. Weaker connections were observed from the laterobasal subregion, a group of nuclei that are involved in social behavior and emotion. Stronger than normal connections were observed from the centromedial and superficial subregions, which are involved emotional arousal and olfaction. The strength of connectivity between brain regions was related to how severe the participants’ autism symptoms were and their self-reported ratings of anxiety and depression. One of the challenges of studying autism in older individuals is the frequent occurrence of co-morbid anxiety and depression. Notably, the brain connections that were related to symptoms of autism were different than the ones related to mood disorder, suggesting that these conditions may involve different brain circuits.
    The amygdala is a small, almond-shaped structure located deep within the brain. It has many connections and is involved in multiple functions. This study provides the first evidence that the connections between the amygdala and other brain regions are not uniformly dysfunctional in autism, suggesting that there may be subregional differences in the mechanisms that give rise to autism symptoms. Thus, the widely used approach to studying the amygdala in autism, by averaging across the whole structure, likely obscured all but the most severe defects and potentially contributed to inconsistent reports across scientific papers. Further, these findings challenge the hypothesis that psychiatric symptoms, not social impairment per se, contribute to aberrant amygdala function in autism. This theory is based on the fact that the amygdala appears to be involved in almost every psychiatric disorder. Although the amygdala’s importance in social behaviors is well-documented, no previous study has looked at both mood disorders and autism symptoms within the same participants.
    We collected resting state functional magnetic resonance imaging (fMRI) data on 24 high functioning adults with an autism spectrum disorder and 32 typically developing controls aged 18-45. Participants were told to simply close their eyes, lay still, stay awake, and let their mind wander. Brain signals were extracted from three amygdala subregions: centromedial, laterobasal, and superficial. We then tested how well synchronized the signals from the amygdala subregions were to the signals from other parts of the brain. The strength of the connections were statistically compared between the groups and correlated to our behavioral measures. In addition to the fMRI scan, autism participants were administered the Autism Diagnostic Interview - Revised and the Autism Diagnostic Observation Schedule. The autism severity ratings were based on these measures. All participants responded to the questions on the Beck Depression Inventory II and the Beck Anxiety Inventory.
    Compared to the control group, the individuals with autism showed weaker connectivity between the laterobasal amygdala and brain regions involved in language, social cognition, and reward. In contrast, stronger connections were observed between the centromedial and superficial subregions of the amygdala and brain regions involved in autonomic arousal, relaying sensory signals, and attention. Results of the correlational analyses showed that higher levels of anxiety were related with stronger connectivity with the hypothalamus, a brain region that influences autonomic and emotional responses. Higher levels of depression were associated with stronger connections to the insula, which is associated with emotional self-awareness and decision-making. In contrast, current autism severity was related to stronger connections with brain regions involved in autonomic arousal, relaying sensory signals, and attention and weaker connections with brain regions involved in cognitive control and introspection.