Increased Neural Habituation in the Amygdala and Orbitofrontal Cortex in Social Anxiety Disorder Revealed by fMRI

Abstract

A characterizing symptom of social anxiety disorder (SAD) is increased emotional reactivity towards potential social threat in combination with impaired emotion and stress regulation. While several neuroimaging studies have linked SAD with hyperreactivity in limbic brain regions when exposed to emotional faces, little is known about habituation in both the amygdala and neocortical regulation areas. 15 untreated SAD patients and 15 age- and gender-matched healthy controls underwent functional magnetic resonance imaging during repeated blocks of facial emotion () and object discrimination tasks (). Emotion processing networks were defined by a task-related contrast (). Linear regression was employed for assessing habituation effects in these regions. In both groups, the employed paradigm robustly activated the emotion processing and regulation network, including the amygdalae and orbitofrontal cortex (OFC). Statistically significant habituation effects were found in the amygdalae, OFC, and pulvinar thalamus of SAD patients. No such habituation was found in healthy controls. Concurrent habituation in the medial OFC and the amygdalae of SAD patients as shown in this study suggests intact functional integrity and successful short-term down-regulation of neural activation in brain areas responsible for emotion processing. Initial hyperactivation may be explained by an insufficient habituation to new stimuli during the first seconds of exposure. In addition, our results highlight the relevance of the orbitofrontal cortex in social anxiety disorders.

Amygdala habituation: A reliable fMRI phenotype

“…Here differences between low and high scoring subjects have been shown for both amygdala activation (Calder et al, 2011) and habituation (Sladky et al, 2012).…”

Hyper-Connectivity of Subcortical Resting-State Networks in Social Anxiety Disorder

“…Enhanced connectivity in pre-motor regions suggests that SAD patients are in a state of "motor readiness", either due to abnormal input to the striatum (from amygdala or mid-brain dopaminergic neurons) as proposed as a testable model for anxiety disorders by (Marchand, 2010). Enhanced functional connectivity with striatum and regions of the OFC with SAD is equally interesting because of recent reports from task-based fMRI, highlighting the role of OFC in neural habituation in SAD (Sladky et al, 2012).…”

Emotion Regulation and Trait Anxiety Are Predicted by the Microstructure of Fibers between Amygdala and Prefrontal Cortex

“…Given accumulating evidence for an asymmetric involvement of the PFC, with a right-hemispheric dominance for anxiety and anxiety-related processes ( and Landers, 1994;Lucey et al, 1995;Stapleton et al, 1997;Bremner et al, 1999;Nitschke et al, 1999;Wiedemann et al, 1999;Davidson et al, 2000;Davidson, 2002;Pizzagalli et al, 2002;Smit et al, 2007, Harmon-Jones et al, 2010, we expected our structural trait anxiety effects to be particularly visible in the right hemisphere. Based on evidence for a left-hemispheric lateralization of reappraisal use (Ochsner et al, 2002;Jackson et al, 2003;Kim and Bell, 2006) and recently observed left-sided biases of metabolic activity in the superior frontal gyrus in frequent reappraisers (Kim et al, 2012), we expected reappraisal use effects to be most prominent in the left hemisphere.…”

“…Based on the literature, four regions in the PFC were defined: the ventromedial PFC (vmPFC; Buckholtz et al, 2008), the dorsomedial PFC (dmPFC; Kim et al, 2011), the dorsolateral PFC (dlPFC; Stein et al, 2007), and the OFC (Zald and Kim, 1996a,b;Rauch et al, 1997;Sladky et al, 2012). Since the precise anatomical locations and boundaries of these areas have not yet been defined beyond controversy (Roy et al, 2012), there was no suitable ready-to-use atlas that comprised all four PFC areas for our purposes.…”