Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

BACKGROUND: Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. METHODS: The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). RESULTS: We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. LIMITATIONS: The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. CONCLUSION: Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

Brain activation to task-irrelevant disorder-related threat in social anxiety disorder: The impact of symptom severity.

Unintentional and uncontrollable processing of threat has been suggested to contribute to the pathology of social anxiety disorder (SAD). The present study investigated the neural correlates of processing task-irrelevant, highly ecologically valid, disorder-related stimuli as a function of symptom severity in SAD. Twenty-four SAD patients and 24 healthy controls (HC) performed a feature-based comparison task during functional magnetic resonance imaging, while task-irrelevant, disorder-related or neutral scenes were presented simultaneously at a different spatial position. SAD patients showed greater activity than HC in response to disorder-related versus neutral scenes in brain regions associated with self-referential processing (e.g. insula, precuneus, dorsomedial prefrontal cortex) and emotion regulation (e.g. dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus). Symptom severity was positively associated with amygdala activity, and negatively with activation in dorsal anterior cingulate cortex and dlPFC in SAD patients. Additional correlation analysis revealed that amygdala-prefrontal coupling was positively associated with symptom severity. A network of brain regions is thus involved in SAD patients' processing of task-irrelevant, complex, ecologically valid, disorder-related scenes. Furthermore, increasing symptom severity in SAD patients seems to reflect a growing imbalance between neural mechanisms related to stimulus-driven bottom-up and regulatory top-down processes resulting in dysfunctional regulation strategies.

Brain responses to disorder-related visual threat in panic disorder.

Panic disorder (PD) patients show aberrant neural responses to threatening stimuli in an extended fear network, but results are only partially comparable, and studies implementing disorder-related visual scenes are lacking as stimuli. The neural responses and functional connectivity to a newly developed set of disorder-related, ecologically valid scenes as compared with matched neutral visual scenes, using event-related functional magnetic resonance imaging (fMRI) in 26 PD patients and 26 healthy controls (HC) were investigated. PD patients versus HC showed hyperactivation in an extended fear network comprising brainstem, insula, thalamus, anterior, and mid-cingulate cortex and (dorso-)medial prefrontal cortex for disorder-related versus neutral scenes. Amygdala differences between groups failed significance. Subjective levels of anxiety significantly correlated with brainstem activation in PD patients. Analysis of functional connectivity by means of beta series correlation revealed no emotion-specific alterations in connectivity in PD patients versus HC. The results suggest that subjective anxiety evoked by external stimuli is directly related to altered activation in the homeostatic alarm system in PD. With novel disorder-related stimuli, the study sheds new light on the neural underpinnings of pathological threat processing in PD. Hum Brain Mapp 37:4439-4453, 2016. © 2016 Wiley Periodicals, Inc.

Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder.

Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder-related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies.