Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls

Abstract

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.

Functional neuroanatomy in panic disorder: Status quo of the research

“…Similarly to the results found by Engel et al[32], patients showed hyperactivation in an extended fear network comprising the brainstem, insula, thalamus, ACC, midcingulate cortex and DMPFC for disorder-related vs neutral scenes, compared to 26 healthy controls. No significant amygdala differences between groups could be found.…”

“…Engel et al[32] used pictures showing characteristic panic/agoraphobia situations to investigate activation differences in 19 PD patients in the predefined ROIs, i.e ., prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Greater activation in PD patients than in 21 controls was detected in the insula, left IFG, dorsomedial prefrontal cortex (DMPFC), the left hippocampal formation, and left caudatum, when panic-related and neutral scenes were compared.…”

“…Interestingly, two very recent studies using clear panic-related pictorial stimuli and relatively large sample sizes have put strong emphasis on a specific role of the insula and dACC in the pathophysiology of PD[29,32]. There is growing evidence that the insula, the dACC as well as subcortical structures, such as the amygdala, play a crucial role in salience processing across multiple sensory and cognitive domains by integrating external sensory information with internal emotional and bodily state signals[142].…”

Angst und Panik

“…Die Autoren verweisen darauf, dass Patienten oft insbesondere die Erwartungsangst ("Angst vor der Angst") beklagen. Engel et al [36] nutzten 20 individuelle störungsspezifische Bilder, die sie je 2-mal im Experiment präsentierten und verglichen deren Verarbeitung mit der Verarbeitung generell aversiver und neutraler Bilder. Bei Patienten im Vergleich zu gesunden Kontrollpersonen fanden sie eine stärkere Aktivierung im Hirnstamm auf panikspezifische im Vergleich zu generell aversiven Bildern, in der Insel fanden sie eine Mehraktivierung für panikspezifische im Vergleich zu neutralen Bildern.…”

Lower Functional Connectivity in Vestibular-Limbic Networks in Individuals With Subclinical Agoraphobia

“…The brain mechanisms presumed to underlie agoraphobic anxiety have been described extensively (46, 47). In recent neuroimaging studies, patients with panic disorder and agoraphobia showed greater activation than normal controls in the insular cortices bilaterally as well as in the left inferior frontal gyrus, dorsomedial pre-frontal cortex, caudate and hippocampus in response to exposure to symptom-specific pictures compared to healthy controls (48). Activations in the striatum and insula may be stronger in anticipation than actual viewing of agoraphobia-specific stimuli (49).…”