Abnormal functional connectivity (FC) within the fear network model (FNM) has been identified in panic disorder (PD) patients, but the specific local structural and functional properties, as well as effective connectivity (EC), remain poorly understood in PD. The purpose of this study was to investigate the structural and functional patterns of the FNM in PD. Magnetic resonance imaging data were collected from 33 PD patients and 35 healthy controls (HCs). Gray matter volume (GMV), degree centrality (DC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) were used to identify the structural and functional characteristics of brain regions within the FNM in PD. Subsequently, FC and EC of abnormal regions, based on local structural and functional features, and their correlation with clinical features were further examined. PD patients exhibited preserved GMV, ReHo, and ALFF in the brain regions of the FNM compared with HCs. However, increased DC in the bilateral amygdala was observed in PD patients. The amygdala and its subnuclei exhibited altered EC with rolandic operculum, insula, medial superior frontal gyrus, supramarginal gyrus, opercular part of inferior frontal gyrus, and superior temporal gyrus. Additionally, Hamilton Anxiety Scale score was positively correlated with EC from left lateral nuclei (dorsal portion) of amygdala to right rolandic operculum and left superior temporal gyrus. Our findings revealed a reorganized functional network in PD involving brain regions regulating exteroceptive-interoceptive signals, mood, and somatic symptoms. These results enhance our understanding of the neurobiological underpinnings of PD, suggesting potential biomarkers for diagnosis and targets for therapeutic intervention.

People who have suffered childhood trauma may be more susceptible to panic disorder (PD). Existing evidence indicates that childhood trauma can significantly impact brain function. Meanwhile, the brain regions involved in the fear network model (FNM) of PD highly overlap with the brain regions affected by childhood trauma. However, it remains unclear whether functional connections between brain regions associated with the FNM in patients with PD are affected by childhood trauma. This study aimed to investigate the effects of childhood trauma on the functional connectivity (FC) of brain regions associated with the FNM in patients with PD.
This study recruited 62 patients with PD, including 21 with a high level of childhood trauma (PD_HCT), 41 with a low level of childhood trauma (PD_LCT), and 40 healthy controls (HCs). The patients underwent magnetic resonance imaging resting-state scanning. The amygdala, anterior cingulate, thalamus, and hippocampus were chosen as regions of interest (ROIs) to examine group differences in ROIs and whole-brain resting-state FC (rsFC).
Compared with PD_HCT patients, PD_LCT patients exhibited significantly increased rsFC in the right thalamus, right temporo-occipital middle temporal gyrus, left thalamus, and right temporo-occipital middle temporal gyrus. Compared with HCs, PD_LCT patients had increased rsFC between the right thalamus and the right temporo-occipital middle temporal gyrus.
Patients with PD who had suffered high and low levels of childhood trauma were found to exhibit different pathological rsFC alterations in the FNM, suggesting that childhood trauma may be an important risk factor for the development of PD symptoms.

Background: Patients with panic disorder (PD) have an abnormal function in brain regions related to fear network is well recognised. However, the traditional fear network model (FNM) which was based on animals\' horrible behaviours has been found that it\'s not enough to explain the pathological mechanism of PD. This study aims to explore brain regions\' abnormalities in the new advanced FNM, and estimate whether it can better explain PD.Methods: Magnetic resonance imaging resting-state scans were acquired in 40 patients with PD (35 drug-naïve and 5 drug-free) and 40 healthy controls (HCs). Twelve brain regions in the advanced FNM were chosen as regions of interest (ROIs) to examine the group difference in the ROIs and whole-brain resting-state functional connectivity (rsFC).Results: We found significantly increased thalamic rsFC with the insula, compared with HCs. And it was significantly correlated with HAMA-somatic score. We also found increased thalamic rsFC with occipital gyrus, temporal gyrus, and frontal gyrus when compared with HCs.Conclusions: Taken together, PD patients exhibit abnormal rsFC alterations within the advanced FNM, especially the increased rsFC within thalamus-insula loop, suggesting that excessive sensitivity to external information plays an important role in PD. The advanced FNM may provide a fuller explanation about PD.

The core concept for pathophysiology in panic disorder (PD) is the fear network model (FNM). The alterations in FNM might be linked with disturbances in the autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional FNM included the frontal and limbic regions, which were dysregulated in the feedback mechanism for cognitive control of frontal lobe over the primitive response of limbic system. The exaggerated responses of limbic system are also associated with dysregulation in the neurotransmitter system. The neuroimaging studies also corresponded to FNM concept. However, more extended areas of FNM have been discovered in recent imaging studies, such as sensory regions of occipital, parietal cortex and temporal cortex and insula. The insula might integrate the filtered sensory information via thalamus from the visuospatial and other sensory modalities related to occipital, parietal and temporal lobes. In this review article, the traditional and advanced FNM would be discussed. I would also focus on the current evidences of insula, temporal, parietal and occipital lobes in the pathophysiology. In addition, the white matter and functional connectome studies would be reviewed to support the concept of advanced FNM. An emerging dysregulation model of fronto-limbic-insula and temporooccipito-parietal areas might be revealed according to the combined results of recent neuroimaging studies. The future delineation of advanced FNM model can be beneficial from more extensive and advanced studies focusing on the additional sensory regions of occipital, parietal and temporal cortex to confirm the role of advanced FNM in the pathophysiology of PD.