Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder. Cui Huiru,Zhang Jie,Liu Yicen,Li Qingwei,Li Hui,Zhang Lanlan,Hu Qiang,Cheng Wei,Luo Qiang,Li Jianqi,Li Wei,Wang Jijun,Feng Jianfeng,Li Chunbo,Northoff Georg Human brain mapping Generalized anxiety disorder (GAD) and panic disorder (PD) are most common anxiety disorders with high lifetime prevalence while the pathophysiology and disease-specific alterations still remain largely unclear. Few studies have taken a whole-brain perspective in the functional connectivity (FC) analysis of these two disorders in resting state. It limits the ability to identify regionally and psychopathologically specific network abnormalities with their subsequent use as diagnostic marker and novel treatment strategy. The whole brain FC using a novel FC metric was compared, that is, scaled correlation, which they demonstrated to be a reliable FC statistics, but have higher statistical power in two-sample t-test of whole brain FC analysis. About 21 GAD and 18 PD patients were compared with 22 matched control subjects during resting-state, respectively. It was found that GAD patients demonstrated increased FC between hippocampus/parahippocampus and fusiform gyrus among the most significantly changed FC, while PD was mainly associated with greater FC between somatosensory cortex and thalamus. Besides such regional specificity, it was observed that psychopathological specificity in that the disrupted FC pattern in PD and GAD correlated with their respective symptom severity. The findings suggested that the increased FC between hippocampus/parahippocampus and fusiform gyrus in GAD were mainly associated with a fear generalization related neural circuit, while the greater FC between somatosensory cortex and thalamus in PD were more likely linked to interoceptive processing. Due to the observed regional and psychopathological specificity, their findings bear important clinical implications for the potential treatment strategy. 10.1002/hbm.23113

Aberrant limbic and salience network resting-state functional connectivity in panic disorder without comorbidity. Pannekoek Justine Nienke,Veer Ilya M,van Tol Marie-José,van der Werff Steven J A,Demenescu Liliana R,Aleman André,Veltman Dick J,Zitman Frans G,Rombouts Serge A R B,van der Wee Nic J A Journal of affective disorders BACKGROUND:Panic disorder (PD) is a prevalent and debilitating disorder but its neurobiology is still poorly understood. We investigated resting-state functional connectivity (RSFC) in PD without comorbidity in three networks that have been linked to PD before. This could provide new insights in how functional integration of brain regions involved in fear and panic might relate to the symptomatology of PD. METHODS:Eleven PD patients without comorbidity and eleven pair-wise matched healthy controls underwent resting-state fMRI. We used seed regions-of-interest in the bilateral amygdala (limbic network), the bilateral dorsal anterior cingulate cortex (dACC) (salience network), and the bilateral posterior cingulate cortex (default mode network). RSFC of these areas was assessed using seed-based correlations. All results were cluster corrected for multiple comparisons (Z>2.3, p<.05). RESULTS:Abnormalities were identified in the limbic network with increased RSFC between the right amygdala and the bilateral precuneus in PD patients. In the salience network the dACC demonstrated altered connectivity with frontal, parietal and occipital areas. LIMITATIONS:The small sample size and hypothesis-driven approach could restrict finding additional group differences that may exist. Other caveats are reflected in the use of medication by two participants and the acquisition of the resting-state scan at the end of a fixed imaging protocol. CONCLUSION:We found altered RSFC in PD between areas involved in emotion regulation and emotional and somatosensory stimulus processing, as well as an area engaged in self-referential processing, not implicated in models for PD before. These findings extend existing functional neuroanatomical models of PD, as the altered RSFC may underlie increased sensitivity for bodily symptoms. 10.1016/j.jad.2012.07.006

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder. Journal of psychiatry & neuroscience : JPN 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. 10.1503/jpn.160226

Altered resting-state network connectivity in panic disorder: an independent ComponentAnalysis. Brain imaging and behavior Panic disorder (PD) is a prevalent anxiety disorder but its neurobiology remains poorly understood. It has been proposed that the pathophysiology of PD is related to an abnormality in a particular neural network. However, most studies investigating resting-state functional connectivity (FC) have relied on a priori restrictions of seed regions, which may bias observations. This study investigated changes in intra and internetwork FC in the whole brain of patients with PD using resting-state functional magnetic resonance imaging. A voxel-wise data-driven independent component analysis was performed on 26 PD patients and 27 healthy controls (HCs).We compared the differences in the intra and internetwork FC between the two groups of subjects using statistical parametric mapping with two-sample t-tests. PD patients exhibited decreased intra-network FC in the right anterior cingulate cortex (ACC) of the anterior default mode network, the left precentral and postcentral gyrus of the sensorimotor network, the right lobule V/VI, the cerebellum vermis, and the left lobule VI of the cerebellum network compared with the HCs. The intra-network FC in the right ACC was negatively correlated with symptom severity. None of the pairs of resting state networks showed significant differences in functional network connectivity between the two groups. These results suggest that the brain networks associated with emotion regulation, interoceptive awareness, and fear and somatosensory processing may play an important role in the pathophysiology of PD. 10.1007/s11682-020-00329-z