Changjian Qiu

Selective aberrant functional connectivity of resting state networks in social anxiety disorder.

Several functional MRI (fMRI) activation studies have highlighted specific differences in brain response in social anxiety disorder (SAD) patients. Little is known, so far, about the changes in the functional architecture of resting state networks (RSNs) in SAD during resting state. We investigated statistical differences in RSNs on 20 SAD and 20 controls using independent component analysis. A diffuse impact on widely distributed RSNs and selective changes of RSN intrinsic functional connectivity were observed in SAD. Functional connectivity was decreased in the somato-motor (primary and motor cortices) and visual (primary visual cortex) networks, increased in a network including medial prefrontal cortex which is thought to be involved in self-referential processes, and increased or decreased in the default mode network (posterior cingulate cortex/precuneus, bilateral inferior parietal gyrus, angular gyrus, middle temporal gyrus, and superior and medial frontal gyrus) which has been suggested to be involved in episodic memory, and self-projection, the dorsal attention network (middle and superior occipital gyrus, inferior and superior parietal gyrus, and middle and superior frontal gyrus) which is thought to mediate goal-directed top-down processing, the core network (insula-cingulate cortices) which is associated with task control function, and the central-executive network (fronto-parietal cortices). A relationship between functional connectivity and disease severity was found in specific regions of RSNs, including medial and lateral prefrontal cortex, as well as parietal and occipital regions. Our results might supply a novel way to look into neuro-pathophysiological mechanisms in SAD patients.

Altered Effective Connectivity Network of the Amygdala in Social Anxiety Disorder: A Resting-State fMRI Study

The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds “normally” to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder.

Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder ☆

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFC). Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyrus. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD.

Regional homogeneity changes in social anxiety disorder: A resting-state fMRI study

The previous task-based or resting perfusion studies in social anxiety disorder (SAD) patients have highlighted specific differences in brain response. Little is known about the changes in the local synchronization of spontaneous functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signals that occur in SAD during the resting state. We investigated altered neural activity in the resting state using a regional homogeneity (ReHo) analysis on 20 SAD and 20 healthy controls (HC). Compared with HC, SAD patients exhibited decreased coherence (ReHo) in the bilateral angular gyrus and the left medial prefrontal cortex within the default mode network (DMN), suggesting functional impairment of the perception of socially relevant emotional state and self-related mental representations; and also in the right dorsolateral prefrontal cortex and right inferior parietal gyrus within the central-executive network (CEN), reflecting the deficit of cognitive control of social anxiety. Significantly increased coherence (ReHo) was found in the left middle occipital gyrus, which would be consistent with their hypervigilance and hyperprosexia to the social communication even in the resting state. Our results might supply a novel way to look into neuro-pathophysiological mechanisms in SAD patients.

Disrupted functional connectivity in social anxiety disorder: a resting-state fMRI study

Dysfunction of the corticolimbic circuitry has been highlighted in social anxiety disorder (SAD) during social stimuli. However, few studies have investigated functional connectivity in SAD during the resting state, which may improve our understanding of SAD pathophysiology. The aim of this study was to investigate whether whole-brain functional connectivity might be aberrant in SAD patients, and if so, whether these changes are related to the measured clinical severity. Seventeen SAD patients and 19 healthy controls participated in resting-state functional magnetic resonance imaging. The brain was first divided into 90 paired brain regions and functional connectivity was then estimated by temporal correlation between each of these regions. Furthermore, connections that were significantly disrupted in SAD patients were correlated with clinical severity measured using the Liebowitz Social Anxiety Scale. Compared with healthy controls, SAD patients showed decreased positive connections within the frontal lobe and decreased negative connections between the frontal and occipital lobes. In particular, the weaker negative connections between the frontal lobe, which mainly involved the right median prefrontal cortex, and the occipital lobe had a significant positive correlation with the severity of SAD symptoms. The results support the hypothesis that some abnormalities of functional connectivity exist in SAD patients, which relate to the frontal cortex and occipital cortex. In addition, decreased functional connectivity between the frontal and occipital lobes and within the frontal lobe might be related to abnormal information processing and reflect disturbed neural organization resulting in defective social cognition, which could represent an early imaging biomarker for SAD.

Anatomical deficits in adult posttraumatic stress disorder: A meta-analysis of voxel-based morphometry studies

Evidence from previous anatomical studies indicate that widespread brain regions are involved in the pathogenesis of posttraumatic stress disorder (PTSD). The aim of the present study was to quantitatively integrate the literature on structural abnormalities seen on individuals with PTSD. Twenty voxel-based analysis studies were analysed through a comprehensive series of meta-analyses. Compared with healthy controls, PTSD patients showed a significant reduction in grey matter (GM) in the left anterior cingulate gyrus (ACC) at the whole-brain level. Several brain regions, including the left ACC, the left insula and the right parahippocampal gyrus were significantly smaller in individuals with PTSD than in trauma-exposed healthy subjects. Furthermore, the clinician-administered PTSD scale scores were negatively correlated with GM in the left ACC and positively correlated with GM in the left insula. In addition, PTSD patients who experienced accidental or non-accidental trauma had anatomical changes in different brain regions. These results suggest that the smaller ACC and insular cortex within the limbic-prefrontal circuit contribute to the pathogenesis of PTSD. Moreover, the PTSD patients with different types of trauma may have different cerebral deficits.

Neuroanatomical deficits in drug-naïve adult patients with generalized social anxiety disorder: a voxel-based morphometry study.

Little is known, so far, about the cerebral structural deficits in drug-naïve adult social anxiety disorder (SAD) patients. The present study aimed to explore the cerebral anatomic deficits in drug-naïve adult generalized SAD patients using voxel-based morphometric analysis with DARTEL. High-resolution T1-weighted images were acquired from 20 drug-naïve adult SAD patients and 19 age-, sex- and education-matched controls. The volumes of gray matter, white matter, cerebrospinal fluid, and total intracranial volume were compared between groups using two-sample t-tests with age and gender as covariates. Gray matter density (GMD) was compared between groups using voxel-wise two-sample t-test analysis. Correlation analysis was used to identify any associations between regional GMD and clinical symptoms. Compared with healthy controls, SAD patients showed significantly lower GMD in the bilateral thalami, right amygdala, and right precuneus. Furthermore, the GMD in the right amygdala was negatively related to the disease duration, but positively correlated with age of onset. Our findings demonstrated that cerebral anatomic deficits could be found within limbic and thalamic areas in drug-naïve SAD patients, which provides structural information to complement the functional alterations observed in the same regions.

Alterations in Low-Level Perceptual Networks Related to Clinical Severity in PTSD after an Earthquake: A Resting-State fMRI Study

Background Several task-based functional MRI (fMRI) studies have highlighted abnormal activation in specific regions involving the low-level perceptual (auditory, visual, and somato-motor) network in posttraumatic stress disorder (PTSD) patients. However, little is known about whether the functional connectivity of the low-level perceptual and higher-order cognitive (attention, central-execution, and default-mode) networks change in medication-naïve PTSD patients during the resting state. Methods We investigated the resting state networks (RSNs) using independent component analysis (ICA) in 18 chronic Wenchuan earthquake-related PTSD patients versus 20 healthy survivors (HSs). Results Compared to the HSs, PTSD patients displayed both increased and decreased functional connectivity within the salience network (SN), central executive network (CEN), default mode network (DMN), somato-motor network (SMN), auditory network (AN), and visual network (VN). Furthermore, strengthened connectivity involving the inferior temporal gyrus (ITG) and supplementary motor area (SMA) was negatively correlated with clinical severity in PTSD patients. Limitations Given the absence of a healthy control group that never experienced the earthquake, our results cannot be used to compare alterations between the PTSD patients, physically healthy trauma survivors, and healthy controls. In addition, the breathing and heart rates were not monitored in our small sample size of subjects. In future studies, specific task paradigms should be used to reveal perceptual impairments. Conclusions These findings suggest that PTSD patients have widespread deficits in both the low-level perceptual and higher-order cognitive networks. Decreased connectivity within the low-level perceptual networks was related to clinical symptoms, which may be associated with traumatic reminders causing attentional bias to negative emotion in response to threatening stimuli and resulting in emotional dysregulation.

Altered spontaneous neuronal activity of visual cortex and medial anterior cingulate cortex in treatment-naïve posttraumatic stress disorder

BACKGROUND Although no more traumatic stimuli exists, a variety of symptoms are persisting in chronic Posttraumatic Stress Disorder (PTSD) patients. It is therefore necessary to explore the spontaneous brain activity of treatment-naïve PTSD patients during resting-state. METHOD Seventeen treatment-naïve PTSD patients and twenty traumatized controls were recruited and underwent a resting functional magnetic resonance imaging (Rs-fMRI) scan. The differences of regional brain spontaneous activity between the participants with and without PTSD were measured by Amplitude of Low-frequency fluctuation (ALFF). The relationship between the altered brain measurements and the symptoms of PTSD were analyzed. RESULT Compared to traumatized controls, the PTSD group showed significantly altered ALFF in many emotion-related brain regions, such as the medial anterior cingulate cortex (MACC), dorsolateral prefrontal cortex (DLPFC), insular (IC), middle temporal gyrus (MTG), and ventral posterior cingulate cortex (VPCC). Interestingly this is the first report of a hyperactive visual cortex (V1/V2) during resting-state in treatment-naïve PTSD patients. There were significant positive correlations between ALFF values in the bilateral visual cortex and re-experiencing or avoidance in PTSD. Negative correlation was observed between ALFF values in MACC and avoidance. CONCLUSION This study suggested that the visual cortex and the MACC may be involved in the characteristic symptoms of chronic PTSD, such as re-experiencing and avoidance. Future studies that focus on these areas of the brain are required, as alteration of these areas may act as a biomarker and could be targeted in future treatments for PTSD.

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

Objective We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD. Methods We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed. Results Our findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus. Conclusion These results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.