Uncovering the global task-modulated brain network in chunk decomposition with Chinese characters.

Chunk decomposition, which requires the mental representation transformation in accordance with behavioral goals, is of vital importance to problem solving and creative thinking. Previous studies have identified that the frontal, parietal, and occipital cortex in the cognitive control network selectively activated in response to chunk tightness, however, functional localization strategy may overlook the interaction brain regions. Based on the notion of a global brain network, we proposed that multiple specialized regions have to be interconnected to maintain goal representation during the course of chunk decomposition. Therefore, the present study applied a beta-series correlation method to investigate interregional functional connectivity in the event-related design of chunk decomposition tasks using Chinese characters, which would highlight critical nodes irrespective to chunk tightness. The results reveal a network of functional hubs with highly within or between module connections, including the orbitofrontal cortex, superior/inferior parietal lobule, hippocampus, and thalamus. We speculate that the thalamus integrates information across modular as an integrative hub while the orbitofrontal cortex tracks the mental states of chunk decomposition on a moment-to-moment basis. The superior and inferior parietal lobule collaborate to manipulate the mental representation of chunk decomposition and the hippocampus associates the relationship between elements in the question and solution phase. Furthermore, the tightness of chunks is not only associated with different processors in visual systems but also leads to increased intermodular connections in right superior frontal gyrus and left precentral gyrus. To summary up, the present study first reveals the task-modulated brain network of chunk decomposition in addition to the tightness-related nodes in the frontal and occipital cortex.

Insula shows abnormal task-evoked and resting-state activity in first-episode drug-naïve generalized anxiety disorder.

BACKGROUND: Interoception is associated with neural activity in the insula of healthy humans. On the basis of the somatic symptoms in generalized anxiety disorder (GAD), especially abnormal heartbeat perception, we hypothesized that abnormal activity in the insula was associated with interoceptive awareness in patients with GAD. METHODS: We investigated the psychological correlates of interoceptive awareness in a sample of 34 patients with first-onset, drug-naïve GAD and 30 healthy controls (HCs). Furthermore, we compared blood oxygenation level-dependent responses between the two groups during a heartbeat perception task to assess task-evoked activity and its relationship with psychological measures. We also examined between-group differences in insular subregions resting-state functional connectivity (rsFC), and its relationship with anxiety severity. RESULTS: Patients with GAD had significantly higher body perception scores than HCs. They also exhibited greater task-evoked activity in the left anterior insula, left posterior insula, and right anterior insula during interoceptive awareness than HCs. Left anterior insula activity was positively correlated with body awareness in patients with GAD, and rsFC between the left anterior insula and left medial prefrontal gyrus was negatively correlated with somatic anxiety severity. CONCLUSIONS: Investigating a sample of first-episode, drug-naïve patients, our study demonstrated abnormal interoceptive awareness in patients with GAD and that this was related to abnormal anterior insular activity during both rest and task. These results shed new light on the psychological and neural substrates of somatic symptoms in GAD, and they may serve to establish abnormal interoceptive awareness as a neural and psychological marker of GAD.

Probing the Cognitive Mechanism of Mental Representational Change During Chunk Decomposition: A Parametric fMRI Study.

Chunk decomposition plays an important role in cognitive flexibility in particular with regards to representational change, which is critical for insight problem solving and creative thinking. In this study, we investigated the cognitive mechanism of decomposing Chinese character chunks through a parametric fMRI design. Our results from this parametric manipulation revealed widely distributed activations in frontal, parietal, and occipital cortex and negative activations in parietal and visual areas in response to chunk tightness during decomposition. To mentally manipulate the element of a given old chunk, superior parietal lobe appears to support element restructuring in a goal-directed way, whereas the negatively activated inferior parietal lobe may support preventing irrelevant objects from being attended. Moreover, determining alternative ways of restructuring requires a constellation of frontal areas in the cognitive control network, such as the right lateral prefrontal cortex in inhibiting the predominant chunk representations, the presupplementary motor area in initiating a transition of mental task set, and the inferior frontal junction in establishing task sets. In conclusion, this suggests that chunk decomposition reflects mental transformation of problem representation from an inappropriate state to a new one alongside with an evaluation of novel and insightful solutions by the caudate in the dorsal striatum.

Feasibility of applying graph theory to diagnosing generalized anxiety disorder using machine learning models.

The aim of this study was to investigate whether the alterations of topological properties can facilitate the diagnosis of generalized anxiety disorder (GAD). Twenty first-episode drug-naive Chinese individuals with GAD and twenty age-sex-education-matched healthy controls (HCs) were included in the primary training set, and the results of which were validated using nineteen drug-free patients with GAD and nineteen unmatched HCs. Two 3 T scanners were used to acquire T1, diffusion tensor, and resting-state functional images. Topological properties were altered in the functional cerebral networks among patients with GAD, but not in the structural networks. Using the nodal topological properties in the anti-correlated functional networks, machine learning models distinguished drug-naive GADs from their matched HCs independent of the type of kernels and the amount of features. Although the models built with drug-naive GADs failed to distinguish drug-free GADs from HCs, the features selected for those models could be used to build new models for distinguishing drug-free GADs from HCs. Our findings suggested that it is feasible to utilize the topological characteristics of brain network to facilitate the diagnosis of GAD. However, further research with decent sample sizes, multimodal features, and improved modeling methods are needed to build more robust models.

Specific and common functional connectivity deficits in drug-free generalized anxiety disorder and panic disorder: A data-driven analysis.

Evidence of comparing neural network differences between anxiety disorder subtypes is limited, while it is crucial to reveal the pathogenesis of anxiety disorders. The present study aimed to investigate specific and common resting-state functional connectivity (FC) networks in generalized anxiety disorder (GAD), panic disorder (PD), and healthy controls (HC). We employed the gRAICAR algorithm to decompose the resting-state fMRI into independent components and align the components across 61 subjects (22 GAD, 18 PD and 21 HC). The default mode network and precuneus network exhibited GAD-specific aberrance, the anterior default mode network showed atypicality specific to PD, and the right fronto-parietal network showed aberrance common to GAD and PD. Between GAD-specific networks, FC between bilateral dorsolateral prefrontal cortex (DLPFC) was positively correlated with interoceptive sensitivity. In the common network, altered FCs between DLPFC and angular gyrus, and between orbitofrontal cortex and precuneus, were positively correlated with anxiety severity and interoceptive sensitivity. The pathological mechanism of PD could closely relate to the dysfunction of prefrontal cortex, while GAD could involve more extensive brain areas, which may be related to fear generalization.

Chinese patients' response to doctor-patient relationship stimuli: evidence from an event-related potential study.

BACKGROUND: With improvements in medical technology, the doctor-patient relationship should be further improved. However, disputes between doctors and patients have increased, with the two groups frequently hurting each other. Therefore, we sought to explore the perception of Chinese patients regarding the stimuli of doctor-patient relationships with different valence. METHODS: We used event-related potential (ERP) to explore the brain electrical activity of 19 undergraduate participants who had a clinical experience in the previous 6 months where they perceived negative, neutral, and positive doctor-patient relationships. The ERPs were recorded, and the early ERP components (P2) and late positive potential (LPP) were measured. RESULTS: Compared with the stimuli of negative doctor-patient relationships, those of positive doctor-patient relationships would attract more attention and have larger P2 amplitude; LPP was larger for the stimuli of negative doctor-patient relationships than neutral ones in the 500-800 ms, while in the 1100-1500 ms, the stimuli of neutral doctor-patient relationships elicited larger LPP amplitude than positive ones. CONCLUSION: Patients paid more attention to the stimuli of positive doctor-patient relationships because they expected to have the same positive relationship. Although threatening elements in negative doctor-patient relationships would catch patients' attention and make them have implicit emotional regulation, neutral stimuli with poker-faced doctors would cause lasting attention. These results illustrate the patients' real perception of the different valence of doctor-patient relationship stimuli.

Altered heartbeat perception sensitivity associated with brain structural alterations in generalised anxiety disorder.

BACKGROUND: Palpitation is a common complaint in generalised anxiety disorder (GAD). Brain imaging studies have investigated the neural mechanism of heartbeat perception in healthy volunteers. This study explored the neuroanatomical differences of altered heartbeat perception in patients with GAD using structural MRI. AIMS: Based on the strong somatic-interoceptive symptoms in GAD, we explored the regional structural brain abnormalities involved in heartbeat perception in patients with GAD. METHODS: This study was applied to the a priori regions using neuroanatomical theories of heartbeat perception, including the insula, anterior cingulate cortex, supplementary motor area and prefrontal cortex. A total of 19 patients with GAD and 19 healthy control subjects were enrolled. We used the FMRIB Software Library voxel-based morphometry software for estimating the grey matter volume of these regions of interest and analysed the correlation between heartbeat perception sensitivity and the volume of abnormal grey matter. RESULTS: Patients with GAD showed a significantly decreased volume of grey matter in their left medial prefrontal cortex, right orbital frontal cortex and anterior cingulate cortex. The grey matter volume of the left medial prefrontal cortex negatively correlated with heartbeat perception sensitivity in patients with GAD. CONCLUSIONS: It should be the first study that shows heartbeat perception is associated with brain structure in GAD. Our findings suggest that the frontal region may play an important role in aberrant heartbeat perception processing in patients with GAD, and this may be an underlying mechanism resulting in the abnormal cardiovascular complaints in GAD. This is hypothesised as a 'top-down' deficiency, especially in the medial prefrontal cortex. This will provide the foundation for a more targeted region for neuromodulation intervention in the future.

Efficacy and safety of repetitive transcranial magnetic stimulation for generalised anxiety disorder: A meta-analysis.

BACKGROUND: Pharmacological and conventional non-pharmacological treatments are only moderately effective in treating generalised anxiety disorder (GAD). Recently, repetitive transcranial magnetic stimulation (rTMS) has attracted interest because of its potential therapeutic value. AIM: To investigate the efficacy and safety of rTMS treatment for GAD. METHODS: Literature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018. The included studies' bias risk was assessed using Cochrane risk of bias assessment tool. Meta-analysis was performed to compute the standardised mean difference (SMD) and risk ratio (RR) along with its 95% CIs through using RevMan V.5.3. Heterogeneity was inspected by I2 and the χ2 test. We performed subgroup analysis and meta-regression to investigate heterogeneity. We used funnel plot to assess publication bias. We used the GRADE approach to assess the whole quality of evidence. RESULTS: Twenty-one studies, with a total sample size of 1481, were analysed. The risk of bias in most studies included is moderate, the majority of which are lacking of blinding methods of treatment allocation. The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score (SMD=-0.68; 95% CI -0.89 to -0.46). None of the 21 studies included here reported severe adverse events. As for dropout rates, there are no statistically significant differences between the two groups (RR 1.14, 95% CI 0.72 to 1.82) or adverse events (RR 0.95, 95% CI 0.77 to 1.18). No particular influence on the heterogeneity of any variable was observed. The risk of publication bias was low. According to the GRADE approach, the evidence levels of primary outcome (treatment effects) and secondary outcomes (acceptability and safety) were rated as 'medium'. CONCLUSION: The use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD. However, we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis. Future high-quality clinical trials are needed to confirm our results.

Altered Interoceptive Processing in Generalized Anxiety Disorder-A Heartbeat-Evoked Potential Research.

Generalized anxiety disorder (GAD) is one of the most common anxiety disorders. The brain's dysfunctional processing of interoceptive information is increasingly recognized as an important component of anxiety disorders. However, the neural mechanisms remain insufficiently understood. In the present study, patients with GAD and healthy control participants underwent an eyes-closed (EC) resting state (interoception) and eyes-open (EO) resting state (exteroception) without paying conscious attention to heartbeat. Electrocardiography (ECG) and electroencephalography (EEG) signals were recorded at the same time. The results show that in healthy controls, the heartbeat-evoked brain potential (HEP) was modulated by the conditions, with a significantly higher amplitude under EC than EO, while this was not the case in GAD patients. Further analysis revealed that the dysfunction of HEP modulation in GAD patients may be attributed to excessive interoceptive processing under EO, with a marginally higher HEP in GAD than in the healthy controls. Finally, the right prefrontal HEP amplitude during EC condition was significantly correlated with the severity of the patients' anxiety symptoms. Our results suggest that altered cortical processing of interoceptive signals may play an important role in the pathophysiology of generalized anxiety disorder.

Resolving the Electroencephalographic Correlates of Rapid Goal-Directed Chunking in the Frontal-Parietal Network.

Previous studies have revealed a specific role of the prefrontal-parietal network in rapid goal-directed chunking (RGDC), which dissociates prefrontal activity related to chunking from parietal working memory demands. However, it remains unknown how the prefrontal and parietal cortices collaborate to accomplish RGDC. To this end, a novel experimental design was used that presented Chinese characters in a chunking task, testing eighteen undergraduate students (9 females, mean age = 22.4 years) while recoding the electroencephalogram (EEG). In the experiment, radical-level chunking was accomplished in a timely stringent way (RT = 1485 ms, SD = 371 ms), whereas the stroke-level chunking was accomplished less coherently (RT = 3278 ms, SD = 1083 ms). By comparing the differences between radical-level chunking vs. stroke-level chunking, we were able to dissociate the chunking processes in the radical-level chunking condition within the analyzed time window (-200 to 1300 ms). The chunking processes resulted in an early increase of gamma band synchronization over parietal and occipital cortices, followed by enhanced power in the beta-gamma band (25-38 Hz) over frontal areas. We suggest that the posterior rhythmic activities in the gamma band may underlie the processes that are directly associated with perceptual manipulations of chunking, while the subsequent beta-gamma activation over frontal areas appears to reflect a post-evaluation process such as reinforcement of the selected rules over alternative solutions, which may be an important characteristic of goal-directed chunking.

Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review.

BACKGROUND: Negative symptoms are one of the most difficult areas in the treatment of schizophrenia because antipsychotics are often less effective towards them. Repetitive transcranial magnetic stimulation (rTMS) is a new technique for cerebral cortex stimulation and is believed to be a safe and promising method for the treatment of mental disorders. As the clinical research and new treatment models have increased in recent years, the efficacy towards negative symptoms and safety evaluation of rTMS treatment should also be updated. AIMS: To explore the efficacy and safety of rTMS in the treatment of negative symptoms for patients with schizophrenia. METHODS: We searched for relevant controlled clinical trials from the following databases: PubMed, EMBASE, the Cochrane Library, EBSCO, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SINOMED, and Airiti Library. The retrieval time went up to January 2, 2017. The research literature was screened according to the predefined inclusion and exclusion criteria. After data extraction, statistical analysis was conducted by using RevMan 5.3 and Stata 14. Quality evaluation was done on the included research articles. The Cochrane risk of bias assessment tool was adopted for assessing risk of bias. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used as the reference standard. RESULTS: A total of 3500 articles were retrieved. In the end, there were 29 articles included in the metaanalysis with a total sample size of 1440. After the meta-analysis, it was found that the use of antipsychotic treatment combined with rTMS could improve the negative symptoms of patients (SMD=-0.40, 95% CI= -0.62~-0.18). Based on the bias of the efficacy evaluation assessed by the Cochrane risk of bias assessment tool, there were 6 studies rated as having "high risk of bias" and the rest were rated as "unable to determine". According to the assessment, development and evaluation criteria of the GRADE classification, the evidence quality for the efficacy evaluation index was "moderate". The acceptability of rTMS treatment was better (RR= 0.75, 95% CI= 0.49~1.15, based on the 1492 samples from the 28 studies), however, the patients who received the rTMS treatment had a higher rate of mild adverse effects (RR= 2.20, 95% CI= 1.53~ 3.18, based on the 1296 samples from the 23 studies). CONCLUSIONS: The use of the antipsychotic treatment incorporated with rTMS treatment can slightly improve the negative symptoms of patients with schizophrenia and has better acceptability and fewer adverse effects. Nevertheless, there is publication bias in this study and the heterogeneity of the study is relatively high. Therefore, we need to be cautious when interpreting the results.