A connectome-based model of delusion in schizophrenia using functional connectivity under working memory task.

Delusion is an important feature of schizophrenia, which may stem from cognitive biases. Working memory (WM) is the core foundation of cognition, closely related to delusion. However, the knowledge of neural mechanisms underlying the relationship between WM and delusion in schizophrenia is poorly investigated. Two hundred and thirty patients with schizophrenia (dataset 1: n = 130; dataset 2: n = 100) were enrolled and scanned for an N-back WM task. We constructed the WM-related whole-brain functional connectome and conducted Connectome-based Predictive Modelling (CPM) to detect the delusion-related networks and built the correlation model in dataset 1. The correlation between identified networks and delusion severity was tested in a separate, heterogeneous sample of dataset 2 that mainly includes early-onset schizophrenia. The identified delusion-related network has a strong correlation with delusion severity measured by the NO.20 item of SAPS in dataset 1 (r = 0.433, p = 2.7 × 10-7, permutation-p = 0.035), and can be validated in the same dataset by using another delusion measurement, that is, the P1 item of PANSS (r = 0.362, p = 0.0005). It can be validated in another independent dataset 2 (NO.20 item of SAPS for r = 0.31, p = 0.0024, P1 item of PANSS for r = 0.27, p = 0.0074). The delusion-related network comprises the connections between the default mode network (DMN), cingulo-opercular network (CON), salience network (SN), subcortical, sensory-somatomotor network (SMN), and visual networks. We successfully established correlation models of individualized delusion based on the WM-related functional connectome and showed a strong correlation between delusion severity and connections within the DMN, CON, SMN, and subcortical network.

Aberrant brain dynamics in major depressive disorder during working memory task.

Working memory (WM) is a distributed and dynamic process, and WM deficits are recognized as one of the top-ranked endophenotype candidates for major depressive disorders (MDD). However, there is a lack of knowledge of brain temporal-spatial profile of WM deficits in MDD. We used the dynamical degree centrality (dDC) to investigate the whole-brain temporal-spatial profile in 40 MDD and 40 controls during an n-back task with 2 conditions (i.e., '0back' and '2back'). We explored the dDC temporal variability and clustered meta-stable states in 2 groups during different WM conditions. Pearson's correlation analysis was used to evaluate the relationship between the altered dynamics with clinical symptoms and WM performance. Compared with controls, under '2back vs. 0back' contrast, patients showed an elevated dDC variability in wide range of brain regions, including the middle frontal gyrus, orbital part of inferior frontal gyrus (IFGorb), hippocampus, and middle temporal gyrus. Furthermore, the increased dDC variability in the hippocampus and IFGorb correlated with worse WM performance. However, there were no significant group-related differences in the meta-stable states were observed. This study demonstrated the increased WM-related instability (i.e., the elevated dDC variability) was represented in MDD, and enhancing stability may help patients achieve better WM performance.

Effects of long-term antipsychotic medication on brain instability in first-episode schizophrenia patients: a resting-state fMRI study.

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms.

The neural compensation phenomenon in schizophrenia with mild attention deficits during working memory task.

BACKGROUND: Working memory (WM) and attention are essential cognitive processes, and their interplay is critical for efficient information processing. Schizophrenia often exhibits deficits in both WM and attention, contributing to function impairments. This study aims to investigate the neural mechanisms underlying the relationship between WM impairments and attention deficits in schizophrenia. METHODS: We assessed the functional-MRI scans of the 184 schizophrenias with different attention deficits (mild=133; severe=51) and 146 controls during an N-back WM task. We explored their whole-brain functional connectome profile by adopting the voxel-wise degree centrality (DC). Linear analysis was conducted to explore the associations among attention deficit severity, altered DC, and WM performance in patients. RESULTS: We observed that all patients showed decreased DC in the pre-supplementary area (pre-SMA), and posterior cerebellum compared to the controls, and schizophrenia patients with mild attention deficits showed decreased DC in the supramarginal gyrus, insula, and precuneus compared with the other 2 groups. DC values of the detected brain regions displayed U-shaped or inverted U-shaped curves, rather than a linear pattern, in response to increasing attention deficits. The linear analysis indicated that altered DC of the pre-SMA can modulate the relationship between attention deficits and WM performance. CONCLUSION: The U-shaped or inverted U-shaped pattern in response to increasing attention deficits may reflect a compensation mechanism in schizophrenia with mild attention deficits. This notion is also supported by the linear analysis that schizophrenia patients with mild attention deficits can improve their WM performance by increasing the DC value of the pre-SMA.

Modeling and experimental analysis of wire-driven continuum surgical robot.

A new configuration of continuum surgical robot is proposed, whose skeleton is composed of inner and outer layers. The outer layer is composed of miniature rotating modules connected in series and connected by orthogonal hinges, which can ensure the ability to resist unconventional torsion without losing the degree of freedom. The inner layer is a central support column with superelasticity. When bending, its superelasticity can make the overall configuration biased toward constant curvature bending, which is convenient for motion control and according to the new configuration, this paper establishes the kinematics model of the robot. Finally, the motion control experiment of the continuum robot is carried out. After the experiment, the average positioning error of the robot is 2.674 mm, and the average repetitive positioning error is 2.625 mm. Both are less than 2 % of the robot length, verifying the accuracy of the model.

Aberrant Brain Dynamics in Schizophrenia During Working Memory Task: Evidence From a Replication Functional MRI Study.

BACKGROUND AND HYPOTHESIS: The integration of information that typifies working memory (WM) operation requires a flexible, dynamic functional relationship among brain regions. In schizophrenia, though WM capacity is prominently impaired at higher loads, the mechanistic underpinnings are unclear. As a result, we lack convincing cognitive remediation of load-dependent deficits. We hypothesize that reduced WM capacity arises from a disruption in dynamic functional connectivity when patients face cognitive demands. STUDY DESIGN: We calculate the dynamic voxel-wise degree centrality (dDC) across the functional connectome in 142 patients with schizophrenia and 88 healthy controls (HCs) facing different WM loads during an n-back task. We tested associations of the altered variability in dDC and clinical symptoms and identified intermediate connectivity configurations (clustered states) across time during WM operation. These analyses were repeated in another independent dataset of 169 subjects (102 with schizophrenia). STUDY RESULTS: Compared with HCs, patients showed an increased dDC variability of supplementary motor area (SMA) for the "2back vs. 0back" contrast. This instability at the SMA seen in patients correlated with increased positive symptoms and followed a limited "U-shape" pattern at rest-condition and 2 loads. In the clustering analysis, patients showed reduced centrality in the SMA, superior temporal gyrus, and putamen. These results were replicated in a constrained search in the second independent dataset. CONCLUSIONS: Schizophrenia is characterized by a load-dependent reduction of stable centrality in SMA; this relates to the severity of positive symptoms, especially disorganized behaviour. Restoring SMA stability in the presence of cognitive demands may have a therapeutic effect in schizophrenia.

Load-dependent inverted U-shaped connectivity of the default mode network in schizophrenia during a working-memory task: evidence from a replication functional MRI study.

BACKGROUND: Working-memory deficit is associated with aberrant degree distribution of the brain connectome in schizophrenia. However, the brain neural mechanism underlying the degree redistribution pattern in schizophrenia is still uncertain. METHODS: We examined the functional degree distribution of the connectome in 81 patients with schizophrenia and 77 healthy controls across different working-memory loads during an n-back task. We tested the associations between altered degree distribution and clinical symptoms, and we conducted functional connectivity analyses to investigate the neural mechanism underlying altered degree distribution. We repeated these analyses in a second independent data set of 96 participants. In the second data set, we employed machine-learning analysis to study whether the degree distribution pattern of one data set could be used to discriminate between patients with schizophrenia and controls in the other data set. RESULTS: Patients with schizophrenia showed decreased centrality in the dorsal posterior cingulate cortex (dPCC) for the "2-back versus 0-back" contrast compared to healthy controls. The dPCC centrality pattern across all working-memory loads was an inverted U shape, with a left shift of this pattern in patients with schizophrenia. This reduced centrality was correlated with the severity of delusions and related to reduced functional connectivity between the dPCC and the dorsal precuneus. We replicated these results with the second data set, and the machine-learning analyses achieved an accuracy level of 71%. LIMITATIONS: We used a limited n-back paradigm that precluded the examination of higher working-memory loads. CONCLUSION: Schizophrenia is characterized by a load-dependent reduction of centrality in the dPCC, related to the severity of delusions. We suggest that restoring dPCC centrality in the presence of cognitive demands might have a therapeutic effect on persistent delusions in people with schizophrenia.

Pressure Transient Analysis for Hydraulically Fractured Wells with Changing Conductivity in Stratified Reservoirs: Case Study in Xinjiang Oilfield.

The oil development has been oriented toward deep-layer reservoirs and the commingling production and the separate-layer fracturing are important development methods. Currently, limited attention is given to the pressure transient analysis (PTA) of the fractured wells located in a stratified reservoir. Moreover, the proppant is very difficult to move inside the hydraulic fracture in the deep-layer reservoir, leading to the uneven fracture conductivity along the hydraulic fracture and increasing the complexity of PTA. To fill this gap, this work presented a fully analytical well test model for hydraulically fractured wells with changing fracture conductivity in stratified reservoirs, which is convenient to be used for interpreting the recorded pressure data from the oilfield due to its analytical nature. The establishment of this model is based on the trilinear flow model, Duhamel theorem, and pressure superposition principle. A systematic verification is conducted to ensure the validity of the proposed model. Furthermore, we offer a sensitivity analysis to investigate the effect of crucial parameters on pressure and pressure derivative, including the fracture extension, fracture conductivity, transmissibility factor, and storativity factor. Finally, a field case of a four-layer fractured well from Xinjiang Oilfield in Junggar Basin is interpreted to demonstrate the practicability of the presented model.

Association Between Wisdom and Psychotic-Like Experiences in the General Population: A Cross-Sectional Study.

Introduction: Wisdom has been empirically researched as a complex psychological characteristic that is associated with many mental health outcomes. However, its association with psychotic-like experiences (PLEs) remains unclear. This is the first work to assess wisdom, explore its association with PLEs, and test its moderating effect on the relation between the frequency of PLEs and their associated distress in the general population. Methods: From January 29th to February 5th, 2021, our online self-administered survey recruited 927 participants (ages 14 to 65) from thirteen Chinese provinces. Convenience sampling was employed. We measured wisdom with the 12-item three-dimensional wisdom scale (3D-WS-12) and PLEs with the 15-item positive subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Results: Using the cut-off value of 1.47 in the mean frequency score, we divided our participants into high-PLEs group (188, 22.1%) and low-PLEs group (663, 77.9%). Three-dimensional wisdom score was decreased in the high-PLEs group compared to the low-PLEs group (Kruskal-Wallis t = 59.9, p < 0.001). Wisdom was associated with less frequent PLEs (Spearman's rho = -0.21, p < 0.01) and lower distress related to PLEs (Spearman's rho = -0.28) in the high-PLEs group (all above p < 0.001), which were replicated in the low-PLEs group. Notably, wisdom significantly attenuated the distress associated with PLEs [coefficient = -0.018, Bootstrap 95% CI (-0.029, -0.008)], but only in the low-PLEs group. Conclusion: Our results implicated that wisdom could protect individuals from distressful subclinical psychotic symptoms and wiser individuals have better general mental health.

Changes of psychotic-like experiences and their association with anxiety/depression among young adolescents before COVID-19 and after the lockdown in China.

OBJECTIVE: Lockdown policies during COVID-19 pandemic have potential adverse psychological impacts on youth. However, little is known about their influence on the changes of psychotic-like experiences (PLEs) among adolescents, nor about the possible association between changes in PLEs and changes in anxiety/depression symptoms. We investigated these two questions through a longitudinal comparative study. METHODS: In total, 1825 adolescents were surveyed before COVID-19 and after the lockdown in China (T0, October 20th, 2019 and T1, May 18th, 2020). PLEs, anxiety, and depression were measured with paranoia, anxiety and depression subscales of the Mental Health Inventory of Middle school students (MMHI-60). Within-subjects Wilcoxon test, Spearman correlation test, and Kruskal-Wallis test were adopted. RESULTS: Significant increase in adolescent PLEs scores was observed after the lockdown (Wilcoxon's w = 9.302, p < 0.001). We also found positive correlation between changes of PLEs and changes of anxiety/depression (Spearman's rho = 0.59/0.53, both p < 0.001). Furthermore, four PLEs trajectories were identified based on the report of PLEs at two timepoints: 60.4% with no PLEs, 9.3% remitted PLEs, 16.7% new PLEs, and 13.6% persistent PLEs. Significant difference was found in changes of anxiety/depression among four groups (p < 0.001); notably, the group with new-onset PLEs had the greatest exacerbation in anxiety/depression symptoms (both p Bonferroni <0.001). CONCLUSIONS: This work is the first to identify increases in adolescent PLEs across the COVID-19 pandemic and suggested a close longitudinal association between PLEs and anxiety/depression. Our findings have implications for adolescent mental health crisis interventions during the pandemic.

Family functioning as a moderator in the relation between perceived stress and psychotic-like experiences among adolescents during COVID-19.

BACKGROUND: The COVID-19 pandemic has increased psychological stress among adolescents, and the relation between perceived stress (PS) and psychotic-like experiences (PLEs) has been well-established. However, little is known about the role of family functioning (FF) in this relation, especially when adolescents experienced the extended lockdown period with family members. METHODS: A total of 4807 adolescents completed this retrospective paper-and-pencil survey after school reopening between May 14th and June 6th, 2020 in Hunan Province, China. We measured PS with the Perceived stress scale (PSS-10), PLEs with the eight positive items from Community Assessment of Psychic Experiences (CAPE-8), and FF with the Family APGAR scale. We conducted subgroup analysis based on three FF levels (good, moderate, and poor) determined by previous studies. Finally, correlation and moderation analysis were performed to detect the effect of FF in the relation between PS and PLEs after adjusting for demographic variables. RESULTS: Adolescents with poor FF had higher levels of PS and higher prevalence of PLEs compared to those with good FF (both p < 0.001). FF was negatively associated with both PS (r = -0.34, p < 0.001) and PLEs (r = -0.29, p < 0.001). Higher FF significantly attenuated the effect of PS on PLEs after adjusting for sex and age (effect = -0.011, bootstrap 95% CI -0.018, -0.005). CONCLUSION: Our findings indicate that well-functioned family could protect against stress-induced PLEs among adolescents during this crisis. Thus family system could be an early interventional target for distressing psychotic-like experiences in youngsters.