Combinatorial Engineering of Escherichia coli for Enhancing 3-Fucosyllactose Production.

3-Fucosyllactose (3-FL) is an important fucosylated human milk oligosaccharide (HMO) with biological functions such as promoting immunity and brain development. Therefore, the construction of microbial cell factories is a promising approach to synthesizing 3-FL from renewable feedstocks. In this study, a combinatorial engineering strategy was used to achieve efficient de novo 3-FL production in Escherichia coli. α-1,3-Fucosyltransferase (futM2) from Bacteroides gallinaceum was introduced into E. coli and optimized to create a 3-FL-producing chassis strain. Subsequently, the 3-FL titer increased to 5.2 g/L by improving the utilization of the precursor lactose and down-regulating the endogenous competitive pathways. Furthermore, a synthetic membraneless organelle system based on intrinsically disordered proteins was designed to spatially regulate the pathway enzymes, producing 7.3 g/L 3-FL. The supply of the cofactors NADPH and GTP was also enhanced, after which the 3-FL titer of engineered strain E26 was improved to 8.2 g/L in a shake flask and 10.8 g/L in a 3 L fermenter. In this study, we developed a valuable approach for constructing an efficient 3-FL-producing cell factory and provided a versatile workflow for other chassis cells and HMOs.

Efficacy and safety of electroacupuncture for benign prostatic hyperplasia: A systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the efficacy and safety of electroacupuncture (EA) in the treatment of benign prostatic hyperplasia. METHODS: Seven databases were searched from the inception of each database to March 31, 2023, including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, Wanfang, and China Biology Medicine. The modified Jadad scale was used to assess literature quality, and literature inclusion and exclusion were conducted in strict accordance with the criteria of a score of ≥4. The risk of bias was evaluated using the Cochrane risk of bias tool. The pooled effect size of the binary data was measured by odds ratio (OR) and 95% confidence interval (CI), and the pooled effect size of the continuous data was presented as weighted mean difference (WMD) and 95% CI. If I² was larger than 50%, a random effects model was adopted, and otherwise, a fixed effects model was used. Additionally, publication bias assessment and sensitivity analysis were conducted. RESULTS: A total of 325 records were retrieved, and finally 9 randomized controlled trial studies were included, involving 1045 patients. Meta-analysis revealed that the EA group had better improvement than the control group in terms of clinical effective rate (odds ratio = 3.92, 95% CI = 2.38 to 6.47, I²â€…= 0%, P < .001), International Prostate Symptom Score (WMD = -4.99, 95% CI = -6.15 to -3.84, I²â€…= 76.9%, P < .001), maximum urinary flow rate (WMD = -4.99, 95% CI = -6.15 to -3.84, I²â€…= 87.4%, P < .001), and post-void residual volume (WMD = -17.12, 95% CI = -29.49 to -4.75, I²â€…= 89.1%, P < .01). There was no statistical significance in prostate volume and adverse events between the EA group and the control group (P > .05). CONCLUSION: EA is effective in the treatment of benign prostatic hyperplasia with acceptable overall safety.

Acupuncture for post-stroke spasticity: An overview of systematic reviews.

BACKGROUND: Post-stroke spasticity (PSS) is the most common complication of stroke. Acupuncture is widely used in clinical practice for the treatment of PSS, and is therefore considered a common complementary treatment. Several systematic reviews (SRs) and meta-analyses (MAs) have demonstrated the efficacy and safety of acupuncture in the treatment of PSS; however, the quality of evidence of these studies has not been adequately assessed. OBJECTIVE: To evaluate and summarize the SRs/MAs and inform future research and clinical practice on the efficacy and safety of acupuncture for PSS. DATA SOURCES AND EXTRACION: The following databases were searched from their dates of inception to March 26, 2023: PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, SinoMed, and Chinese Science and Technology Periodical Database (VIP), and grey literature were manually searched. Two reviewers independently completed literature retrieval, screening, and data extraction. REVIEW APPRAISAL: Systematic evaluation tools to Assess Systematic Reviews (AMSTAR) 2, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020 Checklist), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to systematically evaluate the methodological, reporting, and evidence quality of the SRs/MAs. RESULTS: Overall, 226 papers were examined, and after careful consideration, 10 SRs/MAs were deemed eligible for inclusion. The AMSTAR 2 assessment revealed that one SR/MA had medium, one study had low, and the remaining eight studies had critically low methodological qualities. Additionally, four SRs/MAs completed more than 60 % of the PRISMA 2020 checklist. The GRADE system indicated that six outcomes were medium, 26 outcomes were low, and 24 outcomes were critically low. CONCLUSION: Based on the evidence, acupuncture may be a promising complementary treatment to improve post-stroke spasticity and quality of life. Further high-quality RCTs are needed in future studies to support the broader application of acupuncture for the treatment of PSS.

Functional brain network alterations in the co-occurrence of autism spectrum disorder and attention deficit hyperactivity disorder.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two highly prevalent and commonly co-occurring neurodevelopmental disorders. The neural mechanisms underpinning the comorbidity of ASD and ADHD (ASD + ADHD) remain unclear. We focused on the topological organization and functional connectivity of brain networks in ASD + ADHD patients versus ASD patients without ADHD (ASD-only). Resting-state functional magnetic resonance imaging (rs-fMRI) data from 114 ASD and 161 typically developing (TD) individuals were obtained from the Autism Brain Imaging Data Exchange II. The ASD patients comprised 40 ASD + ADHD and 74 ASD-only individuals. We constructed functional brain networks for each group and performed graph-theory and network-based statistic (NBS) analyses. Group differences between ASD + ADHD and ASD-only were analyzed at three levels: nodal, global, and connectivity. At the nodal level, ASD + ADHD exhibited topological disorganization in the temporal and occipital regions, compared with ASD-only. At the global level, ASD + ADHD and ASD-only displayed no significant differences. At the connectivity level, the NBS analysis revealed that ASD + ADHD showed enhanced functional connectivity between the prefrontal and frontoparietal regions, as well as between the orbitofrontal and occipital regions, compared with ASD-only. The hippocampus was the shared region in aberrant functional connectivity patterns in ASD + ADHD and ASD-only compared with TD. These findings suggests that ASD + ADHD displays altered topology and functional connectivity in the brain regions that undertake social cognition, language processing, and sensory processing.

Corticospinal tract: a new hope for the treatment of post-stroke spasticity.

Stroke is the third leading cause of death and disability worldwide. Post-stroke spasticity (PSS) is the most common complication of stroke but represents only one of the many manifestations of upper motor neuron syndrome. As an upper motor neuron, the corticospinal tract (CST) is the only direct descending motor pathway that innervates the spinal motor neurons and is closely related to the recovery of limb function in patients with PSS. Therefore, promoting axonal remodeling in the CST may help identify new therapeutic strategies for PSS. In this review, we outline the pathological mechanisms of PSS, specifically their relationship with CST, and therapeutic strategies for axonal regeneration of the CST after stroke. We found it to be closely associated with astroglial scarring produced by astrocyte activation and its secretion of neurotrophic factors, mainly after the onset of cerebral ischemia. We hope that this review offers insight into the relationship between CST and PSS and provides a basis for further studies.

Altered functional brain network patterns in patients with migraine without aura after transcutaneous auricular vagus nerve stimulation.

Transcutaneous auricular vagus nerve stimulation (taVNS) shows excellent effects on relieving clinical symptoms in migraine patients. Nevertheless, the neurological mechanisms of taVNS for migraineurs remain unclear. In recent years, voxel-wise degree centrality (DC) and functional connectivity (FC) methods were extensively utilized for exploring alterations in patterns of FC in the resting-state brain. In the present study, thirty-five migraine patients without aura and thirty-eight healthy controls (HCs) were recruited for magnetic resonance imaging scans. Firstly, this study used voxel-wise DC analysis to explore brain regions where abnormalities were present in migraine patients. Secondly, for elucidating neurological mechanisms underlying taVNS in migraine, seed-based resting-state functional connectivity analysis was employed to the taVNS treatment group. Finally, correlation analysis was performed to explore the relationship between alterations in neurological mechanisms and clinical symptoms. Our findings indicated that migraineurs have lower DC values in the inferior temporal gyrus (ITG) and paracentral lobule than in healthy controls (HCs). In addition, migraineurs have higher DC values in the cerebellar lobule VIII and the fusiform gyrus than HCs. Moreover, after taVNS treatment (post-taVNS), patients displayed increased FC between the ITG with the inferior parietal lobule (IPL), orbitofrontal gyrus, angular gyrus, and posterior cingulate gyrus than before taVNS treatment (pre-taVNS). Besides, the post-taVNS patients showed decreased FC between the cerebellar lobule VIII with the supplementary motor area and postcentral gyrus compared with the pre-taVNS patients. The changed FC of ITG-IPL was significantly related to changes in headache intensity. Our study suggested that migraine patients without aura have altered brain connectivity patterns in several hub regions involving multisensory integration, pain perception, and cognitive function. More importantly, taVNS modulated the default mode network and the vestibular cortical network related to the dysfunctions in migraineurs. This paper provides a new perspective on the potential neurological mechanisms and therapeutic targets of taVNS for treating migraine.

Bioequivalence of Celecoxib Capsules in Chinese Healthy Volunteers.

Celecoxib is a sulfanilamide nonsteroidal anti-inflammatory drug that can selectively inhibit cyclooxygenase-2 to inhibit prostaglandin production, achieving anti-inflammatory and analgesic effects. This study investigated the pharmacokinetics, safety, and bioequivalence of a single oral dose of celecoxib capsule (the test or reference preparation) in healthy volunteers under fasting and fed conditions. A single-center, randomized, open, single-dose, double-cycle crossover self-control design was conducted: 40 healthy volunteers were enrolled in the fasting and fed groups, respectively. A completely randomized method was used, with one group taking the test celecoxib preparation (T) and the other taking the reference celecoxib preparation (R). During the administration period, the safety of the drug was evaluated simultaneously, and venous blood was collected at the corresponding time points. The concentration of celecoxib in plasma was measured by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were logarithmically converted and analyzed for variance. The 90% confidence interval for the bioavailability of the T compared to the R was calculated using maximum drug plasma concentration, area under the plasma concentration-time curve from time zero to the last quantifiable concentration point, and area under the plasma concentration-time curve from time zero to infinity for a single oral dose in volunteers, and the data obtained were all between 80% and 125%, indicating that the T and R have bioequivalence and good safety during fasting and fed administration.

Comparing the blood oxygen level-dependent fluctuation power of benign and malignant musculoskeletal tumors using functional magnetic resonance imaging.

Purpose: The aim of this study is to compare the blood oxygen level-dependent (BOLD) fluctuation power in 96 frequency points ranging from 0 to 0.25 Hz between benign and malignant musculoskeletal (MSK) tumors via power spectrum analyses using functional magnetic resonance imaging (fMRI). Materials and methods: BOLD-fMRI and T1-weighted imaging (T1WI) of 92 patients with benign or malignant MSK tumors were acquired by 1.5-T magnetic resonance scanner. For each patient, the tumor-related BOLD time series were extracted, and then, the power spectrum of BOLD time series was calculated and was then divided into 96 frequency points. A two-sample t-test was used to assess whether there was a significant difference in the powers (the "power" is the square of the BOLD fluctuation amplitude with arbitrary unit) of each frequency point between benign and malignant MSK tumors. The receiver operator characteristic (ROC) analysis was used to assess the diagnostic capability of distinguishing between benign and malignant MSK tumors. Results: The result of the two-sample t-test showed that there was significant difference in the power between benign and malignant MSK tumor at frequency points of 58 (0.1508 Hz, P = 0.036), 59 (0.1534 Hz, P = 0.032), and 95 (0.247 Hz, P = 0.014), respectively. The ROC analysis of mean power of three frequency points showed that the area of under curve is 0.706 (P = 0.009), and the cutoff value is 0.73130. If the power of the tumor greater than or equal to 0.73130 is considered the possibility of benign tumor, then the diagnostic sensitivity and specificity values are 83% and 59%, respectively. The post hoc analysis showed that the merged power of 0.1508 and 0.1534 Hz in benign MSK tumors was significantly higher than that in malignant ones (P = 0.014). The ROC analysis showed that, if the benign MSK tumor was diagnosed with the power greater than or equal to the cutoff value of 1.41241, then the sensitivity and specificity were 67% and 68%, respectively. Conclusion: The mean power of three frequency points at 0.1508, 0.1534, and 0.247 Hz may potentially be a biomarker to differentiate benign from malignant MSK tumors. By combining the power of 0.1508 and 0.1534 Hz, we could better detect the difference between benign and malignant MSK tumors with higher specificity.

Uncovering neural distinctions and commodities between two creativity subsets: A meta-analysis of fMRI studies in divergent thinking and insight using activation likelihood estimation.

The dual-process theory that two different systems of thought coexist in creative thinking has attracted considerable attention. In the field of creative thinking, divergent thinking (DT) is the ability to produce multiple solutions to open-ended problems in a short time. It is mainly considered an associative and fast process. Meanwhile, insight, the new and unexpected comprehension of close-ended problems, is frequently marked as a deliberate and time-consuming thinking process requiring concentrated effort. Previous research has been dedicated to revealing their separate neural mechanisms, while few studies have compared their differences and similarities at the brain level. Therefore, the current study applied Activation Likelihood Estimation to decipher common and distinctive neural pathways that potentially underlie DT and insight. We selected 27 DT studies and 30 insight studies for retrospective meta-analyses. Initially, two single analyses with follow-up contrast and conjunction analyses were performed. The single analyses showed that DT mainly involved the inferior parietal lobe (IPL), cuneus, and middle frontal gyrus (MFG), while the precentral gyrus, inferior frontal gyrus (IFG), parahippocampal gyrus (PG), amygdala (AMG), and superior parietal lobe were engaged in insight. Compared to insight, DT mainly led to greater activation in the IPL, the crucial part of the default mode network. However, insight caused more significant activation in regions related to executive control functions and emotional responses, such as the IFG, MFG, PG, and AMG. Notably, the conjunction analysis detected no overlapped areas between DT and insight. These neural findings implicate that various neurocognitive circuits may support DT and insight.

The Role of Qi-Stagnation Constitution and Emotion Regulation in the Association Between Childhood Maltreatment and Depression in Chinese College Students.

Background: Childhood maltreatment is known as a significant risk factor for later depression. However, there remains a lack of understanding about the mechanisms through which childhood maltreatment confers risk for depression. This study explores how Qi-stagnation constitution (QSC) and emotion regulation affect the link between childhood maltreatment and depressive symptoms in Chinese college students. Methods: We recruited 2,108 college students aged 18-25 years between November 2020 and December 2021. Participants were required to complete four self-report questionnaires, including the Childhood Trauma Questionnaire-Short Form (CTQ-SF), Qi-Stagnation Constitution (QSC) subscale of the simplified Chinese Medicine Constitution Questionnaire, Difficulties in Emotion Regulation Scale (DERS), and the Beck Depression Inventory-II (BDI-II). Moderated mediation analyses were conducted. Results: There was a positive correlation between childhood maltreatment and QSC, while the QSC partially mediated the effect of childhood maltreatment on depressive scores in college students. In addition, emotion dysregulation moderated the association between QSC and depressive scores. Conclusion: These results enhance understanding of key factors influencing the link between childhood maltreatment and depressive symptoms among college students by combining the theory of TCM constitution with psychological processes. The development of strategies to prevent biased Qi-stagnation constitution and emotion dysregulation may help to improve college students' mental health and strengthen the resilience of individuals to depression.

Multimodal MRI reveals alterations of the anterior insula and posterior cingulate cortex in bipolar II disorders: A surface-based approach.

BACKGROUND: Bipolar disorder (BD) is a mental disorder with severe implications for those affected and their families. Previous studies detected brain structural and functional alterations in BD patients. However, very few studies conducted a multimodal MRI fusion analysis, and little is known about the role of common anomalies in the connectivity of BD. METHODS: We collected sMRI, rs-fMRI, and DTI data from 56 patients with unmedicated BD-II depression and 72 age-, sex- and handedness-matched healthy controls. We applied data-driven approaches to analyze multimodal MRI data and detected brain areas with significant group differences in cortical thickness (CT), amplitude of low frequency fluctuations (ALFF), and fractional anisotropy (FA) of the superficial white matter. We observed the common abnormal areas and took these areas as seeds to analyze the resting-state functional connectivity (RSFC) patterns in BD patients by overlapping these abnormal areas. RESULTS: The BD patients showed two common abnormal areas: (1) the left anterior insula (AI) with abnormal CT and FA, and (2) the left posterior cingulate cortex (PCC) with abnormal CT and ALFF. Seed-based analyses showed RSFC between the left AI and left occipital sensory cortex, the left AI and left superior and inferior parietal cortex, and the left PCC and right medial prefrontal cortex were uniformly lower in the BD patients than controls. Correlation analyses showed negative correction between AI's FA and disease episodes and between AI's FA and disease duration in depressed BD-II patients. CONCLUSIONS: We observed abnormal brain structural and functional properties in the left AI and left PCC in BD patients. The abnormal RSFC patterns may suggest sensory and cognitive dysfunction in BD.

Rational preparation and application of a mRNA delivery system with cytidinyl/cationic lipid.

The messenger RNA (mRNA)-based therapy, especially mRNA vaccines, has shown its superiorities in versatile design, rapid development and scale production, since the outbreak of coronavirus disease 2019 (COVID-19). Although the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines had been approved for application, unexpected adverse events were reported to be most likely associated with the mRNA delivery systems. Thus, the development of mRNA delivery system with good efficacy and safety remains a challenge. Here, for the first time, we report that the neutral cytidinyl lipid, 2-(4-amino-2-oxopyrimidin-1-yl)-N-(2,3-dioleoyl-oxypropyl) acetamide (DNCA), and the cationic lipid, dioleoyl-3,3'-disulfanediylbis-[2-(2,6-diaminohexanamido)] propanoate (CLD), could encapsulate and deliver the COVID-19 mRNA-1096 into the cytoplasm to induce robust adaptive immune response. In the formulation, the molar ratio of DNCA/CLD to a single nucleotide of COVID-19 mRNA-1096 was about 0.9: 0.5: 1 (the N/P ratio was about 7: 1). The DNCA/CLD-mRNA-1096 lipoplexes were rationally prepared by the combination of the lipids DNCA/CLD with the aqueous mRNA solution under mild sonication to stimulate multiple interactions, including H-bonding, π-stacking and electrostatic force between the lipids and the mRNA. After intramuscular applications of the DNCA/CLD-mRNA-1096 lipoplexes, robust neutralizing antibodies and long-lived Th1-biased SARS-CoV-2-specific cell immunity were detected in the immunized mice, thus suggesting the DNCA/CLD a promising mRNA delivery system. Moreover, our study might also inspire better ideas for developing mRNA delivery systems.

Time-delay structure predicts clinical scores for patients with disorders of consciousness using resting-state fMRI.

BACKGROUND: The detection of intrinsic brain activity (iBA) could assist clinical assessment for disorder of consciousness (DOC) patients. Previous studies have revealed the altered iBA in thalamocortical, frontoparietal, and default mode network in DOC patients using functional connectivity (FC) analysis. However, due to the assumption of synchronized iBA in FC, these studied may be inadequate for understanding the effect of severe brain injury on the temporal organization of iBA and the relationship between temporal organization and clinical feature in DOC patients. Recently, the time delay estimation (TDE) and probabilistic flow estimation (PFE) were proposed to analyze temporal organization, which could provide propagation structure and propagation probability at whole-brain level. METHODS: We applied voxel-wise TDE and PFE to assess propagation structure and propagation probability for the DOC patients and then applied the connectome-based predictive modeling (CPM) to predict clinical scores for patients based on the ROI-wise TDE and PFE. RESULTS: We found that: 1) the DOC patients showed abnormal voxel-wise time delay (TD) and probabilistic flow (PF) in the precentral gyrus, precuneus, middle cingulate cortex, and postcentral gyrus, 2) the range of TD value in the patients was shorter than that in the controls, and 3) the ROI-wise TD had a better predictive performance for clinical scores of the patients compared with that based on ROI-wise PF. CONCLUSION: Our findings may suggest that the propagation structure of iBA could be used to predict clinical scores in DOC patients.

Connectome-based models can predict processing speed in older adults.

Decrement in processing speed (PS) is a primary cognitive morbidity in clinical populations and could significantly influence other cognitive functions, such as attention and memory. Verifying the usefulness of connectome-based models for predicting neurocognitive abilities has significant translational implications on clinical and aging research. In this study, we verified that resting-state functional connectivity could be used to predict PS in 99 older adults by using connectome-based predictive modeling (CPM). We identified two distinct connectome patterns across the whole brain: the fast-PS and slow-PS networks. Relative to the slow-PS network, the fast-PS network showed more within-network connectivity in the motor and visual networks and less between-network connectivity in the motor-visual, motor-subcortical/cerebellum and motor-frontoparietal networks. We further verified that the connectivity patterns for prediction of PS were also useful for predicting attention and memory in the same sample. To test the generalizability and specificity of the connectome-based predictive models, we applied these two connectome models to an independent sample of three age groups (101 younger adults, 103 middle-aged adults and 91 older adults) and confirmed these models could specifically be generalized to predict PS of the older adults, but not the younger and middle-aged adults. Taking all the findings together, the identified connectome-based predictive models are strong for predicting PS in older adults. The application of CPM to predict neurocognitive abilities can complement conventional neurocognitive assessments, bring significant clinical benefits to patient management and aid the clinical diagnoses, prognoses and management of people undergoing the aging process.

Dynamic Properties of Human Default Mode Network in Eyes-Closed and Eyes-Open.

The default mode network (DMN) reflects spontaneous activity in the resting human brain. Previous studies examined the difference in static functional connectivity (sFC) of the DMN between eyes-closed (EC) and eyes-open (EO) using the resting-state functional magnetic resonance imaging (rs-fMRI) data. However, it remains unclear about the difference in dynamic FC (dFC) of the DMN between EC and EO. To this end, we acquired rs-fMRI data from 19 subjects in two different statues (EC and EO) and selected a seed region-of-interest (ROI) at the posterior cingulate cortex (PCC) to generate the sFC map. We identified the DMN consisting of ten clusters that were significantly correlated with the PCC. By using a sliding-window approach, we analyzed the dFC of the DMN. Then, the Newman's modularity algorithm was applied to identify dFC states based on nodal total connectivity strength in each sliding-window. In addition, graph-theory based network analysis was applied to detect dynamic topological properties of the DMN. We identified three group-level dFC states (State1, 2 and 3) that reflects the strength of dFC within the DMN between EC and EO in different time. The following results were reached: (1) no significant difference in sFC between EC and EO, (2) dFC was lower in State2 but higher in State3 in EC than in EO, (3) lower clustering coefficient, local efficiency, and global efficiency, but higher characteristic path length in State2 in EC than in EO, and (4) lower nodal strength in the precuneus (PCUN), PCC, angular gyrus (ANG), middle temporal gyrus (MTG) and medial prefrontal cortex (MPFC) in State3 in EC. These results suggested different resting statuses, EC and EO, may induce different time-varying neural activity in the DMN.

Open eyes and closed eyes elicit different temporal properties of brain functional networks.

The eyes are our windows to the brain. There are differences in brain activity between people who have their eyes closed (EC) and eyes open (EO). Previous studies focused on differences in brain functional properties between these eyes conditions based on an assumption that brain activity is a static phenomenon. However, the dynamic nature of the brain activity in different eyes conditions is still unclear. In this study, we collected resting-state fMRI data from 21 healthy subjects in the EC and EO conditions. Using a sliding time window approach and a k-means clustering algorithm, we calculated the temporal properties of dynamic functional connectivity (dFC) states in the eyes conditions. We also used graph theory to estimate the dynamic topological properties of functional networks in the two conditions. We detected two dFC states, a hyper-connected State 1 and a hypo-connected State 2. We showed the following results: (i) subjects in the EC condition stayed longer in the hyper-connected State 1 than those in the EO; (ii) subjects in the EO condition stayed longer in the hypo-connected State 2 than those in the EC; and (iii) the dFC state transformed into the other state more frequently during EC than during EO. We also found the variance of the characteristic path length was higher during EC than during EO in the hyper-connected State 1. These results indicate that brain activity may be more active and unstable during EC than during EO. Our findings may provide insights into the dynamic nature of the resting-state brain and could be a useful reference for future rs-fMRI studies.

Shared and specific functional connectivity alterations in unmedicated bipolar and major depressive disorders based on the triple-network model.

Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) in clinical practice, especially during depressive episodes. A unifying triple-network model, involving the default mode network (DMN), central executive network (CEN) and salience network (SN), has been proposed to explain the neural physiopathology of psychiatric and neurological disorders. Although several studies revealed shared and specific alterations between BD and MDD in key regions of DMN, CEN, and SN, and a few studies used different measures to detect detailed alterations in the triple networks in BD and MDD, their shared and specific patterns of altered functional connectivity (FC) in the triple networks has remained unclear. In this study, we acquired resting-state fMRI (R-fMRI) data from 38 unmedicated BD and 35 unmedicated MDD patients during depressive episodes along with 47 healthy controls. We first determined the spatially independent components of the DMN, SN, and CEN by using independent component analysis (ICA); then we estimated the inter-ROI and inter-network FC for each group. By comparing the differences between the three groups, we obtained the following results: (1) both the BD and MDD patients showed shared weaker intra-network FC in the left mPFC and right precuneus within the DMN as well as weaker inter-ROI FC between the left AI and right AI compared with the healthy controls; (2) the BD had weaker while the MDD had stronger intra-network FC in the right dlPFC within the rCEN as well as stronger inter-ROI FC between the right dlPFC and right ANG compared with the healthy controls; (3) the BD showed specific, stronger inter-ROI FC between the left PPC and right AI as well as stronger inter-network FC between the lCEN and SN compared with either the MDD or the control group. Our findings provide new information for understanding the neural physiopathology and clinical symptoms of depressed BD and MDD patients.

Abnormal dynamic functional network connectivity in unmedicated bipolar and major depressive disorders based on the triple-network model.

BACKGROUND: Previous studies have analyzed brain functional connectivity to reveal the neural physiopathology of bipolar disorder (BD) and major depressive disorder (MDD) based on the triple-network model [involving the salience network, default mode network (DMN), and central executive network (CEN)]. However, most studies assumed that the brain intrinsic fluctuations throughout the entire scan are static. Thus, we aimed to reveal the dynamic functional network connectivity (dFNC) in the triple networks of BD and MDD. METHODS: We collected resting state fMRI data from 51 unmedicated depressed BD II patients, 51 unmedicated depressed MDD patients, and 52 healthy controls. We analyzed the dFNC by using an independent component analysis, sliding window correlation and k-means clustering, and used the parameters of dFNC state properties and dFNC variability for group comparisons. RESULTS: The dFNC within the triple networks could be clustered into four configuration states, three of them showing dense connections (States 1, 2, and 4) and the other one showing sparse connections (State 3). Both BD and MDD patients spent more time in State 3 and showed decreased dFNC variability between posterior DMN and right CEN (rCEN) compared with controls. The MDD patients showed specific decreased dFNC variability between anterior DMN and rCEN compared with controls. CONCLUSIONS: This study revealed more common but less specific dFNC alterations within the triple networks in unmedicated depressed BD II and MDD patients, which indicated their decreased information processing and communication ability and may help us to understand their abnormal affective and cognitive functions clinically.

Common and specific altered amplitude of low-frequency fluctuations in Parkinson's disease patients with and without freezing of gait in different frequency bands.

Freezing of gait (FOG), a disabling symptom of Parkinson's disease (PD), severely affects PD patients' life quality. Previous studies found neuropathologies in functional connectivity related to FOG, but few studies detected abnormal regional activities related to FOG in PD patients. In the present study, we analyzed the amplitude of low-frequency fluctuations (ALFF) to detect brain regions showing abnormal activity in PD patients with FOG (PD-with-FOG) and without FOG (PD-without-FOG). As different frequencies of neural oscillations in brain may reflect distinct brain functional and physiological properties, we conducted this study in three frequency bands, slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and classical frequency band (0.01-0.08 Hz). We acquired rs-fMRI data from 18 PD-with-FOG patients, 18 PD-without-FOG patients, and 17 healthy controls, then calculated voxel-wise ALFF across the whole brain and compared ALFF among the three groups in each frequency band. We found: (1) in slow-5, both PD-with-FOG and PD-without-FOG patients showed lower ALFF in the bilateral putamen compared to healthy controls, (2) in slow-4, PD-with-FOG patients showed higher ALFF in left inferior temporal gyrus (ITG) and lower ALFF in right middle frontal gyrus (MFG) compared to either PD-without-FOG patients or healthy controls, (3) in classical frequency band, PD-with-FOG patients also showed higher ALFF in ITG compared to either PD-without-FOG patients or healthy controls. Furthermore, we found that ALFF in MFG and ITG in slow-4 provided the highest classification accuracy (96.7%) in distinguishing PD-with-FOG from PD-without-FOG patients by using a stepwise multivariate pattern analysis. Our findings indicated frequency-specific regional spontaneous neural activity related to FOG, which may help to elucidate the pathogenesis of FOG.

Abnormalities of intrinsic regional brain activity in first-episode and chronic schizophrenia: a meta-analysis of resting-state functional MRI

Background: Resting-state functional MRI (fMRI) studies have provided much evidence for abnormal intrinsic brain activity in schizophrenia, but results have been inconsistent. Methods: We conducted a meta-analysis of whole-brain, resting-state fMRI studies that explored differences in amplitude of low-frequency fluctuation (ALFF) between people with schizophrenia (including first episode and chronic) and healthy controls. Results: A systematic literature search identified 24 studies comparing a total of 1249 people with schizophrenia and 1179 healthy controls. Overall, patients with schizophrenia displayed decreased ALFF in the bilateral postcentral gyrus, bilateral precuneus, left inferior parietal gyri and right occipital lobe, and increased ALFF in the right putamen, right inferior frontal gyrus, left inferior temporal gyrus and right anterior cingulate cortex. In the subgroup analysis, patients with first-episode schizophrenia demonstrated decreased ALFF in the bilateral inferior parietal gyri, right precuneus and left medial prefrontal cortex, and increased ALFF in the bilateral putamen and bilateral occipital gyrus. Patients with chronic schizophrenia showed decreased ALFF in the bilateral postcentral gyrus, left precuneus and right occipital gyrus, and increased ALFF in the bilateral inferior frontal gyri, bilateral superior frontal gyrus, left amygdala, left inferior temporal gyrus, right anterior cingulate cortex and left insula. Limitations: The small sample size of our subgroup analysis, predominantly Asian samples, processing steps and publication bias could have limited the accuracy of the results. Conclusion: Our comprehensive meta-analysis suggests that findings of aberrant regional intrinsic brain activity during the initial stages of schizophrenia, and much more widespread damage with the progression of disease, may contribute to our understanding of the progressive pathophysiology of schizophrenia.