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The article summarizes the relevant factors to the therapeutic effect of moxibustion on knee osteoarthritis, including the origin and storage time of moxa leaves, the time of moxibustion, the numbers of moxa cone, and the temperature when moxibustion is operated. Artemisia mugwort in Qichun county stored for over 3 years is the best regarding its property； and it is recommended for about 40 min in suspended moxibustion； and the heat-sensitive moxibustion is determined when the sensation of moxibustion disappears； and in terms of moxibustion techniques and the numbers of moxa cone, two moxa cones are optimal in warm needling, but the highly applicable duration of moxibustion needs to be confirmed through more high-quality studies. There are few studies on the other influencing factors, such as the specific operation of suspended moxibustion, the angle of knee flexion, treatment sequence, light and smoking factors, moxibustion method and disease staging and type； and the studies are limited in the comparison in terms of the middle-term and long-term efficacy, the comparison of the efficacy among different syndromes of traditional Chinese medicine in patients and the comparison among various frequencies and sessions of treatment. In future, more high-quality clinical trials should be designed to complete the evidence-based regimens and optimize clinical operations.

Abnormal resting-state effective connectivity in large-scale networks among obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic mental illness characterized by abnormal functional connectivity among distributed brain regions. Previous studies have primarily focused on undirected functional connectivity and rarely reported from network perspective. METHODS: To better understand between or within-network connectivities of OCD, effective connectivity (EC) of a large-scale network is assessed by spectral dynamic causal modeling with eight key regions of interests from default mode (DMN), salience (SN), frontoparietal (FPN) and cerebellum networks, based on large sample size including 100 OCD patients and 120 healthy controls (HCs). Parametric empirical Bayes (PEB) framework was used to identify the difference between the two groups. We further analyzed the relationship between connections and Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: OCD and HCs shared some similarities of inter- and intra-network patterns in the resting state. Relative to HCs, patients showed increased ECs from left anterior insula (LAI) to medial prefrontal cortex, right anterior insula (RAI) to left dorsolateral prefrontal cortex (L-DLPFC), right dorsolateral prefrontal cortex (R-DLPFC) to cerebellum anterior lobe (CA), CA to posterior cingulate cortex (PCC) and to anterior cingulate cortex (ACC). Moreover, weaker from LAI to L-DLPFC, RAI to ACC, and the self-connection of R-DLPFC. Connections from ACC to CA and from L-DLPFC to PCC were positively correlated with compulsion and obsession scores (r = 0.209, p = 0.037; r = 0.199, p = 0.047, uncorrected). CONCLUSIONS: Our study revealed dysregulation among DMN, SN, FPN, and cerebellum in OCD, emphasizing the role of these four networks in achieving top-down control for goal-directed behavior. There existed a top-down disruption among these networks, constituting the pathophysiological and clinical basis.

Gray matter morphological abnormities are constrained by normal structural covariance network in OCD.

A growing body of evidences reveal that abnormal gray matter morphology is constrained by normal brain network architecture in neurodegenerative and psychiatric disorders. However, whether this finding holds true in obsessive-compulsive disorder (OCD) remains unknown. In the current study, we aimed to investigate the association between gray matter morphological abnormities and normal structural covariance network architecture in OCD. First, gray matter morphological abnormities were obtained between 98 medicine-naive and first-episode patients with OCD and 130 healthy controls (HCs). Then, putative disease epicenters whose structural connectome profiles in HCs most resembled the morphological differences pattern were identified using a backfoward stepwise regression analysis. A set of brain regions were identified as putative disease epicenters whose structural connectome architecture significantly explained 59.94% variance of morphological abnormalities. These disease epicenters comprised brain regions implicated in high-order cognitive functions and sensory/motor processing. Other brain regions with stronger structural connections to disease epicenters exhibited greater vulnerability to disease. Together, these results suggest that gray matter abnormities are constrained by structural connectome and provide new insights into the possible pathological progression in OCD.

Decreased intrinsic neural timescales in obsessive compulsive disorder and two distinct subtypes revealed by heterogeneity through discriminative analysis.

BACKGROUND: OCD is featured as the destruction of information storage and processing. The cognition of neurobiological and clinical heterogeneity is in suspense and poorly studied. METHODS: Ninety-nine patients and matched HCs(n = 104) were recruited and underwent resting-state functional MRI scans. We applied INT to evaluate altered local neural dynamics representing the ability of information integration. Moreover, considering OCD was a highly heterogeneous disorder, we investigated putative OCD subtypes from INT using a novel semi-supervised machine learning, named HYDRA. RESULTS: Compared with HCs, patients with OCD showed decreased INTs in extensive brain regions, including bilateral cerebellum and precuneus, STG/MTG and PCC, hippocampus in DMN; right IFG/MFG/SFG, SPL and bilateral angular gyrus in CEN and insula, SMA in SN. Moreover, many other regions involved in visual processing also had disrupted dynamics of local neural organization, consisting of bilateral CUN, LING and fusiform gyrus and occipital lobe. HYDRA divided patients into two distinct neuroanatomical subtypes from INT. Subtype 1 showed decreased INTs in distributed networks, while subtype 2 presented increased in several common regions which were also found to be decreased in subtype 1, such as STG, IPL, postcentral gyrus and left insula, supramarginal gyrus. CONCLUSION: This study showed distinct abnormalities from the perspective of dynamics of local neural organization in OCD. Such alteration and dimensional approach may provide a new insight into the prior traditional cognition of this disorder and to some extent do favor of more precise diagnosis and treatment response in the future.

Abnormal voxel-mirrored homotopic connectivity in first-episode, drug-naïve patients with obsessive-compulsive disorder.

Prior studies suggest that obsessive-compulsive disorder (OCD) can cause both anatomical and functional variations in the brain, but to date, altered functional synchronization between two functional hemispheres remains unclear in OCD patients. Voxel-mirrored homotopic connectivity (VMHC) is defined as the temporal correlation of spontaneous low-frequency blood oxygenation level-dependent signal fluctuations across mirror regions of hemisphere revealing the homotopic connectivity between each voxel in one hemisphere and its mirrored counterpart in the contralateral hemisphere. To investigate the alterations of brain regional function and VMHC in patients with OCD, the current study enrolled 103 OCD patients and 118 healthy controls, undergoing resting-state functional magnetic resonance imaging. Compared to healthy controls (HCs), patients had decreased VMHC in bilateral cerebellum, lingual and fusiform gyrus; bilateral paracentral lobule, pre and postcentral gyrus; and bilateral superior and middle temporal gyrus, putamen and bilateral precuneus without global signal regression. And we found mostly similar results after regressing global signals; apart from the regions mentioned above, decreased in bilateral cuneus and calcarine was also showed. Furthermore, the mean VMHC values of the left cerebellum were negatively correlated with the obsession scores (ρ = -.204, π = .039). The decreased values in right fusiform and putamen were negatively correlated with duration of disease (ρ = -.205, π = .038; ρ = -.196, π = .047). We confirmed a significant VMHC reduction in OCD patients in broad areas. Our findings suggest that the patients tend to disconnect information exchange across hemispheres.

Mapping the neuroanatomical heterogeneity of OCD using a framework integrating normative model and non-negative matrix factorization.

Obsessive-compulsive disorder (OCD) is a spectrum disorder with high interindividual heterogeneity. We propose a comprehensible framework integrating normative model and non-negative matrix factorization (NMF) to quantitatively estimate the neuroanatomical heterogeneity of OCD from a dimensional perspective. T1-weighted magnetic resonance images of 98 first-episode untreated patients with OCD and matched healthy controls (HCs, n = 130) were acquired. We derived individualized differences in gray matter morphometry using normative model and parsed them into latent disease factors using NMF. Four robust disease factors were identified. Each patient expressed multiple factors and exhibited a unique factor composition. Factor compositions of patients were significantly correlated with severity of symptom, age of onset, illness duration, and exhibited sex differences, capturing sources of clinical heterogeneity. In addition, the group-level morphological differences obtained with two-sample t test could be quantitatively derived from the identified disease factors, reconciling the group-level and subject-level findings in neuroimaging studies. Finally, we uncovered two distinct subtypes with opposite morphological differences compared with HCs from factor compositions. Our findings suggest that morphological differences of individuals with OCD are the unique combination of distinct neuroanatomical patterns. The proposed framework quantitatively estimating neuroanatomical heterogeneity paves the way for precision medicine in OCD.

Identification of shared and distinct patterns of brain network abnormality across mental disorders through individualized structural covariance network analysis.

BACKGROUND: Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders. METHODS: Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed. RESULTS: Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network. CONCLUSIONS: These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

Structural and functional deficits and couplings in severe and moderate OCD.

Changes in gray matter volume and functional connections have been frequently observed in patients with obsessive compulsive disorder. However, different grouping may cause diverse volume alterations and could draw more adverse conclusions about the pathophysiology of obsessive compulsive disorder(OCD). Most of them preferred to divide subjects into patients and healthy controls, rather than a detailed subgroup. Moreover, multimodal neuroimaging studies about structural-functional defects and couplings are rather rare. Our aim was to explore gray matter volume(GMV) and functional networks abnormalities induced by structural deficits based on severity of Yale-Brown Obsessive Compulsive Scale(Y-BOCS) symptom including OCD patients with severe(S-OCD, n = 31) and moderate symptoms(M-OCD, n = 42) and healthy controls (HCs, n = 54); Voxel-based morphometry(VBM) method was used to detect GMV differences among three groups, then used as masks according to one-way analysis of variance(ANOVA) results for the subsequent resting-state functional connectivity(rs-FC) analysis. Besides, correlation and subgroup analysis were performed to detect the potential roles of structural deficits between every two groups. ANOVA analysis showed that both S-OCD and M-OCD had increased volume in anterior cingulate cortex(ACC), left precuneus(L-Pre) and paracentral lobule(PCL), postcentral gyrus, left inferior occipital gyrus(L-IOG) and right superior occipital gyrus(R-SOG) and bilateral cuneus, middle occipital gyrus(MOG), and calcarine. Additionally, increased connections between Pre and angular gyrus(AG) and inferior parietal lobule(IPL) have been found. Moreover, connections between the left cuneus and lingual gyrus, between IOG and left lingual gyrus, fusiform and between L-MOG and cerebellum were also included. Subgroup analysis showed that decreased GMV in left caudate was negatively correlated with compulsion and total score in patients with moderate symptom compared to HCs. Our findings indicated that altered GMV in occipital-related regions, Pre, ACC and PCL and the disrupted FC networks including MOG-cerebellum and Pre-AG and IPL. Moreover, subgroup GMV analysis furtherly revealed negative associations between GMV changes and Y-BOCS symptom, offering preparatory proof for the involvement of structural and functional deficits in cortical-subcortical circuitry. Thus, they could provide insights into the neurobiological basis.

Resolving heterogeneity in obsessive-compulsive disorder through individualized differential structural covariance network analysis.

BACKGROUND: The high heterogeneity of obsessive-compulsive disorder (OCD) denies attempts of traditional case-control studies to derive neuroimaging biomarkers indicative of precision diagnosis and treatment. METHODS: To handle the heterogeneity, we uncovered subject-level altered structural covariance by adopting individualized differential structural covariance network (IDSCN) analysis. The IDSCN measures how structural covariance edges in a patient deviated from those in matched healthy controls (HCs) yielding subject-level differential edges. One hundred patients with OCD and 106 HCs were recruited and whose T1-weighted anatomical images were acquired. We obtained individualized differential edges and then clustered patients into subtypes based on these edges. RESULTS: Patients presented tremendously low overlapped altered edges while frequently shared altered edges within subcortical-cerebellum network. Two robust neuroanatomical subtypes were identified. Subtype 1 presented distributed altered edges while subtype 2 presented decreased edges between default mode network and motor network compared with HCs. Altered edges in subtype 1 predicted the total Yale-Brown Obsessive Compulsive Scale score while that in subtype 2 could not. CONCLUSIONS: We depict individualized structural covariance aberrance and identify that altered connections within subcortical-cerebellum network are shared by most patients with OCD. These 2 subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of OCD.

White matter microstructural abnormalities and gray matter volume alterations in obsessive-compulsive disorder: A coordinate-based meta-analysis.

OBJECTIVE: A comprehensive meta-analysis using correlated coordinate data to explore abnormalities in white matter (WM) microarchitecture and changes in gray matter volume (GMV) in patients with obsessive-compulsive disorder (OCD). METHODS: We reviewed 23 reported studies of diffusion tensor imaging (DTI) in OCD patients. The differences in WM fractional anisotropy (FA) between OCD patients and healthy controls (HCs) were investigated using tract-based spatial statistics (TBSS) and voxel-based analysis (VBA), respectively, and the results of the two methods were compared. In addition, we will explore changes in OCD GMV by analyzing studies (n = 21) using the voxel-based morphometry (VBM) approach and comparing the difference between adults and adolescents. RESULTS: In the pooled meta-analysis, WM study results presented that compared with HCs, OCD patients had higher FA in right lenticular nucleus (putamen), and lower FA in corpus callosum (CC), left insula, right cerebellum (hemispheric lobule), right gyrus rectal and left inferior parietal gyri. However, in subgroup analysis, there was a significant difference in FA changes between TBSS and VBA in OCD patients compared with HCs. In addition, we found that the GMV of OCD patients was significantly increased in left striatum and left precentral gyrus, and significantly decreased in right inferior frontal gyrus triangular part, right superior temporal gyrus and right hippocampus. Compared with adolescents, adult patients have increased GMV in left lenticular nucleus putamen. CONCLUSION: The meta-analysis showed that OCD patients had abnormal WM microarchitecture and altered GMV. These changes may be closely related to the pathophysiological mechanism of the disease.

Altered time-varying local spontaneous brain activity pattern in patients with high myopia: a dynamic amplitude of low-frequency fluctuations study.

PURPOSE: To investigate the abnormal time-varying local spontaneous brain activity in patients with high myopia (HM) on the basis of the dynamic amplitude of low-frequency fluctuations (dALFF) approach. METHODS: Age and gender matching were performed based on resting-state functional magnetic resonance imaging data from 86 HM patients and 87 healthy controls (HCs). Local spontaneous brain activities were evaluated using the time-varying dALFF method. Support vector machine combined with the radial basis function kernel was used for pattern classification analysis. RESULTS: Inter-group comparison between HCs and HM patients has demonstrated that dALFF variability in the left inferior frontal gyrus (orbital part), left lingual gyrus, right anterior cingulate and paracingulate gyri, and right calcarine fissure and surrounding cortex was decreased in HM patients, while increased in the left thalamus, left paracentral lobule, and left inferior parietal (except supramarginal and angular gyri). Pattern classification between HM patients and HCs displayed a classification accuracy of 85.5%. CONCLUSION: In this study, the findings mentioned above have suggested the association between local brain activities of HM patients and abnormal variability in brain regions performing visual sensorimotor and attentional control functions. Several useful information has been provided to elucidate the mechanism-related alterations of the myopic nervous system. In addition, the significant role of abnormal dALFF variability has been highlighted to achieve an in-depth comprehension of the pathological alterations and neuroimaging mechanisms in the field of HM.

Two distinct subtypes of obsessive compulsive disorder revealed by a framework integrating multimodal neuroimaging information.

Patients with obsessive compulsive disorder (OCD) exhibit tremendous heterogeneity in structural and functional neuroimaging aberrance. However, most previous studies just focus on group-level aberrance of a single modality ignoring heterogeneity and multimodal features. On that account, we aimed to uncover OCD subtypes integrating structural and functional neuroimaging features with the help of a multiview learning method and examined multimodal aberrance for each subtype. Ninety-nine first-episode untreated patients with OCD and 104 matched healthy controls (HCs) undergoing structural and functional MRI were included in this study. Voxel-based morphometric and amplitude of low-frequency fluctuation (ALFF) were adopted to assess gray matter volumes (GMVs) and the spontaneous neuronal fluctuations respectively. Structural/functional distance network was obtained by calculating Euclidean distance between pairs of regional GMVs/ALFF values across patients. Similarity network fusion, one of multiview learning methods capturing shared and complementary information from multimodal data sources, was used to fuse multimodal distance networks into one fused network. Then spectral clustering was adopted to categorize patients into subtypes. As a result, two robust subtypes were identified. These two subtypes presented opposite GMV aberrance and distinct ALFF aberrance compared with HCs while shared indistinguishable clinical and demographic features. In addition, these two subtypes exhibited opposite structure-function difference correlation reflecting distinct adaptive modifications between multimodal aberrance. Altogether, these results uncover two objective subtypes with distinct multimodal aberrance and provide a new insight into taxonomy of OCD.

Altered Coupling of Cerebral Blood Flow and Functional Connectivity Strength in First-Episode Schizophrenia Patients With Auditory Verbal Hallucinations.

Objective: Auditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia with AVHs, alterations in resting-state cerebral blood flow (CBF) and functional connectivity have been described. However, the neurovascular coupling alterations specific to first-episode drug-naïve schizophrenia (FES) patients with AVHs remain unknown. Methods: Resting-state functional MRI and arterial spin labeling (ASL) was performed on 46 first-episode drug-naïve schizophrenia (FES) patients with AVHs (AVH), 39 FES drug-naïve schizophrenia patients without AVHs (NAVH), and 48 healthy controls (HC). Then we compared the correlation between the CBF and functional connection strength (FCS) of the entire gray matter between the three groups, as well as the CBF/FCS ratio of each voxel. Correlation analyses were performed on significant results between schizophrenia patients and clinical measures scale. Results: The CBF/FCS ratio was reduced in the cognitive and emotional brain regions in both the AVH and NAVH groups, primarily in the crus I/II, vermis VI/VII, and cerebellum VI. In the AVH group compared with the HC group, the CBF/FCS ratio was higher in auditory perception and language-processing areas, primarily the left superior and middle temporal gyrus (STG/MTG). The CBF/FCS ratio in the left STG and left MTG positively correlates with the score of the Auditory Hallucination Rating Scale in AVH patients. Conclusion: These findings point to the difference in neurovascular coupling failure between AVH and NAVH patients. The dysfunction of the forward model based on the predictive and computing role of the cerebellum may increase the excitability in the auditory cortex, which may help to understand the neuropathological mechanism of AVHs.

Static and temporal dynamic changes of intrinsic brain activity in pediatric and adults OCD.

Epidemiological and clinical age differences in obsessive-compulsive disorder (OCD) have been reported in clinical symptoms and morphometry changes; however, age differences in amplitude of low-frequency fluctuation and the relationship between ALFF imaging and clinical symptoms has not been thoroughly studied in OCD. Age may be an important feature associated with distinct subtypes of OCD. To examine the effect of age on OCD, the current study enrolled 92 OCD patients (32 pediatrics and 60 adults) and matched HCs (33 pediatrics and 84 adults), undergoing resting-state functional magnetic resonance imaging. The spontaneous brain activity was measured by static and dynamic amplitude of low-frequency fluctuation (ALFF) followed by two-way ANOVA. In pediatric OCD patients versus adult patients, we observed a significantly higher ALFF in the default mode network (DMN), including posterior cingulate, precuneus and superior frontal gyrus, and extending to cuneus, lingual gyrus. Additionally, the increased ALFF and dynamic ALFF in the precentral gyrus were found in pediatric patients. In OCD patients compared with controls, we found a significantly increased ALFF in hippocampal gyrus, cerebellum network (CN), and the dALFF in middle and inferior occipital gyrus, bilateral paracentral lobule and sensorimotor network. The findings emphasized the different patterns of static and dynamic intrinsic brain activity alterations associated with pediatric and adult OCD patients. These results provide unique insights into constructing evidenced-based distinct OCD subtypes based on brain activity and point the need of specified management for pediatric and adult OCD patients in clinical setting.

Two distinct subtypes of obsessive compulsive disorder revealed by heterogeneity through discriminative analysis.

Neurobiological heterogeneity in obsessive compulsive disorder (OCD) is understudied leading to conflicting neuroimaging findings. Therefore, we investigated objective neuroanatomical subtypes of OCD by adopting a newly proposed method based on gray matter volumes (GMVs). GMVs were derived from T1-weighted anatomical images of patients with OCD (n = 100) and matched healthy controls (HCs; n = 106). We first inquired whether patients with OCD presented higher interindividual variability HCs in terms of GMVs. Then, we identified distinct subtypes of OCD by adopting heterogeneity through discriminative analysis (HYDRA), where regional GMVs were treated as features. Patients with OCD presented higher interindividual variability than HCs, suggesting a high structural heterogeneity of OCD. HYDRA identified two distinct robust subtypes of OCD presenting opposite neuroanatomical aberrances compared with HCs, while sharing indistinguishable clinical and demographic features. Specifically, Subtype 1 exhibited widespread increased GMVs in cortical and subcortical regions, including the orbitofrontal gyrus, right anterior insula, bilateral hippocampus, and bilateral parahippocampus and cerebellum. Subtype 2 demonstrated overall decreased GMVs in regions such as the orbitofrontal gyrus, right anterior insula, and precuneus. When mixed together, none of patients presented significant differences compared with HCs. In addition, the total intracranial volume of Subtype 2 was significantly correlated with the total score of the Yale-Brown Obsessive Compulsive Scale while that of Subtype 1 was not. These results identified two distinct neuroanatomical subtypes, providing a possible explanation for conflicting neuroimaging findings, and proposed a potential objective taxonomy contributing to precise clinical diagnosis and treatment in OCD.