Altered Global Brain Functional Connectivity in Drug-Naive Patients With Obsessive-Compulsive Disorder.
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ABSTRACT:
SUBMITTER: Cui G
PROVIDER: S-EPMC7062961 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Obsessive-compulsive disorder (OCD) is a debilitating and disabling neuropsychiatric disorder, whose neurobiological basis remains unclear. Although traditional static resting-state magnetic resonance imaging (rfMRI) studies have found aberrant functional connectivity (FC) in OCD, alterations in whole-brain FC and topological properties in the context of brain dynamics remain relatively unexplored. The rfMRI data of 29 patients with OCD and 40 healthy controls were analyzed using group independent component analysis to obtain independent components (ICs) and a sliding-window approach to generate dynamic functional connectivity (dFC) matrices. dFC patterns were clustered into three reoccurring states, and state transition metrics were obtained. Then, graph-theory methods were applied to dFC matrices to calculate the variability of network topological organization. The occurrence of a state (State 1) with the highest modularity index and lowest mean FC between networks was increased significantly in OCD, and the fractional time in brain State 1 was positively correlated with anxiety level in patients. State 1 was characterized by having positive connections within default mode (DMN) and salience networks (SAN), and negative coupling between the two networks. Additionally, ICs belonging to DMN and SAN showed lower temporal variability of nodal degree centrality and efficiency in patients, which was related to longer illness duration and higher current obsession ratings. Our results provide evidence of clinically relevant aberrant dynamic brain activity in OCD. Increased functional segregation among networks and impaired functional flexibility in connections among brain regions in DMN and SAN may play important roles in the neuropathology of OCD.
| S-EPMC8046074 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) patients have difficulty in switching between obsessive thought and compulsive behavior, which may be related to the dysfunction of the salience network (SN). However, little is known about the changes in intra- and inter- intrinsic functional connectivity (iFC) of the SN in patients with OCD. In this study, we parceled the SN into 19 subregions and investigated iFC changes for each of these subregions in 40 drug-naïve patients with OCD and 40 healthy controls (HCs) using seed-based functional connectivity resting-state functional magnetic resonance imaging (rs-fMRI). We found that patients with OCD exhibited decreased iFC strength between subregions of the SN, as well as decreased inter-network connectivity between SN and DMN, and ECN. These findings highlight a specific alteration in iFC patterns associated with SN in patients with OCD and provide new insights into the dysfunctional brain organization of the SN in patients with OCD.
| S-EPMC6279930 | biostudies-literature
Project description:BackgroundPrevious studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear.MethodsA total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier.ResultsPatients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%.ConclusionAltered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.
| S-EPMC8443365 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.
| S-EPMC5548868 | biostudies-other
Project description:BackgroundRecent studies have shown that response inhibition is impaired in patients with obsessive-compulsive disorder and their unaffected siblings, suggesting that these deficits may be considered a cognitive endophenotype of obsessive-compulsive disorder. Structural and functional neural correlates of altered response inhibition have been identified in patients and siblings. This study aims to examine the functional integrity of the response inhibition network in patients with obsessive-compulsive disorder and their unaffected siblings.MethodsForty-one unmedicated patients with obsessive-compulsive disorder, 17 of their unaffected siblings and 37 healthy controls performed a stop signal task during functional magnetic resonance imaging. Psycho-physiological interaction analysis was used to examine functional connectivity between the following regions of interest: the bilateral inferior frontal gyri, presupplementary motor area, subthalamic nuclei, inferior parietal lobes, anterior cingulate cortex, and amygdala. We then used dynamic causal modeling to investigate the directionality of the networks involved.ResultsPatients, and to a lesser extent also their unaffected siblings, show altered connectivity between the inferior frontal gyrus and the amygdala during response inhibition. The follow-up dynamic causal modeling suggests a bottom-up influence of the amygdala on the inferior frontal gyrus in healthy controls, whereas processing occurs top-down in patients with obsessive-compulsive, and in both directions in siblings.ConclusionsOur findings suggest that amygdala activation in obsessive-compulsive disorder interferes differently with the task-related recruitment of the inhibition network, underscoring the role of limbic disturbances in cognitive dysfunctions in obsessive-compulsive disorder.
| S-EPMC6869170 | biostudies-literature
Project description:Background: Neuroimaging studies have shown that the high synchrony of spontaneous neural activity in the homotopic regions between hemispheres is an important functional structural feature of normal human brains, and this feature is abnormal in the patients with various mental disorders. However, little is known about this feature in obsessive-compulsive disorder (OCD). This study aimed to further analyze the underlying neural mechanisms of OCD and to explore whether clinical characteristics are correlated with the alerted homotopic connectivity in patients with OCD. Methods: Using voxel-mirrored homotopic connectivity (VMHC) during resting state, we compared 46 OCD patients and 46 healthy controls (HCs) matched for age, gender, and education level. A partial correlation analysis was used to investigate the relationship between altered VMHC and clinical characteristics in patients with OCD. Results: Patients with OCD showed lower VMHC than HCs in fusiform gyrus/inferior occipital gyrus, lingual gyrus, postcentral gyrus/precentral gyrus, putamen, and orbital frontal gyrus. A significant positive correlation was observed between altered VMHC in the angular gyrus/middle occipital gyrus and illness duration in patients. Conclusions: Interhemispheric functional imbalance may be an essential aspect of the pathophysiological mechanism of OCD, which is reflected not only in the cortico-striato-thalamo-cortical (CSTC) loop but also elsewhere in the brain.
| S-EPMC6584782 | biostudies-literature
Project description:Fronto-striatal circuits are hypothesized to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). Within this circuitry, ventral frontal regions project fibers to the ventral striatum (VS) and dorsal frontal regions to the dorsal striatum. Resting state fMRI research has shown higher functional connectivity between the orbitofrontal cortex (OFC) and the dorsal part of the VS in OCD patients compared to healthy controls (HC). Therefore, we hypothesized that in OCD the OFC predominantly project fibers to the more dorsal part of the VS, and that the structural connectivity between the OFC and VS is higher compared to HC. A total of 20 non-medicated OCD patients and 20 HC underwent diffusion-weighted imaging. Connectivity-based parcellation analyses were performed with the striatum as seed region and the OFC, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex as target regions. Obtained connectivity maps for each frontal region of interest (ROI) were normalized into standard space, and Z-component (dorsal-ventral) coordinate of center-of-gravity (COG) were compared between two groups. Probabilistic tractography was performed to investigate diffusion indices of fibers between the striatum and frontal ROIs. COG Z-component coordinates of connectivity maps for OFC ROI were located in the more dorsal part of the VS in OCD patients compared to HC. Fractional anisotropy of fibers between the OFC and the striatum was higher in OCD patients compared to HC. Part of the pathophysiology of OCD might be understood by altered topography and structural connectivity of fibers between the OFC and the striatum.
| S-EPMC4222976 | biostudies-literature
Project description:BackgroundBased on findings from adults with obsessive-compulsive disorder (OCD), this study examined alterations in resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA-vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first-line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning-a probable mechanism of action of E/RP.MethodsResting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age- and sex-matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12-16-week E/RP intervention for OCD. Participants were rescanned after the 12-16-week period. ANCOVAs tested group differences in baseline rs-fc. Cross-lagged panel models examined relationships between BLA-vmPFC rs-fc and OCD symptoms pre- and posttreatment. All tests were adjusted for participants' age, sex, and head motion.ResultsRight BLA-vmPFC rs-fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA-vmPFC rs-fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to posttreatment.ConclusionsThese results provide further evidence of the BLA-vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.
| S-EPMC8328961 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) is a chronic and disablingpsychiatric disorder with high lifetime prevalence, yet the underlying pathogenesis remains not fully understood. Increasing neuroimaging evidence has shown that the disrupted activity of brain functional hubs might contribute to the pathophysiology of OCD. Precuneus is an important brain hub which showed structural and functional abnormalities in OCD patients. However, the functional heterogeneity of the precuneus subregion has not been considered and its relation to OCD symptomatology remains to be elucidated. In this paper, a total of 73 unmedicated OCD patients and 79 matched healthy subjects were recruited and the heterogeneous functional connectivities (FCs) of the precuneus subregions were investigated using resting-state functional magnetic resonance imaging. The FC-based subdivision of the precuneus was performed using the K-means clustering algorithm, which led to a tripartite functional parcellation of precuneus. For each subregion, the distinct connectivity pattern with the whole brain was shown, using both voxel-wise and module-wise analysis, respectively. Decreased FC between dorsal posterior precuneus and vermis (corrected p<0.01) was shown in the patient group, which was negatively correlated with patient compulsions score (ρ = - 0.393, p = 0.001), indicating its contribution to the compulsive behavior inhibition of OCD. Our work might provide new insights into the understanding of precuneus subregion function and the importance of dorsal precuneus-cerebellum functional connectivity in OCD pathophysiology.
| S-EPMC8220401 | biostudies-literature
Project description:IntroductionObsessive-compulsive disorder (OCD), characterized by the presence of obsessions and/or compulsions, is often difficult to diagnose and treat in routine clinical practice. The candidate circulating biomarkers and primary metabolic pathway alteration of plasma in OCD remain poorly understood.MethodsWe recruited 32 drug-naïve patients with severe OCD and 32 compared healthy controls and applied the untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to assess their circulating metabolic profiles. Both univariate and multivariate analyses were then utilized to filtrate differential metabolites between patients and healthy controls, and weighted Correlation Network Analysis (WGCNA) was utilized to screen out hub metabolites.ResultsA total of 929 metabolites were identified, including 34 differential metabolites and 51 hub metabolites, with an overlap of 13 metabolites. Notably, the following enrichment analyses underlined the importance of unsaturated fatty acids and tryptophan metabolism alterations in OCD. Metabolites of these pathways in plasma appeared to be promising biomarkers, such as Docosapentaenoic acid and 5-Hydroxytryptophan, which may be biomarkers for OCD identification and prediction of sertraline treatment outcome, respectively.ConclusionOur findings revealed alterations in the circulating metabolome and the potential utility of plasma metabolites as promising biomarkers in OCD.
| S-EPMC10272357 | biostudies-literature