Decreased Intrinsic Functional Connectivity of the Salience Network in Drug-Naive Patients With Obsessive-Compulsive Disorder.
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ABSTRACT:
SUBMITTER: Chen YH
PROVIDER: S-EPMC6279930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abnormal functional connectivity (FC) within discrete brain networks is involved in the pathophysiology of obsessive-compulsive disorder (OCD) with inconsistent results. In the present study, we investigated the FC patterns of 40 drug-naive patients with OCD and 38 healthy controls (HCs) through an unbiased voxel-wise global brain FC (GFC) analysis at rest. Compared with HCs, patients with OCD showed decreased GFC within the default mode network (DMN) (i.e., left posterior cingulate cortex/lingual gyrus) and sensorimotor network (i.e., left precentral gyrus/postcentral gyrus) and increased GFC within the executive control network (ECN) (i.e., left dorsal lateral prefrontal cortex and left inferior parietal lobule). Receiver operating characteristic curve analyses further indicated that the altered GFC values within the DMN, ECN, and sensorimotor network may be used as neuroimaging markers to differentiate patients with OCD from HCs. These findings indicated the aberrant FC patterns of the DMN, ECN, and sensorimotor network associated with the pathophysiology of OCD and provided new insights into the changes in brain organization function in OCD.
| S-EPMC7062961 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) displays alterations in regional brain activity represented by the amplitude of low-frequency fluctuation (ALFF), but the time-varying characteristics of this local neural activity remain to be clarified. We aimed to investigate the dynamic changes of intrinsic brain activity in a relatively large sample of drug-naïve OCD patients using univariate and multivariate analyses. We applied a sliding-window approach to calculate the dynamic ALFF (dALFF) and compared the difference between 73 OCD patients and age- and sex-matched healthy controls (HCs). We also utilized multivariate pattern analysis to determine whether dALFF could differentiate OCD patients from HCs at the individual level. Compared with HCs, OCD patients exhibited increased dALFF mainly within regions of the cortical-striatal-thalamic-cortical (CSTC) circuit, including the bilateral dorsal anterior cingulate cortex, medial prefrontal cortex and striatum, and right dorsolateral prefrontal cortex (dlPFC). Decreased dALFF was identified in the bilateral inferior parietal lobule (IPL), posterior cingulate cortex, insula, fusiform gyrus, and cerebellum. Moreover, we found negative correlations between illness duration and dALFF values in the right IPL and between dALFF values in the left cerebellum and Hamilton Depression Scale scores. Furthermore, dALFF can distinguish OCD patients from HCs with the most discriminative regions located in the IPL, dlPFC, middle occipital gyrus, and cuneus. Taken together, in the current study, we demonstrated a characteristic pattern of higher variability of regional brain activity within the CSTC circuits and lower variability in regions outside the CSTC circuits in drug-naïve OCD patients.
| S-EPMC8288087 | biostudies-literature
Project description:ObjectiveDecreased homotopic connectivity of brain networks such as the cortico-striato-thalamo-cortical (CSTC) circuits may contribute to the pathophysiology of obsessive-compulsive disorder (OCD). However, little is known about interhemispheric functional connectivity (FC) at rest in OCD. In this study, the voxel-mirrored homotopic connectivity (VMHC) method was applied to explore interhemispheric coordination at rest in OCD.MethodsForty medication-free patients with OCD and 38 sex-, age-, and education level-matched healthy controls (HCs) underwent a resting-state functional magnetic resonance imaging. The VMHC and support vector machine (SVM) methods were used to analyze the data.ResultsPatients with OCD had remarkably decreased VMHC values in the orbitofrontal cortex, thalamus, middle occipital gyrus, and precentral and postcentral gyri compared with HCs. A combination of the VMHC values in the thalamus and postcentral gyrus could optimally distinguish patients with OCD from HCs.ConclusionsOur findings highlight the contribution of decreased interhemispheric FC within and outside the CSTC circuits in OCD and provide evidence to the pathophysiology of OCD.
| S-EPMC7522198 | biostudies-literature
Project description:Generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry about everyday life. Prior neuroimaging studies have demonstrated that GAD is associated with disruptions in specific brain regions; however, little is known about the global functional connectivity maps in adolescents with GAD. Here, first-episode, medication-naive, adolescent GAD patients (N = 36) and healthy controls (N = 28) (HCs) underwent resting-state functional MRI (R-fMRI) and completed a package of questionnaires to assess clinical symptoms. Functional connectivity strength and seed-based functional connectivity were employed to investigate the functional connectivity architecture. GAD patients showed reduced functional connectivity strength in right supramarginal gyrus (SMG) and right superior parietal gyrus (SPG) compared with HCs. Further seed-based functional connectivity analysis revealed that GAD patients displayed decreased functional connectivity between right SMG and left fusiform gyrus, inferior temporal gyrus, parahippocampal gyrus, bilateral precuneus and cuneus, and between right SPG and bilateral supplementary motor area and middle cingulate gyrus, as well as between the SMG-based network and the SPG-based network. Moreover, the disrupted intra-network connectivity (i.e., the SMG-based network and the SPG-based network) and inter-network connectivity between the SMG-based network and the SPG-based network accounted for 25.5% variance of the State and Trait Anxiety Inventory (STAI) and 39.5% variance of the trait subscale of STAI. Our findings highlight the abnormal functional architecture in the SMG-based network and the SPG-based network in GAD, providing novel insights into the pathological mechanisms of this disorder.
| S-EPMC6337053 | biostudies-literature
Project description:BackgroundPrevious studies have demonstrated that structural deficits and functional connectivity imbalances might underlie the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of the present study was to investigate gray matter deficits and abnormal resting-state networks in patients with OCD and further investigate the association between the anatomic and functional alterations and clinical symptoms.MethodsParticipants were 33 treatment-naïve OCD patients and 33 matched healthy controls. Voxel-based morphometry was used to investigate the regions with gray matter abnormalities and resting-state functional connectivity analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain.ResultsCompared with healthy controls, patients with OCD showed significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex, as well as decreased gray matter volume in the bilateral medial orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal gyrus. By using the above morphologic deficits areas as seed regions, functional connectivity analysis found abnormal functional integration in the cortical-striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent correlation analyses revealed that morphologic deficits in the left thalamus and increased functional connectivity within the CSTC circuits positively correlated with the total Y-BOCS score.ConclusionThis study provides evidence that morphologic and functional alterations are seen in CSTC circuits and default mode network in treatment-naïve OCD patients. The association between symptom severity and the CSTC circuits suggests that anatomic and functional alterations in CSTC circuits are especially important in the pathophysiology of OCD.
| S-EPMC3865285 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and ritualized, repetitive behaviors, or mental acts. Convergent experimental evidence from neuroimaging and neuropsychological studies supports an orbitofronto-striato-thalamo-cortical dysfunction in OCD. Moreover, an over excitability of the amygdala and over monitoring of thoughts and actions involving the anterior cingulate, frontal and parietal cortex has been proposed as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical approach to investigate brain network organization in 17 unmedicated OCD patients and 19 controls using resting-state fMRI. OCD patients showed a decreased connectivity of the limbic network to several other brain networks: the basal ganglia network, the default mode network, and the executive/attention network. The connectivity within the limbic network was also found to be decreased in OCD patients compared to healthy controls. Furthermore, we found a stronger connectivity of brain regions within the executive/attention network in OCD patients. This effect was positively correlated with disease severity. The decreased connectivity of limbic regions (amygdala, hippocampus) may be related to several neurocognitive deficits observed in OCD patients involving implicit learning, emotion processing and expectation, and processing of reward and punishment. Limbic disconnection from fronto-parietal regions relevant for (re)-appraisal may explain why intrusive thoughts become and/or remain threatening to patients but not to healthy subjects. Hyperconnectivity within the executive/attention network might be related to OCD symptoms such as excessive monitoring of thoughts and behavior as a dysfunctional strategy to cope with threat and uncertainty.
| S-EPMC6868939 | biostudies-literature
Project description:Objective: Obsessive-compulsive disorder (OCD) is characterized by anxiety-provoking, obsessive thoughts (i.e., obsessions) which patients react to with compulsive behaviors (i.e., compulsions). Due to the transient feeling of relief following the reduction of obsession-induced anxiety, compulsions are often described as relieving or even rewarding. Several studies investigated functional activation during reward processing in OCD, but findings are heterogeneous up to now and little is known about potential alterations in functional connectivity. Method: Against this background we studied OCD patients (n = 44) and healthy controls (n = 37) during the receipt of monetary reward by assessing both activation and functional connectivity. Results: Patients showed a decreased activation in several frontal regions and the posterior cingulate (PCC, BA31) together with a stronger connectivity between the PCC and the vmPFC (BA10). Conclusion: Present findings demonstrate an increased connectivity in patients within major nodes of the default mode network (DMN)-a network known to be involved in the evaluation of internal mental states. These results may indicate an increased activity of internal, self-related processing at the expense of a normal responsiveness toward external rewards and incentives. This, in turn, may explain the constant urge for additional reinforcement and patients' inability to inhibit their compulsive behaviors.
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Project description:Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure (n = 16), TS + OCD (n = 14), OCD (n = 11), or controls (n = 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.
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Project description:Deficits in attention have been implicated in Obsessive-Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs-fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN-SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN-SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN-SN networks that subserve attentional processes and this effect of OCD on DMN-SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN-SN connectivity may represent a trans-diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN-SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp 38:678-687, 2017. © 2016 Wiley Periodicals, Inc.
| S-EPMC5225141 | biostudies-literature
Project description:Knowledge of pharmacotherapeutic treatment options in obsessive-compulsive disorder (OCD) has grown considerably over the past 40 years. Serotonergic antidepressants, such as selective serotonin reuptake inhibitors (SSRls) and clomipramine, are the established pharmacologic first-line treatment of OCD. Medium to large dosages and acute treatment for at least 3 months are recommended until efficacy is assessed. In case of significant improvement, maintenance treatment is necessary, Unfortunately, about half of the patients do not respond sufficiently to oral serotonergic antidepressants; augmentation with atypical antipsychotics is an established second-line drug treatment strategy. Alternatives include intravenous serotonergic antidepressants and combination with or switch to cognitive behavioral psychotherapy. Remarkably, a considerable proportion of OCD patients still do not receive rational drug treatment. Novel research approaches, such as preliminary treatment studies with glutamatergic substances, and trials with further drugs, as well as needed aspects of future research, are reviewed.
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