Enhanced Connectivity of Thalamo-Cortical Networks in First-Episode, Treatment-Naive Somatization Disorder
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ABSTRACT:
SUBMITTER: Zhao J
PROVIDER: S-EPMC7518236 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:The nucleus accumbens (NAc) plays an important role in the reward circuit, and abnormal regional activities of the reward circuit have been reported in various psychiatric disorders including somatization disorder (SD). However, few researches are designed to analyze the NAc connectivity in SD. This study was designed to explore the NAc connectivity in first-episode, drug-naive patients with SD using the bilateral NAc as seeds. Twenty-five first-episode, drug-naive patients with SD and 28 healthy controls were recruited. Functional connectivity (FC) was designed to analyze the images. LIBSVM (a library for support vector machines) was used to identify whether abnormal FC could be utilized to discriminate the patients from the controls. The patients showed significantly increased FC between the left NAc and the right gyrus rectus and left medial prefrontal cortex/anterior cingulate cortex (MPFC/ACC), and between the right NAc and the left gyrus rectus and left MPFC/ACC compared with the controls. The patients could be separated from the controls through increased FC between the left NAc and the right gyrus rectus with a sensitivity of 88.00% and a specificity of 82.14%. The findings reveal that patients with SD have increased NAc connectivity with the frontal regions of the reward circuit. Increased left NAc-right gyrus rectus connectivity can be used as a potential marker to discriminate patients with SD from healthy controls. The study thus highlights the importance of the reward circuit in the neuropathology of SD.
| S-EPMC6706814 | biostudies-literature
Project description:Background: Anatomical and functional deficits in the cortico-limbic-cerebellar circuit are involved in the neurobiology of somatization disorder (SD). The present study was performed to examine causal connectivity of the cortico-limbic-cerebellar circuit related to structural deficits in first-episode, drug-naive patients with SD at rest. Methods: A total of 25 first-episode, drug-naive patients with SD and 28 healthy controls underwent structural and resting-state functional magnetic resonance imaging. Voxel-based morphometry and Granger causality analysis (GCA) were used to analyze the data. Results: Results showed that patients with SD exhibited decreased gray matter volume (GMV) in the right cerebellum Crus I, and increased GMV in the left anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left angular gyrus. Causal connectivity of the cortico-limbic-cerebellar circuit was partly affected by structural alterations in the patients. Patients with SD showed bidirectional cortico-limbic connectivity abnormalities and bidirectional cortico-cerebellar and limbic-cerebellar connectivity abnormalities. The mean GMV of the right MFG was negatively correlated with the scores of the somatization subscale of the symptom checklist-90 and persistent error response of the Wisconsin Card Sorting Test (WCST) in the patients. A negative correlation was observed between increased driving connectivity from the right MFG to the right fusiform gyrus/cerebellum IV, V and the scores of the Eysenck Personality Questionnaire extraversion subscale. The mean GMV of the left ACC was negatively correlated with the WCST number of errors and persistent error response. Negative correlation was found between the causal effect from the left ACC to the right middle temporal gyrus and the scores of WCST number of categories achieved. Conclusions: Our findings show the partial effects of structural alterations on the cortico-limbic-cerebellar circuit in first-episode, drug-naive patients with SD. Correlations are observed between anatomical alterations or causal effects and clinical variables in patients with SD, and bear clinical significance. The present study emphasizes the importance of the cortico-limbic-cerebellar circuit in the neurobiology of SD.
| S-EPMC5932337 | biostudies-literature
Project description:Major depressive disorder (MDD) has been associated with disruptions in the topological organization of brain morphological networks in group-level data. Such disruptions have not yet been identified in single-patients, which is needed to show relations with symptom severity and to evaluate their potential as biomarkers for illness. To address this issue, we conducted a cross-sectional structural brain network study of 33 treatment-naive, first-episode MDD patients and 33 age-, gender-, and education-matched healthy controls (HCs). Weighted graph-theory based network models were used to characterize the topological organization of brain networks between the two groups. Compared with HCs, MDD patients exhibited lower normalized global efficiency and higher modularity in their whole-brain morphological networks, suggesting impaired integration and increased segregation of morphological brain networks in the patients. Locally, MDD patients exhibited lower efficiency in anatomic organization for transferring information predominantly in default-mode regions including the hippocampus, parahippocampal gyrus, precuneus and superior parietal lobule, and higher efficiency in the insula, calcarine and posterior cingulate cortex, and in the cerebellum. Morphological connectivity comparisons revealed two subnetworks that exhibited higher connectivity strength in MDD mainly involving neocortex-striatum-thalamus-cerebellum and thalamo-hippocampal circuitry. MDD-related alterations correlated with symptom severity and differentiated individuals with MDD from HCs with a sensitivity of 87.9% and specificity of 81.8%. Our findings indicate that single subject grey matter morphological networks are often disrupted in clinically relevant ways in treatment-naive, first episode MDD patients. Circuit-specific changes in brain anatomic network organization suggest alterations in the efficiency of information transfer within particular brain networks in MDD. Hum Brain Mapp 38:2482-2494, 2017. © 2017 Wiley Periodicals, Inc.
| S-EPMC6866860 | biostudies-literature
Project description:ObjectiveGrowing evidence has implicated dysfunction of the thalamus and its projection cortical targets in depression. However, the anatomical specificity of thalamo-cortical connectivity in major depressive disorder (MDD) remains unknown due to the regional heterogeneity of the thalamus and limited methods to examine this.MethodsResting-state fMRI was collected on 70 MDD patients and 70 healthy controls. The thalamus was parcellated based on connectivity with six predefined cortical regions of interest (ROIs). The segmented thalamic nuclei were used as seeds to map connectivity with the rest of the whole brain. The cortical-to-thalamus connectivity values and thalamus-based connectivity maps were compared between groups.ResultsThe cortical ROIs demonstrated correlations with spatially distinct zones within the thalamus. We found a trend toward reduced parietal ROI-to-thalamus connectivity in MDD. Importantly, MDD patients demonstrated reduced connectivity between prefrontal and parietal thalamus ROIs and bilateral middle frontal gyrus (MFG) and the right posterior default mode network (DMN) and between the prefrontal and motor thalamus ROIs and lateral temporal regions. Conversely, increased connectivity emerged between the motor thalamus ROI and right MFG and right medial frontal gyrus/anterior cingulate; between motor/somatosensory thalamus ROIs and right posterior DMN; between prefrontal/somatosensory thalamus ROIs and cerebellum; and between the parietal thalamus ROI and left insula.ConclusionsThis study is the first to examine the anatomical specificity of thalamo-cortical connectivity disturbances in MDD. Subjects with MDD demonstrated altered thalamo-cortical connectivity characterized by a complex pattern of region-dependent hypo- or hyperconnectivity. We therefore speculate that selectively modulating the connectivity of thalamo-cortical circuitry may be a potential novel therapeutic mechanism for MDD.
| S-EPMC6490069 | biostudies-literature
Project description:Background:The investigation of large-scale intrinsic connectivity networks in antipsychotic-naïve first-episode schizophrenia increases our understanding of system-level cerebral dysfunction in schizophrenia while enabling control of confounding effects of medication and disease progression. Reports on functional connectivity in antipsychotic-naïve patients have been mixed and the relation between network alterations, psychopathology and cognition is unclear. Methods:A total number of 47 patients with first-episode schizophrenia who had never received antipsychotic medication and 47 healthy controls were scanned with functional magnetic resonance imaging under resting conditions. Main outcome measures were differences in functional connectivity between groups and the relationship between network alterations, psychopathology and cognition. Results:Altered connectivity was found between right central executive network (CEN) and right ventral attention network (VAN) (patients > controls, P = .001), left CEN and left VAN (P = .002), and between posterior default mode network and auditory network (P = .006). Association between network connectivity and clinical characteristics was found as interactions between the effects of group and sustained attention (P = .005) and between group and processing speed (P = .007) on the connectivity between right CEN and right VAN. Conclusions:Our findings suggest that the early phase of schizophrenia is characterized by increased connectivity between fronto-parietal networks suggested to be involved in the control of cognitive and sensory functions. Moreover, the present study suggests that the problem of not disengaging the VAN leads to difficulties with attention and possibly subjective awareness.
| S-EPMC6192505 | biostudies-literature
Project description:Objective:The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Method:Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.
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Project description:Analyzing the schizophrenia connectome can identify illness-related alterations in connectivity across the brain. An important question that remains unanswered is whether connectivity alterations are already evident at the onset of illness, before treatment with antipsychotic medication and possible influences of neuroprogressive or secondary alterations related to chronic illness duration. In the present study, diffusion tensor imaging and deterministic fiber tractography were performed with 137 antipsychotic-naive first-episode schizophrenia patients and 113 matched healthy controls. Using graph theoretic analysis, groups were compared in global and regional measurements and modularity of white matter connectivity. Compared with controls, the patients showed significantly decreased total connection strength. Furthermore, patients demonstrated significantly decreased connections within and between brain modules. Several local brain regions within association cortex exhibited reduced nodal centralities and abnormal participant coefficient or intra-module degree, some of which were correlated with illness duration and overall functional disability. In never-treated schizophrenia patients, networks showed a less effective organizational pattern of white matter pathways. White matter disconnectivity occurred not only within but also between multiple modules, shedding light on the deficits of anatomical network organization early in the course of schizophrenia.
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Project description:Some efforts were done to investigate the disruption of brain causal connectivity networks involved in major depressive disorder (MDD) using Granger causality (GC) analysis. However, the homogenous hemodynamic response function (HRF) assumption over the brain may disturb the inference of temporal precedence. Here we applied a blind deconvolution approach to examine the altered HRF shape in first-episode, drug-naïve MDD patients. The regions with abnormal HRF shape in patients were chosen as seeds to detect the GC alterations in MDD. The results demonstrated significantly decreased magnitude of spontaneous hemodynamic response of the orbital frontal cortex (OFC) and the caudate nucleus (CAU) in MDD comparing to healthy controls, suggesting MDD patients likely had alterations in neurovascular coupling and cerebrovascular physiology in these two regions. GC mapping showed increased/decreased GC in OFC-/CAU centered networks in MDD. The outgoing GC values from OFC to anterior cingulate cortex and occipital regions were positively correlated with Hamilton Depression Scale (HAMD) scores, while the incoming GC from insula, middle and superior temporal gyrus to CAU were negatively correlated with HAMD scores of MDD. The abnormalities of directional connections in the cortico-subcortico-cerebellar network may lead to unbalanced integrating the emotional-related information for MDD, and further exacerbating depressive symptoms.
| S-EPMC4766513 | biostudies-other
Project description:Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.
| S-EPMC4838094 | 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