Dataset Information

Salience-Default Mode Functional Network Connectivity Linked to Positive and Negative Symptoms of Schizophrenia.

ABSTRACT: Schizophrenia is a complex, debilitating mental disorder characterized by wide-ranging symptoms including delusions, hallucinations (so-called positive symptoms), and impaired motor and speech/language production (so-called negative symptoms). Salience-monitoring theorists propose that abnormal functional communication between the salience network (SN) and default mode network (DMN) begets positive and negative symptoms of schizophrenia, yet prior studies have predominately reported links between disrupted SN/DMN functional communication and positive symptoms. It remains unclear whether disrupted SN/DMN functional communication explains (1) solely positive symptoms or (2) both positive and negative symptoms of schizophrenia. To address this question, we incorporate time-lag-shifted functional network connectivity (FNC) analyses that explored coherence of the resting-state functional magnetic resonance imaging signal of 3 networks (anterior DMN, posterior DMN, and SN) with fixed time lags introduced between network time series (1 TR = 2 s; 2 TR = 4 s). Multivariate linear regression analysis revealed that severity of disordered thought and attentional deficits were negatively associated with 2 TR-shifted FNC between anterior DMN and posterior DMN. Meanwhile, severity of flat affect and bizarre behavior were positively associated with 1 TR-shifted FNC between anterior DMN and SN. These results provide support favoring the hypothesis that lagged SN/DMN functional communication is associated with both positive and negative symptoms of schizophrenia.

SUBMITTER: Hare SM

PROVIDER: S-EPMC6581131 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Salience-Default Mode Functional Network Connectivity Linked to Positive and Negative Symptoms of Schizophrenia.

Hare Stephanie M SM Ford Judith M JM Mathalon Daniel H DH Damaraju Eswar E Bustillo Juan J Belger Aysenil A Lee Hyo Jong HJ Mueller Bryon A BA Lim Kelvin O KO Brown Gregory G GG Preda Adrian A van Erp Theo G M TGM Potkin Steven G SG Calhoun Vince D VD Turner Jessica A JA

Schizophrenia bulletin 20190601 4

Schizophrenia is a complex, debilitating mental disorder characterized by wide-ranging symptoms including delusions, hallucinations (so-called positive symptoms), and impaired motor and speech/language production (so-called negative symptoms). Salience-monitoring theorists propose that abnormal functional communication between the salience network (SN) and default mode network (DMN) begets positive and negative symptoms of schizophrenia, yet prior studies have predominately reported links betwee ...[more]

PMID: 30169884

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Project description:Schizophrenia and autism spectrum disorder (ASD) are two prevalent neurodevelopmental disorders sharing some similar genetic basis and clinical features. The extent to which they share common neural substrates remains unclear. Resting-state fMRI data were collected from 35 drug-naïve adolescent participants with first-episode schizophrenia (15.6 ± 1.8 years old) and 31 healthy controls (15.4 ± 1.6 years old). Data from 22 participants with ASD (13.1 ± 3.1 years old) and 21 healthy controls (12.9 ± 2.9 years old) were downloaded from the Autism Brain Imaging Data Exchange. Resting-state functional networks were constructed using predefined regions of interest. Multivariate pattern analysis combined with multi-task regression feature selection methods were conducted in two datasets separately. Classification between individuals with disorders and controls was achieved with high accuracy (schizophrenia dataset: accuracy = 83%; ASD dataset: accuracy = 80%). Shared atypical brain connections contributing to classification were mostly present in the default mode network (DMN) and salience network (SN). These functional connections were further related to severity of social deficits in ASD (p = 0.002). Distinct atypical connections were also more related to the DMN and SN, but showed different atypical connectivity patterns between the two disorders. These results suggest some common neural mechanisms contributing to schizophrenia and ASD, and may aid in understanding the pathology of these two neurodevelopmental disorders. Autism Res 2017, 10: 1776-1786. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay summaryAutism spectrum disorder (ASD) and schizophrenia are two common neurodevelopmental disorders which share several genetic and behavioral features. The present study identified common neural mechanisms contributing to ASD and schizophrenia using resting-state functional MRI data. The results may help to understand the pathology of these two neurodevelopmental disorders.

Project description:IntroductionDynamic functional network connectivity (dFNC) analysis of resting state functional magnetic resonance imaging data has yielded insights into many neurological and neuropsychiatric disorders. A common dFNC analysis approach uses hard clustering methods like k-means clustering to assign samples to states that summarize network dynamics. However, hard clustering methods obscure network dynamics by assuming (1) that all samples within a cluster are equally like their assigned centroids and (2) that samples closer to one another in the data space than to their centroids are well-represented by their centroids. In addition, it can be hard to compare subjects, as in some cases an individual may not manifest a state strongly enough to enter a hard cluster. Approaches that allow a dimensional approach to connectivity patterns (e.g., fuzzy clustering) can mitigate these issues. In this study, we present an explainable fuzzy clustering framework by combining fuzzy c-means clustering with several explainability metrics and novel summary features.MethodsWe apply our framework for schizophrenia (SZ) default mode network analysis. Namely, we extract dFNC from individuals with SZ and controls, identify 5 dFNC states, and characterize the dFNC features most crucial to those states with a new perturbation-based clustering explainability approach. We then extract several features typically used in hard clustering and further present a variety of unique features specially designed for use with fuzzy clustering to quantify state dynamics. We examine differences in those features between individuals with SZ and controls and further search for relationships between those features and SZ symptom severity.ResultsImportantly, we find that individuals with SZ spend more time in states of moderate anticorrelation between the anterior and posterior cingulate cortices and strong anticorrelation between the precuneus and anterior cingulate cortex. We further find that individuals with SZ tend to transition more rapidly than controls between low-magnitude and high-magnitude dFNC states.ConclusionWe present a novel dFNC analysis framework and use it to identify effects of SZ upon network dynamics. Given the ease of implementing our framework and its enhanced insight into network dynamics, it has great potential for use in future dFNC studies.

Dataset Information

Salience-Default Mode Functional Network Connectivity Linked to Positive and Negative Symptoms of Schizophrenia.

Publications

Salience-Default Mode Functional Network Connectivity Linked to Positive and Negative Symptoms of Schizophrenia.

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