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Social affective context reveals altered network dynamics in schizophrenia patients.

ABSTRACT: Impairments in social cognition and interactions are core psychopathologies in schizophrenia, often manifesting as an inability to appropriately relate to the intentions and feelings of others. Neuroimaging has helped to demarcate the dynamics of two distinct functional connectivity circuits underlying the social-affective processes related to mentalization (known as Theory of Mind, ToM) and somatic-affiliation (known as Embodied Simulation, ES). While evidence points to abnormal activation patterns within these networks among those suffering from schizophrenia, it is yet unclear however, if these patients exhibit this abnormal functional connectivity in the context of social-affective experiences. The current fMRI study, investigated functional connectivity dynamics within ToM and ES networks as subjects experienced evolving cinematic portrayals of fear. During scanning, schizophrenia patients and healthy controls passively watched a cinematic scene in which a mother and her son face various threatening events. Participants then provided a continuous and retrospective report of their fear intensity during a second viewing outside the scanner. Using network cohesion index (NCI) analysis, we examined modulations of ES-related and ToM-related functional connectivity dynamics and their relation to symptom severity and the continuous emotional ratings of the induced cinematic fear. Compared to patients, healthy controls showed higher ES-NCI and marginally lower ToM-NCI during emotional peaks. Cross-correlation analysis revealed an intriguing dynamic between NCI and the inter-group difference of reported fear. Schizophrenia patients rated their fear as lower relative to healthy controls, shortly after exhibiting lower ES connectivity. This increased difference in rating was also followed by higher ToM connectivity among schizophrenia patients. The clinical relevance of these findings is further highlighted by the following two results: (a) ToM-NCI was found to have a strong correlation with the severity of general symptoms during one of the two main emotional peaks (Spearman R?=?0.77); and (b) k-mean clustering demonstrated that the networks' NCI dynamic during the social-affective context reliably differentiated between patients and controls. Together, these findings point to a possible neural marker for abnormal social-affective processing in schizophrenia, manifested as the disturbed balance between two functional networks involved in social-affective affiliation. This in turn suggests that exaggerated mentalization over somatic-affiliative processing, in response to another's' distress may underlie social-affective deficits in schizophrenia.

SUBMITTER: Hendler T

PROVIDER: S-EPMC5802465 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Social affective context reveals altered network dynamics in schizophrenia patients.

Hendler Talma T Raz Gal G Shimrit Solnik S Jacob Yael Y Lin Tamar T Roseman Leor L Wahid Wahid Madah WM Kremer Ilana I Kupchik Marina M Kotler Moshe M Bleich-Cohen Maya M

Translational psychiatry 20180131 1

Impairments in social cognition and interactions are core psychopathologies in schizophrenia, often manifesting as an inability to appropriately relate to the intentions and feelings of others. Neuroimaging has helped to demarcate the dynamics of two distinct functional connectivity circuits underlying the social-affective processes related to mentalization (known as Theory of Mind, ToM) and somatic-affiliation (known as Embodied Simulation, ES). While evidence points to abnormal activation patt ...[more]

PMID: 29382814

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Project description:OBJECTIVE:Changes in heart rate (HR) and locomotor activity reflect changes in autonomic physiology, behavior, and mood. These systems may involve interrelated neural circuits that are altered in psychiatric illness, yet their interactions are poorly understood. We hypothesized interactions between HR and locomotor activity could be used to discriminate patients with schizophrenia from controls, and would be less able to discriminate non-psychiatric patients from controls. APPROACH:HR and locomotor activity were recorded via wearable patches in 16 patients with schizophrenia and 19 healthy controls. Measures of signal complexity and interactions were calculated over multiple time scales, including sample entropy, mutual information, and transfer entropy. A support vector machine was trained on these features to discriminate patients from controls. Additionally, time series were converted into a network with nodes comprised of HR and locomotor activity states, and edges representing state transitions. Graph properties were used as features. Leave-one-out cross validation was performed. To compare against non-psychiatric illness, the same approach was repeated in 41 patients with atrial fibrillation (AFib) and 53 controls. MAIN RESULTS:Network features enabled perfect discrimination of schizophrenia patients from controls with an areas under the receiver operating characteristic curve (AUC) of 1.00 for training and test data. Other bivariate measures of interaction achieved lower AUCs (train 0.98, test 0.96), and univariate measures of complexity achieved the lowest performance. Conversely, interaction features did not improve discrimination of AFib patients from controls beyond univariate approaches. SIGNIFICANCE:Interactions between HR and locomotor activity enabled perfect discrimination of subjects with schizophrenia from controls, but these features were less performant in a non-psychiatric illness. This is the first quantitative evaluation of interactions between physiology and behavior in patients with psychiatric illness.

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.

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Social affective context reveals altered network dynamics in schizophrenia patients.

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Social affective context reveals altered network dynamics in schizophrenia patients.

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