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    Home > Active Ingredient News > Study of Nervous System > Transl Psychiatry—Yang Xun's team reveals the different neural mechanisms of schizophrenia in the reward expectation and reward outcome stages

    Transl Psychiatry—Yang Xun's team reveals the different neural mechanisms of schizophrenia in the reward expectation and reward outcome stages

    • Last Update: 2022-10-25
    • Source: Internet
    • Author: User
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    Written by Yan Jiangnan, edited by Yang Xun - Wang Sizhen, Fang Yiyi

    Editor—Summer Leaf


    Schizophrenia (SZ) is a serious neuropsychiatric disorder characterized by delusions, hallucinations, and thought disturbances [1,2].

    Patients with SZ exhibit abnormalities in reinforcement learning and reward processing, suggesting impairment in their reward decision-making system [3].

    There is increasing evidence that
    defects in reward handling in SZ patients may stem from the cortico-limbic system-striatum circuit (mesocorticolimbic).
    circuitry
    ), including dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex ( orbital prefrontal cortex (OFC), medial prefrontal cortex (mPFC).
    ), anterior cingulate cortex (ACC), ventral striatum (VS ), ventral pallidum, amygdala, hippocampus and thalamus


    According to the study, reward processing can be divided into two stages, namely the reward expectation stage and the reward result stage [4].

    And the neural matrix behind the two phases may be associated with
    different activation and functional connectivity patterns.
    The monetary incentive delay (MID) task is the most widely used task
    to explore the neural matrix of different stages of reward processing in healthy individuals and patients with mental disorders.
    To date, based on
    the MID task, studies have explored and identified possible neural substrates for the expected and outcome stages of reward processing [5].

    However, due to bias due to heterogeneity of samples and heterogeneity of tasks, the results of the available studies are inconsistent, especially the neural matrix behind the different stages of reward treatment and its correlation with disease symptoms is not fully understood
    .


    On October 16, 2022, Yang Xun's team from the School of Public Administration of Chongqing University delivered a presentation at Translational Psychiatry "Neural substrates of reward anticipation and outcome in schizophrenia: a meta-analysis of fMRI findings in the monetary incentive delay task
    ".
    In this study, the authors found that
    patients with SZ exhibited insufficient activation in the cortical-limbic-striatum circuit compared with healthy controls during the reward-expectancy phase, and that striatum activation was negatively associated with negative symptoms, Positively correlated with the proportion of patients taking second-generation antipsychotic (SGA); In the reward outcome phase, SZ patients showed overactivation in the striatal-limbic circuitry compared to the control group, in DLPFC and insufficient activation in mPFC, and activation of mPFC is negatively correlated
    with positive symptoms.
    Further moderation analysis showed that medication conditioning modulated the relationship between
    symptom severity and brain activity in the expected and outcome stages.
    In this paper
    , the neural substrates of different reward stages in SZ were identified, which helped explain the neuropathological mechanisms
    of potential reward processing defects in diseases.



    To elucidate the neurobiological basis of SZ at different stages of reward processing, the authors used SDM (seed-based d mapping, version 5.
    15
    ).
    style="font-size: 15px;color: black;background: white;font-family: ;" _istranslated="1">) Coordinates-based meta-analysis was performed to explore the role of SZ patients and healthy controls (HCs).
    Differences in
    brain region activation in the expected and outcome phases of MID tasks.
    First, two authors independently searched
    PubMed from January 2000 to May 2021.
    Related articles in the Web of Science and ScienceDirect databases, searched using the following keywords: 1) "schizophrenia" or "schizophrenic" or "schizoaffective" or "psychoses" or "psychosis" or "psychotic" or "first episode psychosis" or "FEP", 2).
    "functional magnetic resonance imaging" or "fMRI" or "neuroimaging", and 3) "monetary incentive delay task" or "MID"
    .
    Studies that met the following criteria would be included:
    1) Participants in studies were enrolled according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Statistical Classification of Diseases and Related Health Problems ( International Statistical Classification of Diseases and Related Health Problems (ICD) Diagnostic criteria for adult patients diagnosed with schizophrenia, schizoaffective disorder, or other psychotic spectrum disorders (age>18 years); 2) studies compared differences in whole-brain functional activation between SZ patients and HC; 3) Research the use of classic MID tasks or modified MID tasks; 4) study the use of fMRI to study neural activity; 5) The report reported the functional activation of brain regions in the expected stage or outcome stage of the MID task; and 6) studies were reported in Talairach Atlas (Tal) or the Montreal Neurological Institute ( MNI) 3D coordinate results
    in space.
    Finally, a total
    of 17 studies were included in the meta-analysis of the reward expectation phase and 10 studies in the meta-analysis of the reward outcome stage.


    1.
    Reward the anticipatory phase

    In the meta-analysis of reward expectations, SZ was found in the striatum (extending to the insula and amygdala), the ACC, the middle cingulate cortex (MCC), the right central anterior gyrus, and the right superior temporal gyrus (STG) relative to healthy controls ) shows lower activation (Figure 1).

    Further, the authors used the Positive and Negative Syndrome Scale-Negative (PANSS-N) scores on the Positive and Negative Syndrome Scale as a measure of the severity of negative symptoms.
    Regression analysis and moderation analysis were performed using the proportion of patients in the patient group who had taken second-generation antipsychotics (
    % of SGA users) as a measure of the degree of medication.

    The results showed that
    PANSS-N was negatively correlated
    with low VS activation induced by reward expectations.
    In addition, medication
    modulates the relationship between the severity of negative symptoms and VS activity
    .
    That is to say, in the case of low degree of medication, the negative symptoms of patients are negatively correlated with striatum activation, while in the case of higher degree of medication, the correlation between negative symptoms and striatum activation is not significant (Figure 2).


    2.
    Reward the result stage

    In the meta-analysis of reward outcomes, SZ showed higher activation in bilateral striatum (extending to bilateral insula, amygdala, and hippocampus), left cerebellum, right parahippocampal gyrus, right posterior central gyrus, and right MCC relative to healthy controls; Exhibits lower activation in mPFC and DLPFC (Figure 1).

    Regression analysis showed that the severity of positive symptoms (PANSS-Positive, PANSS-P) was negatively correlated with low activation of mPFC induced by reward feedback
    In addition, the results of the modulation analysis showed that the drug also played a moderating role in the relationship between positive symptoms and mPFC activation (Figure 2).


    Fig.
    1 Activation difference between SZ and HC during reward expectation (A) and reward result (B).

    (Source: J.
    Zeng
    , et al.
    , Transll Psychiatry,
    2022).


    Fig.
    2 Correlation and regulation analysis between clinical symptoms and brain activation during reward expectations (A-C) and reward outcomes (D-F).

    (Source: J.
    Zeng
    , et al.
    , Transll Psychiatry,
    2022).


    In summary, the study reveals the neural mechanisms of different stages of reward processing in patients with schizophrenia (SZ) and their correlation
    with clinical symptoms.
    Patients with SZ exhibit insufficient activation of the mid-cortical limbic circuit during the reward-expectancy phase; Increased activation in the striatum-marginal circuit, as well as decreased activation
    in the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC
    。 Among them, insufficient activation of the ventral striatum (
    VS) induced by reward expectation was associated with negative symptoms, and mPFC activation induced by reward feedback was associated
    with positive symptoms.
    The findings show isolated neurobiological mechanisms at different stages of reward processing, helping to elucidate
    complex brain-behavioral relationships in SZ patients, and potentially revealing biomarkers that can be used to predict therapeutic disease
    .
    On the downside, due to the heterogeneity of brain activity in the reward-expecting phase due to differences in medication history or disease stage in the included samples, future longitudinal studies are needed to further validate the effects of
    drugs and disease stages on neurological dysfunction in reward processing.
    In addition, the results of regression and conditioning analyses, while statistically significant, are preliminary explorations, and the relationship between symptoms and the brain is so complex that further validation
    of how this relationship changes with regulation of antipsychotic therapy is needed in controlled clinical trials.

    Original link: https://doi.
    org/10.
    1038/s41398-022-02201-8


    Yang Xun, associate professor of the School of Public Administration of Chongqing University, is the corresponding author of the paper, and Zeng Jianguang, professor of the School of Economics and Business Administration of Chongqing University, Yan Jiangnan, a doctoral student of the School of Economics and Business Administration of Chongqing University, and Cao Hengyi, assistant professor of psychiatry at the Feinstein Institute of Medical Research, are the co-first authors
    of the paper.
    This work was supported by the National Natural Science Foundation of China (
    31700964); The Fundamental Research Fund of Central Universities (2020CDJSK01XK02) and other projects are supported
    .


    Corresponding author: Yang Xun

    (Photo courtesy of Yang Xun's team)


    Corresponding author bio (swipe up and down to read).

    Xun Yang, Ph.
    D.
    , associate professor, master supervisor, psychotherapist
    .
    He has an interdisciplinary background in management, psychology and cognitive neuroscience, and holds a master's degree in psychology and a doctorate in
    medicine.
    He has long been engaged in teaching and research in the fields of decision psychology, health economics and public health and public administration
    .
    His main research interests are cutting-edge interdisciplinary research in
    economic decision-making and brain science, and explore the cognitive decision-making patterns and physiological mechanisms
    of normal people and people with mental disorders by combining the research paradigm of psychology and decision-making modeling of economic management with multimodal MRI imaging.
    He has presided over and participated in a number of national, provincial and ministerial projects, including the National Natural Science Foundation of China, the National Postdoctoral Program, etc.
    , and has published
    more than 30 SCI papers, including the first author or corresponding author in Neuroscience and Biobehavioral Reviews , NeuroImage, Ebiomedcine, SCAN and other international first-class journals published SCI papers10 The remaining papers, of which 1 was selected as a highly cited ESI paper, and 3 were SCI with an impact factor of 8 points or higher Dissertation, with a total impact factor of more than 50
    .
    The relevant research has received invitations from top international conferences, such as
    ISMRM, HBM, etc.
    , to do oral and poster exchanges, and has been
    awarded the ISMRM Magna Laude Merit by ISMRM Award for
    Outstanding Paper.


    The research team mainly adopts psychology, economics, cognitive neuroscience and other multidisciplinary methods to study the psychological phenomenon of decision-making, and welcomes students who are interested in decision-making psychology
    .
    Teacher Yang Xun's email:
    yangxunjg@163.
    com

    .


    A selection of past articles

    [1] Schizophrenia—Brain network hub and working memory performance in patients with schizophrenia

    [2] Front Cell Neurosci—uses bibliometrics to analyze research trends in astrocytes and stroke

    [3] Cereb Cortex-Liu Tao's team revealed the accelerated degeneration pattern of white matter structure in the elderly

    [4] Biophys J—Professor Xu Guangkui's research group reveals the network dynamics of nonlinear power-law relaxation in the cell cortex

    [5] Science—Analysis of neurogenesis and regeneration in Mexican salamander using single-cellular, multi-omics techniques

    [6] J Neuroinflammation Review—Ni Wenfei/Zhou Kailiang team focused on the important role of STING pathway in neuroinflammation and cell death after CNS injury

    [7] Sci Adv—Sheng Neng-yin/Mao Bingyu/Ding Yuqiang teamed up to discover a new mechanism of AMPA receptor ubiquitination in the regulation of excitatory synaptic function

    [8] Brain—Liu Gang/Hu Qingmao's team revealed the driving role of auxiliary motor areas in the alteration of the whole brain structural network in patients with blepharospasm

    [9] FASEB J—Liu Yang's team found that antipsychotic drugs on experimental animals caused vascular abnormalities in hematopoietic organs

    [10] Science-Du Yang team and others collaborated to develop non-opioid-free analgesics that target adrenergic receptors

    Recommended high-quality scientific research training courses[1] Symposium on Single Cell Sequencing and Spatial Transcriptomics Data Analysis (October 29-30 Tencent Online Conference) Conference/Forum/Seminar Preview

    [1] Immune Zoom Seminar—Screening of B cells in the immune and nervous system (Professor Xu Heping)

    [2] Academic Conference - 2022 Symposium on Neural Circuit Tracing Technology and the Second Round of the Second Round of the 6th National Training Course on Neural Circuit Tracing Technology

    Welcome to "Logical Neuroscience"[1]" "Logical Neuroscience" Editor/Operation Position ( Online Office)[2] Talent Recruitment - " Logical Neuroscience " Recruitment Article Interpretation/Writing Position ( Internet Part-time, Online Office)
    Reference (Swipe up and down to read).


    [1] Howes OD, Murray RM.
    Schizophrenia: an integrated sociodevelopmental-cognitive model.
    Lancet 2014; 383:1677-1687.

    [2] Owen MJ, Sawa A, Mortensen PB.
    Schizophrenia.
    Lancet 2016; 388:86-97.

    [3] Chang WC, Waltz JA, Gold JM, Chan TCW, Chen EYH.
    Mild Reinforcement Learning Deficits in Patients With First-Episode Psychosis.
    Schizophrenia Bull 2016; 42:1476-1485.

    [4] Knutson B, Fong GW, Adams CM, Varner JL, Hommer D.
    Dissociation of reward anticipation and outcome with event-related fMRI.
    Neuroreport 2001; 12:3683-3687.

    [5] Radua J, Schmidt A, Borgwardt S, Heinz A, Schlagenhauf F, McGuire P, et al.
    Ventral Striatal Activation During Reward Processing in Psychosis: A Neurofunctional Meta-Analysis.
    JAMA Psychiatry 2015; 72:1243-1251.



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