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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
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
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).
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)
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
.
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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).
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Schizophrenia: an integrated sociodevelopmental-cognitive model.
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[2] Owen MJ, Sawa A, Mortensen PB.
Schizophrenia.
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[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.
End of this article