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Mewton P, Dawel A, Miller EJ, Shou Y, Christensen BK. Meta-analysis of Face Perception in Schizophrenia Spectrum Disorders: Evidence for Differential Impairment in Emotion Face Perception. Schizophr Bull 2024; 51:17-36. [PMID: 39136259 PMCID: PMC11661959 DOI: 10.1093/schbul/sbae130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2024]
Abstract
BACKGROUND AND HYPOTHESIS Schizophrenia spectrum disorders (SSD) are associated with face perception impairments. It is unclear whether impairments are equal across aspects of face perception or larger-indicating a differential impairment-for perceiving emotions relative to other characteristics (eg, identity, age). While many studies have attempted to compare emotion and non-emotion face perception in SSD, they have varied in design and produced conflicting findings. Additionally, prior meta-analyses on this topic were not designed to disentangle differential emotion impairments from broader impairments in face perception or cognition. We hypothesize that SSD-related impairments are larger for emotion than non-emotion face perception, but study characteristics moderate this differential impairment. STUDY DESIGN We meta-analyzed 313 effect sizes from 104 articles to investigate if SSD-related impairments are significantly greater for emotion than non-emotion face perception. We tested whether key study characteristics moderated these impairments, including SSD severity, sample intelligence matching, task difficulty, and task memory dependency. STUDY RESULTS We found significantly greater impairments for emotion (Cohen's d = 0.74) than non-emotion face perception (d = 0.55) in SSD relative to control samples, regardless of SSD severity, intelligence matching, or task difficulty. Importantly, this effect was obscured when non-emotion tasks used a memory-dependent design. CONCLUSIONS This is the first meta-analysis to demonstrate a differential emotion impairment in SSD that cannot be explained by broader impairments in face perception or cognition. The findings also underscore the critical role of task matching in studies of face perception impairments; to prevent confounding influences from memory-dependent task designs.
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Affiliation(s)
- Paige Mewton
- School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Canberra, Australia
| | - Amy Dawel
- School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Canberra, Australia
| | - Elizabeth J Miller
- School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Canberra, Australia
| | - Yiyun Shou
- School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Canberra, Australia
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
- Lloyd’s Register Foundation Institute for the Public Understanding of Risk, National University of Singapore, Singapore
| | - Bruce K Christensen
- School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Canberra, Australia
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Buck Z, Michalchyshyn E, Nishat A, Lisi M, Huang Y, Liu H, Makarenka A, Plyngam CP, Windle A, Yang Z, Walther DB. Aesthetic processing in neurodiverse populations. Neurosci Biobehav Rev 2024; 166:105878. [PMID: 39260715 DOI: 10.1016/j.neubiorev.2024.105878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 08/07/2024] [Accepted: 09/05/2024] [Indexed: 09/13/2024]
Abstract
Neurodiversity is a perspective on cognition which suggests a non-pathological view of individual cognitive differences. Aesthetics research on neurodivergent brains has generally been limited to neuropsychological cases. Although this research has been integral to establishing the neurological correlates of aesthetic experience, it is crucial to expand this paradigm to more psychologically complex disorders. We offer a review of research on aesthetic preference in neurodivergent brains beyond neuropsychological cases: across populations with psychotic disorder, anhedonia and depression, anxiety disorder, and autism. We identify stable patterns of aesthetic bias in these populations, relate these biases to symptoms at perceptual, emotional, and evaluative levels of cognition, review relevant neurological correlates, and connect this evidence to current neuroaesthetics theory. Critically, we synthesize the reviewed evidence and discuss its relevance for three brain networks regularly implicated in aesthetic processing: the mesocorticolimbic reward circuit, frontolimbic connections, and the default mode network. Finally, we propose that broadening the subject populations for neuroaesthetics research to include neurodiverse populations is instrumental for yielding new insights into aesthetic processing in the brain.
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Affiliation(s)
- Zach Buck
- Department of Psychology, University of Toronto, Toronto, Canada
| | | | - Amna Nishat
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Mikayla Lisi
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Yichen Huang
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Hanyu Liu
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Arina Makarenka
- Department of Psychology, University of Toronto, Toronto, Canada
| | | | - Abigail Windle
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Zhen Yang
- Department of Psychology, University of Toronto, Toronto, Canada
| | - Dirk B Walther
- Department of Psychology, University of Toronto, Toronto, Canada.
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Parisi M, Marin L, Fauviaux T, Aigoin E, Raffard S. Emotional Contagion and Emotional Mimicry in Individuals with Schizophrenia: A Systematic Review. J Clin Med 2024; 13:5296. [PMID: 39274509 PMCID: PMC11395795 DOI: 10.3390/jcm13175296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/31/2024] [Accepted: 09/03/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Individuals with schizophrenia often exhibit social interaction deficits, which can affect their ability to engage effectively with others. Emotional processes, such as emotional contagion (the transfer of emotion between individuals) and emotional mimicry (the imitation of emotional expressions), are crucial for enhancing the quality of social interactions. Methods: We conducted a PubMed, Web of Science, and PsycInfo database search. The inclusion and exclusion criteria were established based on the definitions of emotional contagion and emotional mimicry, rather than relying on specific terminology from various research fields. Forty-two studies were included in the review, including six emotional mimicry studies and thirty-six emotional contagion studies. Results: The current findings suggest decreased or inappropriate emotional mimicry in individuals with schizophrenia. Relating to emotional contagion, the results showed altered brain and psychophysiological activity in individuals with schizophrenia, whereas the self-reported measures indicated no difference between the groups. The relationships between emotional contagion, emotional mimicry, and psychotic symptom severity showed variability across the studies, whereas no associations between antipsychotic dosage and either emotional mimicry or emotional contagion were found. Discussion: This review highlights the need to further evaluate and train emotional contagion and emotional mimicry in individuals with schizophrenia because these processess influence social interaction quality. Clinical implications and guidelines for future studies are discussed.
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Affiliation(s)
- Mathilde Parisi
- EuroMov Digital Health in Motion, University of Montpellier, IMT Mines Ales Montpellier, 700 Avenue du Pic Saint Loup, 34090 Montpellier, France
| | - Ludovic Marin
- EuroMov Digital Health in Motion, University of Montpellier, IMT Mines Ales Montpellier, 700 Avenue du Pic Saint Loup, 34090 Montpellier, France
| | - Tifenn Fauviaux
- EuroMov Digital Health in Motion, University of Montpellier, IMT Mines Ales Montpellier, 700 Avenue du Pic Saint Loup, 34090 Montpellier, France
| | - Emilie Aigoin
- EuroMov Digital Health in Motion, University of Montpellier, IMT Mines Ales Montpellier, 700 Avenue du Pic Saint Loup, 34090 Montpellier, France
| | - Stéphane Raffard
- Faculty of Psychology, Univ Paul Valéry Montpellier 3, Univ. Montpellier, Laboratory EPSYLON EA 4556, 34090 Montpellier, France
- University Department of Adult Psychiatry, CHU Montpellier, 34000 Montpellier, France
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Liang L, Li S, Huang Y, Zhou J, Xiong D, Li S, Li H, Zhu B, Li X, Ning Y, Hou X, Wu F, Wu K. Relationships among the gut microbiome, brain networks, and symptom severity in schizophrenia patients: A mediation analysis. Neuroimage Clin 2024; 41:103567. [PMID: 38271852 PMCID: PMC10835015 DOI: 10.1016/j.nicl.2024.103567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 01/12/2024] [Accepted: 01/12/2024] [Indexed: 01/27/2024]
Abstract
The microbiome-gut-brain axis (MGBA) plays a critical role in schizophrenia (SZ). However, the underlying mechanisms of the interactions among the gut microbiome, brain networks, and symptom severity in SZ patients remain largely unknown. Fecal samples, structural and functional magnetic resonance imaging (MRI) data, and Positive and Negative Syndrome Scale (PANSS) scores were collected from 38 SZ patients and 38 normal controls, respectively. The data of 16S rRNA gene sequencing were used to analyze the abundance of gut microbiome and the analysis of human brain networks was applied to compute the nodal properties of 90 brain regions. A total of 1,691,280 mediation models were constructed based on 261 gut bacterial, 810 nodal properties, and 4 PANSS scores in SZ patients. A strong correlation between the gut microbiome and brain networks (r = 0.89, false discovery rate (FDR) -corrected p < 0.05) was identified. Importantly, the PANSS scores were linearly correlated with both the gut microbiome (r = 0.5, FDR-corrected p < 0.05) and brain networks (r = 0.59, FDR-corrected p < 0.05). The abundance of genus Sellimonas significantly affected the PANSS negative scores of SZ patients via the betweenness centrality of white matter networks in the inferior frontal gyrus and amygdala. Moreover, 19 significant mediation models demonstrated that the nodal properties of 7 brain regions, predominately from the systems of visual, language, and control of action, showed significant mediating effects on the PANSS scores with the gut microbiome as mediators. Together, our findings indicated the tripartite relationships among the gut microbiome, brain networks, and PANSS scores and suggested their potential role in the neuropathology of SZ.
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Affiliation(s)
- Liqin Liang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China
| | - Shijia Li
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Amsterdam, The Netherlands
| | - Yuanyuan Huang
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
| | - Jing Zhou
- School of Material Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
| | - Dongsheng Xiong
- School of Material Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
| | - Shaochuan Li
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China; Realmeta Technology (Guangzhou) Co., Ltd, Guangzhou 510535, China
| | - Hehua Li
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
| | - Baoyuan Zhu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China
| | - Xiaobo Li
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA
| | - Yuping Ning
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
| | - Xiaohui Hou
- Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou 510500, China.
| | - Fengchun Wu
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China.
| | - Kai Wu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
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Fleury M, Figueiredo P, Vourvopoulos A, Lécuyer A. Two is better? combining EEG and fMRI for BCI and neurofeedback: a systematic review. J Neural Eng 2023; 20:051003. [PMID: 37879343 DOI: 10.1088/1741-2552/ad06e1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 10/25/2023] [Indexed: 10/27/2023]
Abstract
Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are two commonly used non-invasive techniques for measuring brain activity in neuroscience and brain-computer interfaces (BCI).Objective. In this review, we focus on the use of EEG and fMRI in neurofeedback (NF) and discuss the challenges of combining the two modalities to improve understanding of brain activity and achieve more effective clinical outcomes. Advanced technologies have been developed to simultaneously record EEG and fMRI signals to provide a better understanding of the relationship between the two modalities. However, the complexity of brain processes and the heterogeneous nature of EEG and fMRI present challenges in extracting useful information from the combined data.Approach. We will survey existing EEG-fMRI combinations and recent studies that exploit EEG-fMRI in NF, highlighting the experimental and technical challenges.Main results. We made a classification of the different combination of EEG-fMRI for NF, we provide a review of multimodal analysis methods for EEG-fMRI features. We also survey the current state of research on EEG-fMRI in the different existing NF paradigms. Finally, we also identify some of the remaining challenges in this field.Significance. By exploring EEG-fMRI combinations in NF, we are advancing our knowledge of brain function and its applications in clinical settings. As such, this review serves as a valuable resource for researchers, clinicians, and engineers working in the field of neural engineering and rehabilitation, highlighting the promising future of EEG-fMRI-based NF.
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Affiliation(s)
- Mathis Fleury
- Univ Rennes, Inria, CNRS, Inserm, Empenn ERL U1228 Rennes, France
- ISR-Lisboa/LARSyS and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Patrícia Figueiredo
- ISR-Lisboa/LARSyS and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Athanasios Vourvopoulos
- ISR-Lisboa/LARSyS and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
| | - Anatole Lécuyer
- Univ Rennes, Inria, CNRS, Inserm, Empenn ERL U1228 Rennes, France
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Qin Y, Kang J, Jiao Z, Wang Y, Wang J, Wang H, Feng J, Jin L, Wang F, Gong X. Polygenic risk for autism spectrum disorder affects left amygdala activity and negative emotion in schizophrenia. Transl Psychiatry 2020; 10:322. [PMID: 32958750 PMCID: PMC7506524 DOI: 10.1038/s41398-020-01001-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 09/02/2020] [Accepted: 09/07/2020] [Indexed: 12/27/2022] Open
Abstract
Although the diagnoses based on phenomenology have many practical advantages, accumulating evidence shows that schizophrenia and autism spectrum disorder (ASD) share some overlap in genetics and clinical presentation. It remains largely unknown how ASD-associated polygenetic risk contributes to the pathogenesis of schizophrenia. In the present study, we calculated high-resolution ASD polygenic risk scores (ASD PRSs) and selected optimal ten ASD PRS with minimal P values in the association analysis of PRSs, with schizophrenia to assess the effect of ASD PRS on brain neural activity in schizophrenia cases and controls. We found that amplitude of low-frequency fluctuation in left amygdala was positively associated with ASD PRSs in our cohort. Correlation analysis of ASD PRSs with facial emotion recognition test identified the negative correlation of ASD PRSs with negative emotions in schizophrenia cases and controls. Finally, functional enrichment analysis of PRS genes revealed that neural system function and development, as well as signal transduction, were mainly enriched in PRS genes. Our results provide empirical evidence that polygenic risk for ASD contributes to schizophrenia by the intermediate phenotypes of left amygdala function and emotion recognition. It provides a promising strategy to understand the relationship between phenotypes and genotypes shared in mental disorders.
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Affiliation(s)
- Yue Qin
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Jujiao Kang
- grid.8547.e0000 0001 0125 2443Shanghai Center for Mathematical Science, Fudan University, Shanghai, China
| | - Zeyu Jiao
- grid.8547.e0000 0001 0125 2443Shanghai Center for Mathematical Science, Fudan University, Shanghai, China
| | - Yi Wang
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Jiucun Wang
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443Human Phoneme Institute, Fudan University, Shanghai, China
| | - Hongyan Wang
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
| | - Jianfeng Feng
- grid.8547.e0000 0001 0125 2443Shanghai Center for Mathematical Science, Fudan University, Shanghai, China ,grid.8547.e0000 0001 0125 2443Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China ,grid.7372.10000 0000 8809 1613Department of Computer Science, University of Warwick, Coventry, CV4 7AL UK
| | - Li Jin
- grid.8547.e0000 0001 0125 2443State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Fei Wang
- grid.412636.4Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiaohong Gong
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
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Mendrek A, Jiménez J, Mancini-Marïe A, Fahim C, Stip E. Correlations between sadness-induced cerebral activations and schizophrenia symptoms: An fMRI study of sex differences. Eur Psychiatry 2020; 26:320-6. [DOI: 10.1016/j.eurpsy.2010.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2009] [Revised: 04/12/2010] [Accepted: 04/14/2010] [Indexed: 11/28/2022] Open
Abstract
AbstractBackgroundThe functional neuroimaging studies of emotion processing in schizophrenia have revealed variable results attributed partly to differential symptomatology and sex of tested patients. The aim of the present study was to investigate the relationship between cerebral activations during exposure to emotional material and schizophrenia symptoms in men versus women.MethodFifteen men and 10 women with schizophrenia, equivalent in terms of age, medication and experienced symptomatology, underwent functional MRI during viewing sad and neutral film excerpts. Data were analyzed using Statistical Parametric Mapping Software (SPM2).ResultsAcross all the patients there was a significant inverse relationship between negative symptoms and activations in the right prefrontal cortex during processing of sad versus neutral stimuli. In men, activations during sad versus neutral stimuli in the prefrontal, temporal and anterior cingulate cortex, as well as the caudate and cerebellum, were positively correlated with negative symptoms. In women, there were inverse correlations between positive symptoms and activations in the hippocampus, parietal and occipital cortex during the same condition.ConclusionPresent results confirmed association of prefrontal hypofunction with negative symptoms in schizophrenia. More interestingly, the results revealed a diametrically different pattern of symptom-correlated brain activity in men and women with schizophrenia, suggesting that the processing of sadness is mediated via neurophysiological mechanism related to negative symptoms in men and the mechanism related to positive symptoms in women.
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Lakhlifi M, Laprevote V, Schwan R, Schwitzer T. Free viewing exploration in schizophrenia: Review of evidence from laboratory settings to natural environment. Encephale 2020; 46:115-122. [PMID: 32057409 DOI: 10.1016/j.encep.2019.11.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 11/26/2019] [Accepted: 11/28/2019] [Indexed: 10/25/2022]
Abstract
Several studies have investigated visual processing impairment in schizophrenia. The literature on visual exploration has described restricted scanning in schizophrenia patients. This gaze behavior is characterized by increased fixation duration, a reduced scan path length and avoidance of salient features of the face with emotional content. The aim of this paper is to give an insight on the latest update on scan path deficit. Abnormal gaze exploration was replicated in various visual stimuli. This review describes gaze patterns with stimuli that imply minimal to high cognitive process: figures, objects, faces, and scenes. Interestingly, schizophrenia patients have shown cognitive flexibility by modulating gaze scanning when they are involved in an active assignment. We will also consider scanning abnormalities in real-life environment and discuss the potential therapeutic use of eye tracking in schizophrenia. The therapeutic application of eye tracking in schizophrenia is a young emerging field in psychiatry research. The recent remediation program is based on the reorientation of visual attention on the salient features of faces. For now, this program has shown encouraging results. Further studies are needed to explore behavior in real-world situations to complement laboratory measurements to move toward a full understanding of the mechanisms underlying atypical scanning in patients with schizophrenia.
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Affiliation(s)
- M Lakhlifi
- Pôle hospitalo-universitaire de psychiatrie d'adultes du Grand-Nancy, centre psychothérapique de Nancy, Laxou, France.
| | - V Laprevote
- Pôle hospitalo-universitaire de psychiatrie d'adultes du Grand-Nancy, centre psychothérapique de Nancy, Laxou, France; Inserm U1114, fédération de médecine translationnelle de Strasbourg, département de psychiatrie, centre hospitalier régional universitaire de Strasbourg, Strasbourg, France; Maison des addictions, CHRU de Nancy, Nancy, France
| | - R Schwan
- Pôle hospitalo-universitaire de psychiatrie d'adultes du Grand-Nancy, centre psychothérapique de Nancy, Laxou, France; Inserm U1114, fédération de médecine translationnelle de Strasbourg, département de psychiatrie, centre hospitalier régional universitaire de Strasbourg, Strasbourg, France; Maison des addictions, CHRU de Nancy, Nancy, France
| | - T Schwitzer
- Pôle hospitalo-universitaire de psychiatrie d'adultes du Grand-Nancy, centre psychothérapique de Nancy, Laxou, France; Inserm U1114, fédération de médecine translationnelle de Strasbourg, département de psychiatrie, centre hospitalier régional universitaire de Strasbourg, Strasbourg, France; Maison des addictions, CHRU de Nancy, Nancy, France
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DeCross SN, Farabaugh AH, Holmes AJ, Ward M, Boeke EA, Wolthusen RPF, Coombs G, Nyer M, Fava M, Buckner RL, Holt DJ. Increased amygdala-visual cortex connectivity in youth with persecutory ideation. Psychol Med 2020; 50:273-283. [PMID: 30744715 DOI: 10.1017/s0033291718004221] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis. METHODS A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured. RESULTS Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs. CONCLUSIONS These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.
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Affiliation(s)
- Stephanie N DeCross
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - Amy H Farabaugh
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Avram J Holmes
- Department of Psychology, Yale University, New Haven, CT, USA
| | - Maeve Ward
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Sidney Kimmel Medical College, Philadelphia, PA, USA
| | - Emily A Boeke
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychology, New York University, New York, NY, USA
| | - Rick P F Wolthusen
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Division of Psychological & Social Medicine and Developmental Neurosciences, Faculty of Medicine Carl Gustav Carus of the Technische Universität Dresden, Dresden, Germany
| | - Garth Coombs
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - Maren Nyer
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Maurizio Fava
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Randy L Buckner
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA
- Harvard Medical School, Boston, MA, USA
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - Daphne J Holt
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA
- Harvard Medical School, Boston, MA, USA
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10
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Yue JL, Li P, Shi L, Lin X, Sun HQ, Lu L. Enhanced temporal variability of amygdala-frontal functional connectivity in patients with schizophrenia. NEUROIMAGE-CLINICAL 2018; 18:527-532. [PMID: 29560309 PMCID: PMC5857898 DOI: 10.1016/j.nicl.2018.02.025] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 01/27/2018] [Accepted: 02/26/2018] [Indexed: 12/19/2022]
Abstract
Background The “dysconnectivity hypothesis” was proposed 20 years ago. It characterized schizophrenia as a disorder with dysfunctional connectivity across a large range of distributed brain areas. Resting-state functional magnetic resonance imaging (rsfMRI) data have supported this theory. Previous studies revealed that the amygdala might be responsible for the emotion regulation-related symptoms of schizophrenia. However, conventional methods oversimplified brain activities by assuming that it remained static throughout the entire scan duration, which may explain why inconsistent results have been reported for the same brain region. Methods An emerging technique is sliding time window analysis, which is used to describe functional connectivity based on the temporal variability of regions of interest (e.g., amygdala) in patients with schizophrenia. Conventional analysis of the static functional connectivity between the amygdala and whole brain was also conducted. Results Static functional connectivity between the amygdala and orbitofrontal region was impaired in patients with schizophrenia. The variability of connectivity between the amygdala and medial prefrontal cortex was enhanced (i.e., greater dynamics) in patients with schizophrenia. A negative relationship was found between the variability of connectivity and information processing efficiency. A positive correlation was found between the variability of connectivity and symptom severity. Conclusion The findings suggest that schizophrenia was related to abnormal patterns of fluctuating communication among brain areas that are involved in emotion regulations. Unveiling the temporal properties of functional connectivity could disentangle the inconsistent results of previous functional connectivity studies.
FC between the amygdala and orbitofrontal region is impaired in patients with SZ. The variability of FC between amygdala and MPFC was enhanced in patients with SZ. Positive correlation was found between the variability of FC and symptom severity.
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Affiliation(s)
- Jing-Li Yue
- Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
| | - Peng Li
- Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
| | - Le Shi
- National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China
| | - Xiao Lin
- Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
| | - Hong-Qiang Sun
- Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.
| | - Lin Lu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
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11
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Belge JB, Maurage P, Mangelinckx C, Leleux D, Delatte B, Constant E. Facial decoding in schizophrenia is underpinned by basic visual processing impairments. Psychiatry Res 2017; 255:167-172. [PMID: 28554121 DOI: 10.1016/j.psychres.2017.04.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 02/26/2017] [Accepted: 04/02/2017] [Indexed: 11/19/2022]
Abstract
Schizophrenia is associated with a strong deficit in the decoding of emotional facial expression (EFE). Nevertheless, it is still unclear whether this deficit is specific for emotions or due to a more general impairment for any type of facial processing. This study was designed to clarify this issue. Thirty patients suffering from schizophrenia and 30 matched healthy controls performed several tasks evaluating the recognition of both changeable (i.e. eyes orientation and emotions) and stable (i.e. gender, age) facial characteristics. Accuracy and reaction times were recorded. Schizophrenic patients presented a performance deficit (accuracy and reaction times) in the perception of both changeable and stable aspects of faces, without any specific deficit for emotional decoding. Our results demonstrate a generalized face recognition deficit in schizophrenic patients, probably caused by a perceptual deficit in basic visual processing. It seems that the deficit in the decoding of emotional facial expression (EFE) is not a specific deficit of emotion processing, but is at least partly related to a generalized perceptual deficit in lower-level perceptual processing, occurring before the stage of emotion processing, and underlying more complex cognitive dysfunctions. These findings should encourage future investigations to explore the neurophysiologic background of these generalized perceptual deficits, and stimulate a clinical approach focusing on more basic visual processing.
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Affiliation(s)
- Jan-Baptist Belge
- Department of Psychiatry, Saint-Luc University Hospital and Institute of Neuroscience (IoNS), Université catholique de Louvain, 10 Avenue Hippocrate, B-1200 Brussels, Belgium
| | - Pierre Maurage
- Laboratory for Experimental Psychopathology, Psychological Sciences Research Institute, Université Catholique de Louvain, 10 Place C. Mercier, B-1348 Louvain-la-Neuve, Belgium
| | - Camille Mangelinckx
- Laboratory for Experimental Psychopathology, Psychological Sciences Research Institute, Université Catholique de Louvain, 10 Place C. Mercier, B-1348 Louvain-la-Neuve, Belgium
| | - Dominique Leleux
- Psychiatric Hospital Sanatia, 27 Rue du Moulin, B-1210 Brussels, Belgium
| | - Benoît Delatte
- Beau Vallon Psychiatric Hospital, 205 Rue de Bricgniot, B- 5002 Namur, Belgium
| | - Eric Constant
- Department of Psychiatry, Saint-Luc University Hospital and Institute of Neuroscience (IoNS), Université catholique de Louvain, 10 Avenue Hippocrate, B-1200 Brussels, Belgium.
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12
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Sabharwal A, Kotov R, Szekely A, Leung HC, Barch DM, Mohanty A. Neural markers of emotional face perception across psychotic disorders and general population. JOURNAL OF ABNORMAL PSYCHOLOGY 2017; 126:663-678. [PMID: 28557508 PMCID: PMC5695570 DOI: 10.1037/abn0000279] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
There is considerable variation in negative and positive symptoms of psychosis, global functioning, and emotional face perception (EFP), not only in schizophrenia but also in other psychotic disorders and healthy individuals. However, EFP impairment and its association with worse symptoms and global functioning have been examined largely in the domain of schizophrenia. The present study adopted a dimensional approach to examine the association of behavioral and neural measures of EFP with symptoms of psychosis and global functioning across individuals with schizophrenia spectrum (SZ; N = 28) and other psychotic (OP; N = 29) disorders, and never-psychotic participants (NP; N = 21). Behavioral and functional MRI data were recorded as participants matched emotional expressions of faces and geometrical shapes. Lower accuracy and increased activity in early visual regions, hippocampus, and amygdala during emotion versus shape matching were associated with higher negative, but not positive, symptoms and lower global functioning, across all participants. This association remained even after controlling for group-related (SZ, OP, and NP) variance, dysphoria, and antipsychotic medication status, except in amygdala. Furthermore, negative symptoms mediated the relationship between behavioral and brain EFP measures and global functioning. This study provides some of the first evidence supporting the specific relationship of EFP measures with negative symptoms and global functioning across psychotic and never-psychotic samples, and transdiagnostically across different psychotic disorders. Present findings help bridge the gap between basic EFP-related neuroscience research and clinical research in psychosis, and highlight EFP as a potential symptom-specific marker that tracks global functioning. (PsycINFO Database Record
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Affiliation(s)
| | - Roman Kotov
- Department of Psychiatry, Stony Brook University
| | - Akos Szekely
- Department of Psychology, Stony Brook University
| | | | - Deanna M. Barch
- Departments of Psychology, Psychiatry, and Radiology, Washington University in St. Louis
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13
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Don’t worry, be happy - Neural correlates of the influence of musically induced mood on self-evaluation. Neuropsychologia 2017; 100:26-34. [DOI: 10.1016/j.neuropsychologia.2017.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2016] [Revised: 02/25/2017] [Accepted: 04/06/2017] [Indexed: 11/22/2022]
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14
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Garrett N, Lazzaro SC, Ariely D, Sharot T. The brain adapts to dishonesty. Nat Neurosci 2016; 19:1727-1732. [PMID: 27775721 PMCID: PMC5238933 DOI: 10.1038/nn.4426] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 09/27/2016] [Indexed: 11/09/2022]
Abstract
Dishonesty is an integral part of our social world, influencing domains ranging from finance and politics to personal relationships. Anecdotally, digressions from a moral code are often described as a series of small breaches that grow over time. Here we provide empirical evidence for a gradual escalation of self-serving dishonesty and reveal a neural mechanism supporting it. Behaviorally, we show that the extent to which participants engage in self-serving dishonesty increases with repetition. Using functional MRI, we show that signal reduction in the amygdala is sensitive to the history of dishonest behavior, consistent with adaptation. Critically, the extent of reduced amygdala sensitivity to dishonesty on a present decision relative to the previous one predicts the magnitude of escalation of self-serving dishonesty on the next decision. The findings uncover a biological mechanism that supports a 'slippery slope': what begins as small acts of dishonesty can escalate into larger transgressions.
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Affiliation(s)
- Neil Garrett
- Affective Brain Lab, Department of Experimental Psychology,
University College London, United Kingdom
| | - Stephanie C. Lazzaro
- Affective Brain Lab, Department of Experimental Psychology,
University College London, United Kingdom
| | - Dan Ariely
- Fuqua School of Business, Duke University, North Carolina, United
States of America
| | - Tali Sharot
- Affective Brain Lab, Department of Experimental Psychology,
University College London, United Kingdom
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15
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Haigh SM, Gupta A, Barb SM, Glass SAF, Minshew NJ, Dinstein I, Heeger DJ, Eack SM, Behrmann M. Differential sensory fMRI signatures in autism and schizophrenia: Analysis of amplitude and trial-to-trial variability. Schizophr Res 2016; 175:12-19. [PMID: 27083780 PMCID: PMC4958557 DOI: 10.1016/j.schres.2016.03.036] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 03/24/2016] [Accepted: 03/30/2016] [Indexed: 01/06/2023]
Abstract
Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (d<0.29). These differential group profiles suggest (1) that greater trial-to-trial variability in cortical responses may be specific to autism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders.
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Affiliation(s)
- Sarah M. Haigh
- Department of Psychology, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA.,Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Akshat Gupta
- Department of Psychology, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA
| | - Scott M. Barb
- School of Social Work, University of Pittsburgh, 2117 Cathedral of Learning, Pittsburgh, PA 15260, USA
| | - Summer A. F. Glass
- School of Social Work, University of Pittsburgh, 2117 Cathedral of Learning, Pittsburgh, PA 15260, USA
| | - Nancy J. Minshew
- Departments of Psychiatry & Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Ilan Dinstein
- Psychology Department, Ben-Gurion University of the Negev, 653, Beer-Sheva, 84105, Israel
| | - David J. Heeger
- Department of Psychology and Center for Neural Science, New York University, 6 Washington Place, New York, NY 10003, USA
| | - Shaun M. Eack
- School of Social Work, University of Pittsburgh, 2117 Cathedral of Learning, Pittsburgh, PA 15260, USA.,Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Marlene Behrmann
- Department of Psychology, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA
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16
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Lindner C, Dannlowski U, Bauer J, Ohrmann P, Lencer R, Zwitserlood P, Kugel H, Suslow T. Affective Flattening in Patients with Schizophrenia: Differential Association with Amygdala Response to Threat-Related Facial Expression under Automatic and Controlled Processing Conditions. Psychiatry Investig 2016; 13:102-11. [PMID: 26766952 PMCID: PMC4701673 DOI: 10.4306/pi.2016.13.1.102] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 04/14/2015] [Accepted: 05/07/2015] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE Early neuroimaging studies have demonstrated amygdala hypoactivation in schizophrenia but more recent research based on paradigms with minimal cognitive loads or examining automatic processing has observed amygdala hyperactivation. Hyperactivation was found to be related to affective flattening. In this study, amygdala responsivity to threat-related facial expression was investigated in patients as a function of automatic versus controlled processing and patients' flat affect. METHODS Functional magnetic resonance imaging was used to measure amygdala activation in 36 patients with schizophrenia and 42 healthy controls. During scanning, a viewing task with masked and unmasked fearful and neutral faces was presented. RESULTS Patients exhibited increased amygdala response to unmasked fearful faces. With respect to masked fearful faces, no between-group differences emerged for the sample as a whole but a subsample of patients with flat affect showed heightened amygdala activation. The amygdala response to masked fearful faces was positively correlated with the degree of flat affect. Conversely, amygdala response to unmasked fearful faces was negatively correlated to the severity of affective flattening. In patients, amygdala responses to masked and unmasked fearful faces showed an inverse correlation. CONCLUSION Our findings suggest that amygdala hyperresponsivity to unmasked fearful faces might be a functional characteristic of schizophrenia. Amygdala hyperresponsivity to masked fearful faces might be a specific characteristic of patients with affective flattening. A model of flat affect as a response mechanism to emotional overload is proposed.
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Affiliation(s)
- Christian Lindner
- Department of Psychosomatic Medicine, University of Leipzig, Leipzig, Germany
| | - Udo Dannlowski
- Department of Psychiatry, University of Münster, Münster, Germany
- Department of Psychiatry, University of Marburg, Marburg, Germany
| | - Jochen Bauer
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Patricia Ohrmann
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Rebekka Lencer
- Department of Psychiatry, University of Münster, Münster, Germany
| | | | - Harald Kugel
- Department of Clinical Radiology, University of Münster, Münster, Germany
| | - Thomas Suslow
- Department of Psychosomatic Medicine, University of Leipzig, Leipzig, Germany
- Department of Psychiatry, University of Münster, Münster, Germany
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17
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Maher S, Ekstrom T, Chen Y. Impaired visual cortical processing of affective facial information in schizophrenia. Clin Psychol Sci 2015; 4:651-660. [PMID: 27833789 DOI: 10.1177/2167702615609595] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Facial emotion perception impairment in schizophrenia is currently viewed as abnormal affective processing. Facial emotion perception also relies on visual processing. Yet, visual cortical processing of facial emotion is not well understood in this disorder. We measured perceptual thresholds for detecting facial fear and happiness in patients (n=23) and controls (n=23), and adjusted emotion intensity of facial stimuli (via morphing between images of neutral and emotive expressions) for each subject. We then evaluated activations of the visual cortex and amygdala during the performance of perceptually-equated facial emotion detection tasks. Patients had significantly lower fear- and happiness-induced activations in the visual cortex and amygdala. Activations between the visual cortex and amygdala were largely correlated, but the correlations in patients occurred abnormally early in response time course during fear perception. In schizophrenia, visual processing of facial emotion is deficient and visual and affective processing of negative facial emotion may be prematurely associated.
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Affiliation(s)
- S Maher
- McLean Hospital, Harvard Medical School
| | - T Ekstrom
- McLean Hospital, Harvard Medical School
| | - Y Chen
- McLean Hospital, Harvard Medical School
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18
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Rose A, Vinogradov S, Fisher M, Green MF, Ventura J, Hooker C, Merzenich M, Nahum M. Randomized controlled trial of computer-based treatment of social cognition in schizophrenia: the TRuSST trial protocol. BMC Psychiatry 2015; 15:142. [PMID: 26138715 PMCID: PMC4489025 DOI: 10.1186/s12888-015-0510-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 05/28/2015] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Schizophrenia is a severe and chronic medical condition, characterized by positive and negative symptoms, as well as pervasive social cognitive deficits. Despite the functional significance of the social cognition deficits affecting many aspects of daily living, such as social relationships, occupational status, and independent living, there is still no effective treatment option for these deficits, which is applied as standard of care. To address this need, we developed a novel, internet-based training program that targets social cognition deficits in schizophrenia (SocialVille). Preliminary studies demonstrate the feasibility and initial efficacy of Socialville in schizophrenia patients (Nahum et al., 2014). The purpose of the current trial (referred to as the TReatment of Social cognition in Schizophrenia Trial or TRuSST) is to compare SocialVille to an active control training condition, include a larger sample of patients, and assess both social cognitive functioning, and functional outcomes. METHODS/DESIGN We will employ a multi-site, longitudinal, blinded, randomized controlled trial (RCT) design with a target sample of 128 patients with schizophrenia. Patients will perform, at their home or in clinic, 40 sessions of either the SocialVille training program or an active control computer game condition. Each session will last for 40-45 minutes/day, performed 3-5 days a week, over 10-12 weeks, totaling to 30 hours of training. Patients will be assessed on a battery of social cognitive, social functioning and functional outcomes immediately before training, mid-way through training (after 20 training sessions) and at the completion of the 40 training sessions. DISCUSSION The strengths of this protocol are that it tests an innovative, internet-based treatment that targets fundamental social cognitive deficits in schizophrenia, employs a highly sensitive and extensive battery of functional outcome measures, and incorporates a large sample size in an RCT design. TRIAL REGISTRATION ClinicalTrials.gov NCT02246426 Registered 16 September 2014.
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Affiliation(s)
- Annika Rose
- Posit Science Corporation, 77 Geary Street, San Francisco, CA, 94108, USA.
| | - Sophia Vinogradov
- San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA, 94143, USA.
| | - Melissa Fisher
- San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA, 94143, USA.
| | - Michael F Green
- VA Greater Los Angeles, 11301 Wilshire Boulevard, Los Angeles, CA, 90073, USA.
| | - Joseph Ventura
- UCLA Aftercare Research Program, 760 Westwood Plaza, Los Angeles, CA, 90095, USA.
| | - Christine Hooker
- Department of Psychology, Harvard University, 1020 William James Hall 33 Kirkland St., Cambridge, MA, 02138, USA.
| | - Michael Merzenich
- Posit Science Corporation, 77 Geary Street, San Francisco, CA, 94108, USA.
| | - Mor Nahum
- Posit Science Corporation, 77 Geary Street, San Francisco, CA, 94108, USA.
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19
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Goldstein JM, Lancaster K, Longenecker JM, Abbs B, Holsen LM, Cherkerzian S, Whitfield-Gabrieli S, Makris N, Tsuang MT, Buka SL, Seidman LJ, Klibanski A. Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses. Psychiatry Res 2015; 232:226-36. [PMID: 25914141 PMCID: PMC4439265 DOI: 10.1016/j.pscychresns.2015.03.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Revised: 02/05/2015] [Accepted: 03/23/2015] [Indexed: 11/20/2022]
Abstract
Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.
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Affiliation(s)
- Jill M Goldstein
- Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA; Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
| | - Katie Lancaster
- Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA.
| | - Julia M Longenecker
- Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA.
| | - Brandon Abbs
- Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA.
| | - Laura M Holsen
- Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA; Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
| | - Sara Cherkerzian
- Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA.
| | - Susan Whitfield-Gabrieli
- Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
| | - Nicolas Makris
- Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
| | - Ming T Tsuang
- Center for Behavior Genomics, Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
| | - Stephen L Buka
- Department of Community Health, Brown University, Providence, RI, USA.
| | - Larry J Seidman
- Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Division of Public Psychiatry, Massachusetts Mental Health Center and Harvard Medical School, Boston, MA, USA.
| | - Anne Klibanski
- Department of Medicine, Harvard Medical School, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
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20
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Abstract
Ketamine can induce a transient psychosis via its influence on ionotropic N-methyl-d-aspartate receptors. Unlike dopamine agonists, which specifically mimic the positive symptoms seen in psychotic illnesses such as schizophrenia, ketamine may provide a better model because it is able to induce not only positive symptoms but also schizophrenia-like cognitive and negative symptoms. To test the veracity of the ketamine model further, research is attempting to replicate a range of cognitive deficits associated with schizophrenia in healthy controls under the influence of ketamine. Facial processing is one area that is impaired in schizophrenia. More specifically, research suggests that schizophrenia is associated with a reduced facial inversion effect reflecting abnormalities in configural face processing. The purpose of the current study was to determine whether ketamine would also reduce the facial inversion effect. This study was a double-blind, placebo-controlled repeated-measures design in which data are presented for 14 participants who received ketamine on one occasion and saline on another. The results supported the ketamine model, with the participants demonstrating an intact inversion effect in the placebo condition but no inversion effect under the influence of ketamine. Further, participants' self-reported deficits in visual processing correlated with their inversion score and errors on the faces task. Future studies should examine a wider range of facial processing tasks with a larger sample to confirm the current results and to determine the specificity of ketamine's ability to mimic schizophrenia facial processing deficits. The current study is supportive of the role of glutamate system in the processing of configural face information.
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21
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Pallanti S, Salerno L. Raising attention to attention deficit hyperactivity disorder in schizophrenia. World J Psychiatry 2015; 5:47-55. [PMID: 25815254 PMCID: PMC4369549 DOI: 10.5498/wjp.v5.i1.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 11/20/2014] [Accepted: 12/31/2014] [Indexed: 02/05/2023] Open
Abstract
Schizophrenia and attention deficit hyperactivity disorder (ADHD) are two psychiatric disorders with a negative impact on quality of life of individuals affected. Although they are classified into distinct disorders categories, attentional dysfunction is considered as a core feature in both conditions, either at the clinical then pathophysiological level. Beyond the obvious clinical overlap between these disorders, the Research Domain Criteria approach might offer an interesting perspective for disentangling common circuits underpinning both disorders. Hence, we review evidences regarding the overlap between schizophrenia and ADHD, at the clinical level, and at the level of underlying brain mechanisms. The evidence regarding the influence of environmental risk factors in the emergence of both disorders, and their developmental trajectories is also reviewed. Among these, we will try to elucidate the complex relationship between stimulants use and psychotic symptoms, discussing the potential role of ADHD medication in inducing psychosis or in exacerbating it. We aim that, taken together, these findings may promote further investigation with important implications both for clinicians and research. In fact, considering the amounting evidence on the overlap between schizophrenia and ADHD, the delineation of their boundaries might help in the decision for diagnosis and treatment. Moreover, it may help to promote interventions focused on the prevention of both schizophrenia and ADHD, by the reduction of recognized environmental risk factors.
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22
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Bortolon C, Capdevielle D, Raffard S. Face recognition in schizophrenia disorder: A comprehensive review of behavioral, neuroimaging and neurophysiological studies. Neurosci Biobehav Rev 2015; 53:79-107. [PMID: 25800172 DOI: 10.1016/j.neubiorev.2015.03.006] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 02/11/2015] [Accepted: 03/12/2015] [Indexed: 12/20/2022]
Abstract
Facial emotion processing has been extensively studied in schizophrenia patients while general face processing has received less attention. The already published reviews do not address the current scientific literature in a complete manner. Therefore, here we tried to answer some questions that remain to be clarified, particularly: are the non-emotional aspects of facial processing in fact impaired in schizophrenia patients? At the behavioral level, our key conclusions are that visual perception deficit in schizophrenia patients: are not specific to faces; are most often present when the cognitive (e.g. attention) and perceptual demands of the tasks are important; and seems to worsen with the illness chronification. Although, currently evidence suggests impaired second order configural processing, more studies are necessary to determine whether or not holistic processing is impaired in schizophrenia patients. Neural and neurophysiological evidence suggests impaired earlier levels of visual processing, which might involve the deficits in interaction of the magnocellular and parvocellular pathways impacting on further processing. These deficits seem to be present even before the disorder out-set. Although evidence suggests that this deficit may be not specific to faces, further evidence on this question is necessary, in particularly more ecological studies including context and body processing.
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Affiliation(s)
- Catherine Bortolon
- Epsylon Laboratory, EA 4556 Montpellier, France; University Department of Adult Psychiatry, CHU Montpellier, Montpellier, France.
| | - Delphine Capdevielle
- University Department of Adult Psychiatry, CHU Montpellier, Montpellier, France; French National Institute of Health and Medical Research (INSERM), U1061 Pathologies of the Nervous System: Epidemiological and Clinical Research, La Colombiere Hospital, 34093 Montpellier Cedex 5, France
| | - Stéphane Raffard
- Epsylon Laboratory, EA 4556 Montpellier, France; University Department of Adult Psychiatry, CHU Montpellier, Montpellier, France
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Sarkheil P, Zilverstand A, Kilian-Hütten N, Schneider F, Goebel R, Mathiak K. fMRI feedback enhances emotion regulation as evidenced by a reduced amygdala response. Behav Brain Res 2015; 281:326-32. [DOI: 10.1016/j.bbr.2014.11.027] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 11/09/2014] [Accepted: 11/15/2014] [Indexed: 11/27/2022]
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Junghöfer M, Bröckelmann AK, Küppers K, Ohrmann P, Pedersen A. Abnormal, affect-specific modulatory effects on early auditory processing in schizophrenia: magnetoencephalographic evidence. Schizophr Res 2015; 161:308-13. [PMID: 25497223 DOI: 10.1016/j.schres.2014.11.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Revised: 11/17/2014] [Accepted: 11/19/2014] [Indexed: 11/26/2022]
Abstract
Abnormalities in the perception and identification of emotions have frequently been reported in schizophrenia. Hemodynamic neuroimaging studies found functional abnormalities in cortical and subcortical brain circuits that are involved in normal affective processing, but the temporal dynamics of abnormal emotion processing in schizophrenia remain largely elusive. To investigate this issue, we recorded early auditory evoked field components by means of whole-head magnetoencephalography that were in response to emotion-associated tones in seventeen patients with schizophrenia and in seventeen healthy, matched controls. Forty-two click-like tones (conditioned stimuli; CS) acquired differential emotional meaning through an affective associative learning procedure by pairing each CS three times with either pleasant, unpleasant or neutral auditory scenes. As expected, differential affect-specific modulation in patients vs. controls was evident, starting at the auditory N1m onset latency of approximately 70ms, extending to 230ms. While controls showed the expected enhanced processing of emotion associated CS, patients revealed an inverted pattern with reduced processing of arousal, when compared to neutral stimuli, in the right prefrontal cortex. The present finding suggests impairments in the prioritization of emotionally salient vs. non-salient stimuli in patients with schizophrenia. Dysfunction in higher cognitive processes and behavior in schizophrenia may therefore reflect dysfunction in fundamental, early emotion processing stages.
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Affiliation(s)
- Markus Junghöfer
- Institute for Biomagnetism and Biosignalanalysis, University Hospital Münster, D-48149 Münster, Germany
| | - Ann-Kathrin Bröckelmann
- Institute for Biomagnetism and Biosignalanalysis, University Hospital Münster, D-48149 Münster, Germany
| | - Kerstin Küppers
- Department of Psychology, Clinical Psychology and Psychotherapy, University Münster, D-48149 Münster, Germany
| | - Patricia Ohrmann
- Department of Psychiatry, School of Medicine, University of Münster, D-48149 Münster, Germany
| | - Anya Pedersen
- Department of Psychology, Clinical Psychology and Psychotherapy, University Münster, D-48149 Münster, Germany; Department of Psychology, Clinical Psychology and Psychotherapy, University Kiel, D-24118 Kiel, Germany.
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Li C, Rainnie DG. Bidirectional regulation of synaptic plasticity in the basolateral amygdala induced by the D1-like family of dopamine receptors and group II metabotropic glutamate receptors. J Physiol 2014; 592:4329-51. [PMID: 25107924 PMCID: PMC4215780 DOI: 10.1113/jphysiol.2014.277715] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Accepted: 07/22/2014] [Indexed: 12/31/2022] Open
Abstract
Competing mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in principal neurons of the basolateral amygdala (BLA) are thought to underlie the acquisition and consolidation of fear memories, and their subsequent extinction. However, no study to date has examined the locus of action and/or the cellular mechanism(s) by which these processes interact. Here, we report that synaptic plasticity in the cortical pathway onto BLA principal neurons is frequency-dependent and shows a transition from LTD to LTP at stimulation frequencies of ∼10 Hz. At the crossover point from LTD to LTP induction we show that concurrent activation of D1 and group II metabotropic glutamate (mGluR2/3) receptors act to nullify any net change in synaptic strength. Significantly, blockade of either D1 or mGluR2/3 receptors unmasked 10 Hz stimulation-induced LTD and LTP, respectively. Significantly, prior activation of presynaptic D1 receptors caused a time-dependent attenuation of mGluR2/3-induced depotentiation of previously induced LTP. Furthermore, studies with cell type-specific postsynaptic transgene expression of designer receptors activated by designer drugs (DREADDs) suggest that the interaction results via bidirectional modulation of adenylate cyclase activity in presynaptic glutamatergic terminals. The results of our study raise the possibility that the temporal sequence of activation of either presynaptic D1 receptors or mGluR2/3 receptors may critically regulate the direction of synaptic plasticity in afferent pathways onto BLA principal neurons. Hence, the interaction of these two neurotransmitter systems may represent an important mechanism for bidirectional metaplasticity in BLA circuits and thus modulate the acquisition and extinction of fear memory.
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Affiliation(s)
- Chenchen Li
- Division of Behavioural Neuroscience & Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, 30329, USA Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, 30329, USA
| | - Donald G Rainnie
- Division of Behavioural Neuroscience & Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, 30329, USA Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, 30329, USA
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26
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Attwood AS, Munafò MR. Effects of acute alcohol consumption and processing of emotion in faces: Implications for understanding alcohol-related aggression. J Psychopharmacol 2014; 28:719-32. [PMID: 24920135 PMCID: PMC4962899 DOI: 10.1177/0269881114536476] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The negative consequences of chronic alcohol abuse are well known, but heavy episodic consumption ("binge drinking") is also associated with significant personal and societal harms. Aggressive tendencies are increased after alcohol but the mechanisms underlying these changes are not fully understood. While effects on behavioural control are likely to be important, other effects may be involved given the widespread action of alcohol. Altered processing of social signals is associated with changes in social behaviours, including aggression, but until recently there has been little research investigating the effects of acute alcohol consumption on these outcomes. Recent work investigating the effects of acute alcohol on emotional face processing has suggested reduced sensitivity to submissive signals (sad faces) and increased perceptual bias towards provocative signals (angry faces) after alcohol consumption, which may play a role in alcohol-related aggression. Here we discuss a putative mechanism that may explain how alcohol consumption influences emotional processing and subsequent aggressive responding, via disruption of orbitofrontal cortex (OFC)-amygdala connectivity. While the importance of emotional processing on social behaviours is well established, research into acute alcohol consumption and emotional processing is still in its infancy. Further research is needed and we outline a research agenda to address gaps in the literature.
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Affiliation(s)
- Angela S Attwood
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK UK Centre for Tobacco and Alcohol Studies, Bristol, UK School of Experimental Psychology, University of Bristol, Bristol, UK
| | - Marcus R Munafò
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK UK Centre for Tobacco and Alcohol Studies, Bristol, UK School of Experimental Psychology, University of Bristol, Bristol, UK
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Champagne J, Mendrek A, Germain M, Hot P, Lavoie ME. Event-related brain potentials to emotional images and gonadal steroid hormone levels in patients with schizophrenia and paired controls. Front Psychol 2014; 5:543. [PMID: 24966840 PMCID: PMC4052747 DOI: 10.3389/fpsyg.2014.00543] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 05/16/2014] [Indexed: 12/05/2022] Open
Abstract
Prominent disturbances in the experience, expression, and emotion recognition in patients with schizophrenia have been relatively well documented over the last few years. Furthermore, sex differences in behavior and brain activity, associated with the processing of various emotions, have been reported in the general population and in schizophrenia patients. Others proposed that sex differences should be rather attributed to testosterone, which may play a role in the etiology of schizophrenia. Also, it had been suggested that estradiol may play a protective role in schizophrenia. Surprisingly, few studies investigating this pathology have focused on both brain substrates and gonadal steroid hormone levels, in emotional processing. In the present study, we investigated electrocortical responses related to emotional valence and arousal as well as gonadal steroid hormone levels in patients with schizophrenia. Event-Related Potentials (ERP) were recorded during exposition to emotional pictures in 18 patients with schizophrenia and in 24 control participants paired on intelligence, manual dominance and socioeconomic status. Given their previous sensitivity to emotional and attention processes, the P200, N200 and the P300 were selected for analysis. More precisely, emotional valence generally affects early components (N200), which reflect early process of selective attention, whereas emotional arousal and valence both influences the P300 component, which is related to memory context updating, and stimulus categorization. Results showed that, in the control group, the amplitude of the N200 was significantly more lateralized over the right hemisphere, while there was no such lateralization in patients with schizophrenia. In patients with schizophrenia, significantly smaller anterior P300 amplitude was observed to the unpleasant, compared to the pleasant. That anterior P300 reduction was also correlated with negative symptoms. The N200 and P300 amplitudes were positively correlated with the estradiol level in all conditions, revealing that the N200 and the P300 were reduced, when estradiol level was higher. Conversely, only the P300 amplitude showed positive correlation with the testosterone level.
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Affiliation(s)
- Julie Champagne
- Axe de Neurobiologie Cognitive, Laboratoire de Psychophysiologie Cognitive et Sociale, Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal Montréal, QC, Canada ; Department of Psychiatry, Université de Montréal Montréal, QC, Canada
| | - Adrianna Mendrek
- Axe de Neurobiologie Cognitive, Laboratoire de Psychophysiologie Cognitive et Sociale, Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal Montréal, QC, Canada ; Department of Psychology, Bishop's University, Sherbrooke QC, Canada
| | - Martine Germain
- Axe de Neurobiologie Cognitive, Laboratoire de Psychophysiologie Cognitive et Sociale, Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal Montréal, QC, Canada ; Department of Psychiatry, Université de Montréal Montréal, QC, Canada
| | - Pascal Hot
- Laboratoire de Psychologie et Neurocognition, Université de Savoie Chambéry, France
| | - Marc E Lavoie
- Axe de Neurobiologie Cognitive, Laboratoire de Psychophysiologie Cognitive et Sociale, Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal Montréal, QC, Canada ; Department of Psychiatry, Université de Montréal Montréal, QC, Canada
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Bergé D, Carmona S, Salgado P, Rovira M, Bulbena A, Vilarroya O. Limbic activity in antipsychotic naïve first-episode psychotic subjects during facial emotion discrimination. Eur Arch Psychiatry Clin Neurosci 2014; 264:271-83. [PMID: 24258969 DOI: 10.1007/s00406-013-0465-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Accepted: 10/16/2013] [Indexed: 11/29/2022]
Abstract
The aim of this study was to determine brain activation during facial emotion discrimination in first-episode of psychosis. Eighteen patients underwent an fMRI while performing a facial emotion discrimination task during the acute episode, before starting antipsychotic drugs. A second fMRI and clinical evaluation were performed after evident clinical improvement. An equivalent control group underwent the same two fMRIs with a similar period of time between exams. The voxel-wise approach showed pre-treatment hypoactivation in ventro-limbic regions (cluster including right hippocampus and left amygdala; cluster size 528; p cluster <0.004) and facial perception involved in ventral-posterior regions (bilateral lingual gyrus, calcarine fissure and occipital superior gyrus, (k = 1,508, p < 0.001) and fronto-temporal regions. The region of interest approach also confirmed hypoactivation in right and left amygdala (cluster corrected p = 0.035 and 0.043, respectively). After treatment and clinical improvement, the voxel-wise approach showed a significant increase in activity in lingual gyrus and calcarine fissure in the group of patients. The regions of interest analysis showed an increase in amygdala activity during anger discrimination also in the group of patients. The results suggest a state-dependent model depicting a flattened and aberrant response of amygdala to emotion discrimination that could explain the seemingly contradictory previous findings of hypo- and hyper-amygdala activation.
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Affiliation(s)
- Daniel Bergé
- Institute of Neuropsychiatry and Addictions, Parc de Salut Mar, Centre Forum Hospital del Mar, Barcelona, Spain,
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Dyck M, Loughead J, Gur RC, Schneider F, Mathiak K. Hyperactivation balances sensory processing deficits during mood induction in schizophrenia. Soc Cogn Affect Neurosci 2014; 9:167-75. [PMID: 23051903 PMCID: PMC3907924 DOI: 10.1093/scan/nss120] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2012] [Accepted: 10/04/2012] [Indexed: 11/14/2022] Open
Abstract
While impairments in emotion recognition are consistently reported in schizophrenia, there is some debate on the experience of emotion. Only few studies investigated neural correlates of emotional experience in schizophrenia. The present functional magnetic resonance imaging study compared a standard visual mood induction paradigm with an audiovisual method aimed at eliciting emotions more automatically. To investigate the interplay of sensory, cognitive and emotional mechanisms during emotion experience, we examined connectivity patterns between brain areas. Sixteen schizophrenia patients and sixteen healthy subjects participated in two different mood inductions (visual and audiovisual) that were administered for different emotions (happiness, sadness and neutral). Confirming the dissociation of behavioral and neural correlates of emotion experience, patients rated their mood similarly to healthy subjects but showed differences in neural activations. Sensory brain areas were activated less, increased activity emerged in higher cortical areas, particularly during audiovisual stimulation. Connectivity was increased between primary and secondary sensory processing areas in schizophrenia. These findings support the hypothesis of a deficit in filtering and processing sensory information alongside increased higher-order cognitive effort compensating for perception deficits in the affective domain. This may suffice to recover emotion experience in ratings of clinically stable patients but may fail during acute psychosis.
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Affiliation(s)
- Miriam Dyck
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
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Lindner C, Dannlowski U, Walhöfer K, Rödiger M, Maisch B, Bauer J, Ohrmann P, Lencer R, Zwitserlood P, Kersting A, Heindel W, Arolt V, Kugel H, Suslow T. Social alienation in schizophrenia patients: association with insula responsiveness to facial expressions of disgust. PLoS One 2014; 9:e85014. [PMID: 24465469 PMCID: PMC3898910 DOI: 10.1371/journal.pone.0085014] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2013] [Accepted: 11/26/2013] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Among the functional neuroimaging studies on emotional face processing in schizophrenia, few have used paradigms with facial expressions of disgust. In this study, we investigated whether schizophrenia patients show less insula activation to macro-expressions (overt, clearly visible expressions) and micro-expressions (covert, very brief expressions) of disgust than healthy controls. Furthermore, departing from the assumption that disgust faces signal social rejection, we examined whether perceptual sensitivity to disgust is related to social alienation in patients and controls. We hypothesized that high insula responsiveness to facial disgust predicts social alienation. METHODS We used functional magnetic resonance imaging to measure insula activation in 36 schizophrenia patients and 40 healthy controls. During scanning, subjects passively viewed covert and overt presentations of disgust and neutral faces. To measure social alienation, a social loneliness scale and an agreeableness scale were administered. RESULTS Schizophrenia patients exhibited reduced insula activation in response to covert facial expressions of disgust. With respect to macro-expressions of disgust, no between-group differences emerged. In patients, insula responsiveness to covert faces of disgust was positively correlated with social loneliness. Furthermore, patients' insula responsiveness to covert and overt faces of disgust was negatively correlated with agreeableness. In controls, insula responsiveness to covert expressions of disgust correlated negatively with agreeableness. DISCUSSION Schizophrenia patients show reduced insula responsiveness to micro-expressions but not macro-expressions of disgust compared to healthy controls. In patients, low agreeableness was associated with stronger insula response to micro- and macro-expressions of disgust. Patients with a strong tendency to feel uncomfortable with social interactions appear to be characterized by a high sensitivity for facial expression signaling social rejection. Given the associations of insula responsiveness to covert disgust expression with low agreeableness in healthy individuals, insula responsiveness to expressions of disgust might be in general a neural marker of the personality trait of agreeableness.
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Affiliation(s)
| | - Udo Dannlowski
- Department of Psychiatry, University of Münster, Münster, Germany
- Department of Psychiatry, University of Marburg, Marburg, Germany
| | - Kirsten Walhöfer
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Maike Rödiger
- Department of Psychiatry, University of Münster, Münster, Germany
| | | | - Jochen Bauer
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Patricia Ohrmann
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Rebekka Lencer
- Department of Psychiatry, University of Münster, Münster, Germany
| | | | - Anette Kersting
- Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, Germany
| | - Walter Heindel
- Department of Clinical Radiology, University of Münster, Münster, Germany
| | - Volker Arolt
- Department of Psychiatry, University of Münster, Münster, Germany
| | - Harald Kugel
- Department of Clinical Radiology, University of Münster, Münster, Germany
| | - Thomas Suslow
- Department of Psychiatry, University of Münster, Münster, Germany
- Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, Germany
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Horga G, Fernández-Egea E, Mané A, Font M, Schatz KC, Falcon C, Lomeña F, Bernardo M, Parellada E. Brain metabolism during hallucination-like auditory stimulation in schizophrenia. PLoS One 2014; 9:e84987. [PMID: 24416328 PMCID: PMC3885666 DOI: 10.1371/journal.pone.0084987] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 11/25/2013] [Indexed: 11/19/2022] Open
Abstract
Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia.
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Affiliation(s)
- Guillermo Horga
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York, United States of America
- Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, Barcelona, Spain
- Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
- * E-mail:
| | - Emilio Fernández-Egea
- Department of Psychiatry, University of Cambridge, Cambridge, and the Cambridgeshire and Peterborough NHS Foundation Trust, Huntingdon, United Kingdom
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Anna Mané
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Centre Forum, Barcelona, Spain
| | - Mireia Font
- Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, Barcelona, Spain
| | - Kelly C. Schatz
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York, United States of America
| | | | - Francisco Lomeña
- Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Miguel Bernardo
- Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, Barcelona, Spain
- Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Eduard Parellada
- Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, Barcelona, Spain
- Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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Individuals diagnosed with schizophrenia assign emotional importance to neutral stimuli: an FMRI study. ISRN PSYCHIATRY 2013; 2013:965428. [PMID: 24381781 PMCID: PMC3871502 DOI: 10.1155/2013/965428] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Accepted: 11/13/2013] [Indexed: 11/17/2022]
Abstract
The majority of functional neuroimaging studies investigating neural correlates of emotion processing in schizophrenia report a significant deficit in limbic structures activation in patients relative to control participants. Recently it has been suggested that this apparent "deficit" could be due to an enhanced sensitivity of the neutral material in individuals diagnosed with schizophrenia, rather than due to their inefficiency in emotion processing. The purpose of the present study was to test this supposition and verify if the potential effect is present in both men and women diagnosed with schizophrenia. In order to do that we examined the pattern of cerebral activation associated with processing of neutral stimuli in schizophrenia. Thirty-seven schizophrenia patients and 37 healthy controls viewed neutral and emotional images while in a functional magnetic resonance imaging scanner. Schizophrenia patients rated the neutral images as more emotionally salient than controls. Additionally, patients showed significant activation during processing of neutral images in limbic and prefrontal regions; similar areas were underactivated in patients relative to controls during processing of emotional information. Investigation of sex differences revealed that the enhanced responsiveness to the emotionally neutral material was attributed primarily to men with schizophrenia.
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Suslow T, Lindner C, Dannlowski U, Walhöfer K, Rödiger M, Maisch B, Bauer J, Ohrmann P, Lencer R, Zwitserlood P, Kersting A, Heindel W, Arolt V, Kugel H. Automatic amygdala response to facial expression in schizophrenia: initial hyperresponsivity followed by hyporesponsivity. BMC Neurosci 2013; 14:140. [PMID: 24219776 PMCID: PMC3832234 DOI: 10.1186/1471-2202-14-140] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Accepted: 11/08/2013] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND It is well established that the amygdala is crucially involved in the processing of facial emotions. In schizophrenia patients, a number of neuroimaging findings suggest hypoactivation of the amygdala in response to facial emotion, while others indicate normal or enhanced recruitment of this region. Some of this variability may be related to the baseline condition used and the length of the experiment. There is evidence that schizophrenia patients display increased activation of the amygdala to neutral faces and that this is predominantly observed during early parts of the experiment. Recent research examining the automatic processing of facial emotion has also reported amygdala hyperactivation in schizophrenia. In the present study, we focused on the time-course of amygdala activation during the automatic processing of emotional facial expression. We hypothesized that in comparison to healthy subjects, patients would initially show hyperresponsivity of the amygdala to masked emotional and neutral faces. In addition, we expected amygdala deactivation in response to masked facial emotions from the first to the second phase to be more pronounced in patients than in controls. RESULTS Amygdala activation in response to angry, happy, neutral, and no facial expression (presented for 33 ms) was measured by functional magnetic resonance imaging in 30 schizophrenia patients and 35 healthy controls. Across all subjects, the bilateral amygdala response to faces (relative to the no facial expression condition) was larger in the initial phase (first half of trials) than in the second phase (second half of trials). During the initial phase, schizophrenia patients exhibited an increased right amygdala response to all faces and an increased left amygdala response to neutral faces compared with controls. During the second phase, controls manifested a higher right amygdala response for all faces and a higher left amygdala response to angry faces than patients. CONCLUSIONS Schizophrenia patients are characterized by high initial amygdala responsivity to facial expressions at an automatic processing level, which substantially decreases with time. Amygdala deactivation over time might reflect an automatic mechanism by which schizophrenia patients suppress the processing of facial stimuli. This blocking mechanism could help patients avoid overstimulation during social interactions.
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Affiliation(s)
- Thomas Suslow
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
- Department of Psychosomatic Medicine, University of Leipzig, Semmelweisstr 10, Leipzig 04103, Germany
| | - Christian Lindner
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Udo Dannlowski
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
- Department of Psychiatry, University of Marburg, Rudolf-Bultmann-Str. 8, Marburg 35037, Germany
| | - Kirsten Walhöfer
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Maike Rödiger
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Birgit Maisch
- Klinik am Schlossgarten, Am Schlossgarten 10, Dülmen 48249, Germany
| | - Jochen Bauer
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Patricia Ohrmann
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Rebekka Lencer
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Pienie Zwitserlood
- Department of Psychology, University of Münster, Fliednerstr. 21, Münster 48149, Germany
| | - Anette Kersting
- Department of Psychosomatic Medicine, University of Leipzig, Semmelweisstr 10, Leipzig 04103, Germany
| | - Walter Heindel
- Department of Clinical Radiology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, Germany
| | - Volker Arolt
- Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, Münster 48149, Germany
| | - Harald Kugel
- Department of Clinical Radiology, University of Münster, Albert-Schweitzer-Campus 1, Münster 48149, Germany
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Abstract
In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts - indexed by area-level exposures such as population density, social fragmentation and deprivation - on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date.
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Affiliation(s)
- Andreas Heinz
- Department of Psychiatry, Charité-Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany
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Pankow A, Friedel E, Sterzer P, Seiferth N, Walter H, Heinz A, Schlagenhauf F. Altered amygdala activation in schizophrenia patients during emotion processing. Schizophr Res 2013; 150:101-6. [PMID: 23911256 DOI: 10.1016/j.schres.2013.07.015] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Revised: 06/15/2013] [Accepted: 07/05/2013] [Indexed: 10/26/2022]
Abstract
Dysfunctional emotion processing in patients suffering from schizophrenia is a prominent clinical feature of great importance for social functioning and subjective well-being. The neurobiological underpinnings are still poorly understood. Here we investigated a large sample of schizophrenia patients and matched healthy controls with an event-related fMRI task during emotion processing using emotional pictures from the International Affective Picture System (IAPS). Schizophrenia patients revealed stronger right amygdala activation during negative and attenuated response during positive affective picture processing compared to healthy controls. Further analysis indicated that medication status influences activation of the ventral anterior cingulate cortex during negative affective stimuli processing. These results might represent a correlate of altered emotional experience in schizophrenia patients who are known to report less positive and more negative affective states in daily life situations.
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Affiliation(s)
- Anne Pankow
- Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Charité Campus Mitte, Germany.
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36
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Darke H, Peterman JS, Park S, Sundram S, Carter O. Are patients with schizophrenia impaired in processing non-emotional features of human faces? Front Psychol 2013; 4:529. [PMID: 23970872 PMCID: PMC3747312 DOI: 10.3389/fpsyg.2013.00529] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 07/26/2013] [Indexed: 11/13/2022] Open
Abstract
It is known that individuals with schizophrenia exhibit signs of impaired face processing, however, the exact perceptual and cognitive mechanisms underlying these deficits are yet to be elucidated. One possible source of confusion in the current literature is the methodological and conceptual inconsistencies that can arise from the varied treatment of different aspects of face processing relating to emotional and non-emotional aspects of face perception. This review aims to disentangle the literature by focusing on the performance of patients with schizophrenia in a range of tasks that required processing of non-emotional features of face stimuli (e.g., identity or gender). We also consider the performance of patients on non-face stimuli that share common elements such as familiarity (e.g., cars) and social relevance (e.g., gait). We conclude by exploring whether observed deficits are best considered as “face-specific” and note that further investigation is required to properly assess the potential contribution of more generalized attentional or perceptual impairments.
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Affiliation(s)
- Hayley Darke
- School of Psychological Sciences, University of Melbourne Parkville, VIC, Australia
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37
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Martin EA, Becker TM, Cicero DC, Kerns JG. Examination of affective and cognitive interference in schizophrenia and relation to symptoms. JOURNAL OF ABNORMAL PSYCHOLOGY 2013; 122:733-744. [PMID: 24016013 PMCID: PMC6095466 DOI: 10.1037/a0033956] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The nature of emotion deficits in schizophrenia and anhedonia is still unclear, and understanding the nature of these deficits could help improve treatment of chronic symptoms and functional disability. An important mechanism in emotional functioning is attention to affective information. People with schizophrenia (n = 48) and a nonpsychiatric comparison group (n = 28) completed an affective interference task, a task used to assess attention to affective information. Given that the affective interference task also involves prepotent response inhibition, participants also completed a very similar, but nonaffective, cognitive interference task that involves prepotent inhibition but does not require attention to affective information. Results revealed that people with schizophrenia exhibited decreased affective interference on trials with a shorter length of time between the onset of the cue and onset of the target but increased cognitive interference at all time lengths between the cue and target onsets used in the study. In addition, decreased affective interference was associated with increased anhedonia and increased reports of wanting to ignore positive emotions. In contrast, increased cognitive interference was associated with increased communication disturbances and alogia. Overall, these results suggest that there may be a decrease in attention to affective information in schizophrenia and that affective interference is related to anhedonia. At the same time, these results provide further evidence of cognitive control prepotent inhibition deficits in schizophrenia, which are related to communication disturbances and alogia.
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38
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Nahum M, Lee H, Merzenich MM. Principles of Neuroplasticity-Based Rehabilitation. PROGRESS IN BRAIN RESEARCH 2013; 207:141-71. [DOI: 10.1016/b978-0-444-63327-9.00009-6] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2023]
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Whalley HC, Papmeyer M, Romaniuk L, Sprooten E, Johnstone EC, Hall J, Lawrie SM, Evans KL, Blumberg HP, Sussmann JE, McIntosh AM. Impact of a microRNA MIR137 susceptibility variant on brain function in people at high genetic risk of schizophrenia or bipolar disorder. Neuropsychopharmacology 2012; 37:2720-9. [PMID: 22850735 PMCID: PMC3473338 DOI: 10.1038/npp.2012.137] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2012] [Revised: 05/25/2012] [Accepted: 06/18/2012] [Indexed: 02/08/2023]
Abstract
A recent 'mega-analysis' combining genome-wide association study data from over 40,000 individuals identified novel genetic loci associated with schizophrenia (SCZ) at genome-wide significance level. The strongest finding was a locus within an intron of a putative primary transcript for microRNA MIR137. In the current study, we examine the impact of variation at this locus (rs1625579, G/T; where T is the common and presumed risk allele) on brain activation during a sentence completion task that differentiates individuals with SCZ, bipolar disorder (BD), and their relatives from controls. We examined three groups of individuals performing a sentence completion paradigm: (i) individuals at high genetic risk of SCZ (n=44), (ii) individuals at high genetic risk of BD (n=90), and (iii) healthy controls (n=81) in order to test the hypothesis that genotype at rs1625579 would influence brain activation. Genotype groups were assigned as 'RISK-' for GT and GG individuals, and 'RISK+' for TT homozygotes. The main effect of genotype was significantly greater activation in the RISK- individuals in the posterior right medial frontal gyrus, BA 6. There was also a significant genotype(*)group interaction in the left amygdala and left pre/postcentral gyrus. This was due to differences between the controls (where individuals with the RISK- genotype showed greater activation than RISK+ subjects) and the SCZ high-risk group, where the opposite genotype effect was seen. These results suggest that the newly identified SCZ locus may influence brain activation in a manner that is partly dependent on the presence of existing genetic susceptibility for SCZ.
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Affiliation(s)
- Heather C Whalley
- Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
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40
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Anticevic A, Repovs G, Barch DM. Emotion effects on attention, amygdala activation, and functional connectivity in schizophrenia. Schizophr Bull 2012; 38:967-80. [PMID: 21415225 PMCID: PMC3446234 DOI: 10.1093/schbul/sbq168] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/13/2010] [Indexed: 11/14/2022]
Abstract
Emotional abnormalities are a critical clinical feature of schizophrenia (SCZ), but complete understanding of their underlying neuropathology is lacking. Numerous studies have examined amygdala activation in response to affective stimuli in SCZ, but no consensus has emerged. However, behavioral studies examining 'in-the-moment' processing of affect have suggested intact emotional processing in SCZ. To examine which aspects of emotional processing may be impaired in SCZ, we combined behavior and neuroimaging to investigate effects of aversive stimuli during minimal cognitive engagement, at the level of behavior, amygdala recruitment, and its whole-brain task-based functional connectivity (tb-fcMRI) because impairments may manifest when examining across-region functional integration. Twenty-eight patients and 24 matched controls underwent rapid event-related fMRI at 3 T while performing a simple perceptual decision task with negative or neutral distraction. We examined perceptual decision slowing, amygdala activation, and whole-brain amygdala tb-fcMRI, while ensuring group signal-to-noise profile matching. Following scanning, subjects rated all images for experienced arousal and valence. No significant group differences emerged for negative vs neutral reaction time, emotional ratings across groups, or amygdala activation. However, even in the absence of behavioral or activation differences, SCZ subjects demonstrated significantly weaker amygdala-prefrontal cortical coupling, specifically during negative distraction. Whereas in-the-moment perception, behavioral response, and amygdala recruitment to negative stimuli during minimal cognitive load seem to be intact, there is evidence of aberrant amygdala-prefrontal integration in SCZ subjects. Such abnormalities may prove critical for understanding disturbances in patients' ability to use affective cues when guiding higher level cognitive processes needed in social interactions.
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Affiliation(s)
- Alan Anticevic
- Department of Psychology, Washington University, St. Louis, MO, USA.
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41
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Lee JS, Chun JW, Kang JI, Kang DI, Park HJ, Kim JJ. Hippocampus and nucleus accumbens activity during neutral word recognition related to trait physical anhedonia in patients with schizophrenia: an fMRI study. Psychiatry Res 2012; 203:46-53. [PMID: 22867952 DOI: 10.1016/j.pscychresns.2011.09.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2011] [Revised: 08/24/2011] [Accepted: 09/07/2011] [Indexed: 01/19/2023]
Abstract
Emotional memory dysfunction may be associated with anhedonia in schizophrenia. This study aimed to investigate the neurobiological basis of emotional memory and its relationship with anhedonia in schizophrenia specifically in emotional memory relate brain regions of interest (ROIs) including the amygdala, hippocampus, nucleus accumbens, and ventromedial prefrontal cortex. Fourteen patients with schizophrenia and 16 healthy subjects performed a word-image associative encoding task, during which a neutral word was presented with a positive, neutral, or control image. Subjects underwent functional magnetic resonance imaging while performing the recognition task. Correlation analyses were performed between the percent signal change (PSC) in the ROIs and the anhedonia scores. We found no group differences in recognition accuracy and reaction time. The PSC of the hippocampus in the positive and neutral conditions, and the PSC in the nucleus accumbens in the control condition, appeared to be negatively correlated with the Physical Anhedonia Scale (PAS) scores in patients with schizophrenia, while significant correlations with the PAS scores were not observed in healthy subjects. This study provides further evidences of the role of the hippocampus and nucleus accumbens in trait physical anhedonia and possible associations between emotional memory deficit and trait physical anhedonia in patients with schizophrenia.
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Affiliation(s)
- Jung Suk Lee
- Department of Psychiatry, Bundang Jesaeng Hospital, Seohyeon-dong, Bundang-gu, Seongnam, Gyeonggi-do, South Korea
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Whalley HC, Papmeyer M, Sprooten E, Lawrie SM, Sussmann JE, McIntosh AM. Review of functional magnetic resonance imaging studies comparing bipolar disorder and schizophrenia. Bipolar Disord 2012; 14:411-31. [PMID: 22631622 DOI: 10.1111/j.1399-5618.2012.01016.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Although bipolar disorder (BD) and schizophrenia (SCZ) have a number of clinical features and certain susceptibility genes in common, they are considered separate disorders, and it is unclear which aspects of pathophysiology are specific to each condition. Here, we examine the functional magnetic resonance imaging (fMRI) literature to determine the evidence for diagnosis-specific patterns of brain activation in the two patient groups. METHOD A systematic search was performed to identify fMRI studies directly comparing BD and SCZ to examine evidence for diagnosis-specific activation patterns. Studies were categorized into (i) those investigating emotion, reward, or memory, (ii) those describing executive function or language tasks, and (iii) those looking at the resting state or default mode networks. Studies reporting estimates of sensitivity and specificity of classification are also summarized, followed by studies reporting associations with symptom severity measures. RESULTS In total, 21 studies were identified including patients (n = 729) and healthy subjects (n = 465). Relative over-activation in the medial temporal lobe and associated structures was found in BD versus SCZ in tasks involving emotion or memory. Evidence of differences between the disorders in prefrontal regions was less consistent. Accuracy values for assignment of diagnosis were generally lower in BD than in SCZ. Few studies reported significant symptom associations; however, these generally implicated limbic regions in association with manic symptoms. CONCLUSIONS Although there are a limited number of studies and a cautious approach is warranted, activation differences were found in the medial temporal lobe and associated limbic regions, suggesting the presence of differences in the neurobiological substrates of SCZ and BD. Future studies examining symptom dimensions, risk-associated genes, and the effects of medication will aid clarification of the mechanisms behind these differences.
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Affiliation(s)
- Heather C Whalley
- Division of Psychiatry, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK.
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Deficits in emotional learning and memory in an animal model of schizophrenia. Behav Brain Res 2012; 233:35-44. [PMID: 22569573 DOI: 10.1016/j.bbr.2012.04.049] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Revised: 04/05/2012] [Accepted: 04/28/2012] [Indexed: 11/23/2022]
Abstract
Alterations in N-methyl-D-aspartate (NMDA) receptor function have been linked to numerous behavioral deficits and neurochemical alterations. Recent investigations have begun to explore the role of NMDA receptor function on principally inhibitory neurons and their role in network function. One of the prevailing models of schizophrenia proposes a reduction in NMDA receptor function on inhibitory interneurons and the resulting disinhibition may give rise to aspects of the disorder. Studies using NMDA receptor antagonists such as PCP and ketamine have induced schizophrenia-like behavioral deficits in animal model systems as well as changes in inhibitory circuits. The current study investigated whether the administration of a subanesthetic dose of ketamine (8 mg/kg subcutaneously), that disrupts sensorimotor gating, also produces impairments in a Pavlovian emotional learning and memory task. We utilized both standard delay and trace cued and contextual fear conditioning (CCF) paradigms to examine if ketamine produces differential effects when the task is more difficult and relies on connectivity between specific brain regions. Rats administered ketamine displayed no significant deficits in cued or contextual fear following the delay conditioning protocol. However, ketamine did produce a significant impairment in the more difficult trace conditioning protocol. Analyses of tissue from the hippocampus and amygdala indicated that the administration of ketamine produced an alteration in GABA receptor protein levels differentially depending on the task. These data indicate that 8 mg/kg of ketamine impairs learning in the more difficult emotional classical conditioning task and may be related to altered signaling in GABAergic systems.
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Anticevic A, Van Snellenberg JX, Cohen RE, Repovs G, Dowd EC, Barch DM. Amygdala recruitment in schizophrenia in response to aversive emotional material: a meta-analysis of neuroimaging studies. Schizophr Bull 2012; 38:608-21. [PMID: 21123853 PMCID: PMC3329999 DOI: 10.1093/schbul/sbq131] [Citation(s) in RCA: 141] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Emotional dysfunction has long been established as a critical clinical feature of schizophrenia. In the past decade, there has been extensive work examining the potential contribution of abnormal amygdala activation to this dysfunction in patients with schizophrenia. A number of studies have demonstrated under-recruitment of the amygdala in response to emotional stimuli, while others have shown intact recruitment of this region. To date, there have been few attempts to synthesize this literature using quantitative criteria or to use a formal meta-analytic approach to examine which variables may moderate the magnitude of between-group differences in amygdala activation in response to aversive emotional stimuli. We conducted a meta-analysis of amygdala activation in patients with schizophrenia, using a bootstrapping approach to investigate: (a) evidence for amygdala under-recruitment in schizophrenia and (b) variables that may moderate the magnitude of between-group differences in amygdala activation. We demonstrate that patients with schizophrenia show statistically significant, but modest, under-recruitment of bilateral amygdala (mean effect size = -0.20 SD). However, present findings indicate that this under-recruitment is dependent on the use of a neutral vs emotion interaction contrast and is not apparent if amygdala activation by patients and controls is evaluated in a negative emotional condition only.
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Affiliation(s)
- Alan Anticevic
- Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA.
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Anticevic A, Van Snellenberg JX, Barch DM. Neurobiology of emotional dysfunction in schizophrenia: new directions revealed through meta-analyses. Biol Psychiatry 2012; 71:e23-4; author reply e25. [PMID: 22206874 DOI: 10.1016/j.biopsych.2011.10.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2011] [Accepted: 10/27/2011] [Indexed: 11/24/2022]
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Mendrek A, Bourque J, Dubé A, Lakis N, Champagne J. Emotion processing in women with schizophrenia is menstrual cycle phase and affective valence dependent: an FMRI study. ISRN PSYCHIATRY 2012; 2012:656274. [PMID: 23738207 PMCID: PMC3658698 DOI: 10.5402/2012/656274] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2011] [Accepted: 12/04/2011] [Indexed: 12/22/2022]
Abstract
Despite a large number of functional neuroimaging investigations of emotion processing in schizophrenia, very few have included women. In the present study 21 schizophrenia and 23 healthy women underwent functional MRI (3T) on two occasions (during the follicular and luteal phase of their menstrual cycle) while viewing blocks of emotionally negative, positive and neutral images. During exposure to negatively charged images patients showed relatively less activations than controls during the luteal phase, but no between-group differences were observed during the follicular phase. In contrast, the exposure to positively valenced material produced no significant interaction, but the main effect of group; schizophrenia patients exhibited less activation than healthy controls during both phases of the menstrual cycle. This is the first study demonstrating that atypical neural activations associated with emotion processing in women diagnosed with schizophrenia depend on the menstrual cycle phase and on the affective valence of presented stimuli.
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Affiliation(s)
- Adrianna Mendrek
- Centre de Recherche Fernand-Seguin, Department of Psychiatry, Université de Montréal, 7331 Hochelaga, Montreal, QC, Canada H1N 3V2
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Schock L, Dyck M, Demenescu LR, Edgar JC, Hertrich I, Sturm W, Mathiak K. Mood modulates auditory laterality of hemodynamic mismatch responses during dichotic listening. PLoS One 2012; 7:e31936. [PMID: 22384105 PMCID: PMC3285192 DOI: 10.1371/journal.pone.0031936] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Accepted: 01/16/2012] [Indexed: 11/24/2022] Open
Abstract
Hemodynamic mismatch responses can be elicited by deviant stimuli in a sequence of standard stimuli even during cognitive demanding tasks. Emotional context is known to modulate lateralized processing. Right-hemispheric negative emotion processing may bias attention to the right and enhance processing of right-ear stimuli. The present study examined the influence of induced mood on lateralized pre-attentive auditory processing of dichotic stimuli using functional magnetic resonance imaging (fMRI). Faces expressing emotions (sad/happy/neutral) were presented in a blocked design while a dichotic oddball sequence with consonant-vowel (CV) syllables in an event-related design was simultaneously administered. Twenty healthy participants were instructed to feel the emotion perceived on the images and to ignore the syllables. Deviant sounds reliably activated bilateral auditory cortices and confirmed attention effects by modulation of visual activity. Sad mood induction activated visual, limbic and right prefrontal areas. A lateralization effect of emotion-attention interaction was reflected in a stronger response to right-ear deviants in the right auditory cortex during sad mood. This imbalance of resources may be a neurophysiological correlate of laterality in sad mood and depression. Conceivably, the compensatory right-hemispheric enhancement of resources elicits increased ipsilateral processing.
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Affiliation(s)
- Lisa Schock
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.
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Li HJ, Chan RCK, Gong QY, Liu Y, Liu SM, Shum D, Ma ZL. Facial emotion processing in patients with schizophrenia and their non-psychotic siblings: a functional magnetic resonance imaging study. Schizophr Res 2012; 134:143-50. [PMID: 22113155 DOI: 10.1016/j.schres.2011.10.019] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2011] [Revised: 10/12/2011] [Accepted: 10/29/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND Previous studies have shown that patients with schizophrenia show abnormalities in brain activation when processing emotional faces. However, very few studies have examined if such abnormalities are also found in non-western patient samples and in at-risk individuals. The current study explored whether patients with schizophrenia and siblings of patients in China would show abnormal brain activation during processing of emotional faces. METHODS Thirty-six participants (three groups of twelve each of patients with schizophrenia, nonpsychotic siblings, and healthy controls) took part in the study. They were administered a task to judge emotional valence of three types of faces (viz., happy, fearful, and neutral), during fMRI scanning. RESULTS Results of this study demonstrated that patients with schizophrenia showed abnormalities in the social brain neural circuit during facial emotion processing, in comparison with nonpsychotic siblings and healthy controls. Patients with schizophrenia demonstrated lower activation right superior and middle frontal gyrus, left precentral gyrus, left middle temporal gyrus and left insula in comparison with healthy controls; and showed abnormal activation in bilateral inferior and middle frontal gyri, right orbital frontal gyrus, left superior and middle temporal gyrus, bilateral insula, and right superior parietal gyrus/postcentral gyrus when compared with their nonpyschotic siblings. Meanwhile, patients with schizophrenia showed greater activation in left middle frontal gyrus than healthy controls, and overactivation in bilateral middle frontal gyri, right orbital frontal gyrus and left middle temporal gyrus than their nonpsychotic siblings during processing of fearful faces. Moreover, nonpsychotic siblings seemed to share some similar dysfunctions in processing facial expressions as their psychotic probands, the two groups both showed abnormal activation in precentral and superior frontal gyri, and such abnormal activation lied between patients with schizophrenia and healthy controls. CONCLUSIONS The current findings support the universality of emotion perception impairments in schizophrenia, and also suggest that facial emotion perception might be a potential endophenotype of schizophrenia.
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Affiliation(s)
- Hui-Jie Li
- Neuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
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From semantics to feelings: how do individuals with schizophrenia rate the emotional valence of words? SCHIZOPHRENIA RESEARCH AND TREATMENT 2012; 2012:431823. [PMID: 22966437 PMCID: PMC3420789 DOI: 10.1155/2012/431823] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2011] [Accepted: 03/15/2012] [Indexed: 11/17/2022]
Abstract
Schizophrenia is characterized by both emotional and language abnormalities. However, in spite of reports of preserved evaluation of valence of affective stimuli, such as pictures, it is less clear how individuals with schizophrenia assess verbal material with emotional valence, for example, the overall unpleasantness/displeasure relative to pleasantness/attraction of a word. This study aimed to investigate how schizophrenic individuals rate the emotional valence of adjectives, when compared with a group of healthy controls. One hundred and eighty-four adjectives differing in valence were presented. These adjectives were previously categorized as "neutral," "positive" (pleasant), or "negative" (unpleasant) by five judges not participating in the current experiment. Adjectives from the three categories were matched on word length, frequency, and familiarity. Sixteen individuals with schizophrenia diagnosis and seventeen healthy controls were asked to rate the valence of each word, by using a computerized version of the Self-Assessment Manikin (Bradley and Lang, 1994). Results demonstrated similar ratings of emotional valence of words, suggesting a similar representation of affective knowledge in schizophrenia, at least in terms of the valence dimension.
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