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Li L, Wang L, Wu H, Li B, Pan W, Jin W, Wang W, Ren Y, Liu C, Ma X. Effects of parietal iTBS on resting-state effective connectivity within the frontoparietal network in patients with schizophrenia: An fMRI study. Neuroimage Clin 2024; 45:103715. [PMID: 39608227 PMCID: PMC11638604 DOI: 10.1016/j.nicl.2024.103715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 11/22/2024] [Accepted: 11/22/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND Although intermittent theta burst stimulation (iTBS) has shown effectiveness in addressing working memory (WM) deficits in individuals with schizophrenia (SZ), the current body of evidence is limited and the specific mechanisms involved remain unclear. Therefore, this pilot fMRI study aimed to examine the efficacy of parietal iTBS in ameliorating WM impairments and explore its influence on the resting-state effective connectivity within the frontoparietal network in patients with SZ. METHOD A total of 48 patients diagnosed with SZ were randomly assigned to an active or sham iTBS group and underwent 20 sessions of active or sham iTBS over 4 weeks. Subsequently, all patients underwent cognitive tests, clinical symptom assessments, and resting-state functional MRI (rs-fMRI) scans. The effective connectivity between the frontal and parietal brain regions during the rs-fMRI scans was analyzed using a spectral dynamic causal modeling approach. Additionally, this trial was registered at the Chinese Clinical Trial Registry in November 2022 (registry number: ChiCTR2200057286). RESULTS iTBS treatment improved the positive symptoms, negative symptoms, general psychopathology, and WM deficits. Following the iTBS intervention, the active group demonstrated a significant increase in connectivity strengths from the right MFG to the right SPL (p = 0.031) and from the left SPL to the left MFG (p = 0.010) compared to the pre-treatment levels. Additionally, compared to the sham group, the active group displayed a significantly higher connectivity strength from the right MFG to the right SPL (p = 0.042) after iTBS treatment. CONCLUSION All these findings suggest that iTBS targeting the parietal region may influence the resting-state effective connectivity within the frontoparietal network, thereby offering promising therapeutic implications for alleviating the cognitive deficits in SZ.
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Affiliation(s)
- Li Li
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Lina Wang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Han Wu
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Bing Li
- Hebei Provincial Mental Health Center, Baoding, PR China; Hebei Key Laboratory of Major Mental and Behavioral Disorders, Baoding, PR China; The Sixth Clinical Medical College of Hebei University, Baoding, PR China
| | - Weigang Pan
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Wenqing Jin
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Wen Wang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China
| | - Yanping Ren
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China.
| | - Chaomeng Liu
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China.
| | - Xin Ma
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, PR China.
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2
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Yao Y, Zhang S, Wang B, Lin X, Zhao G, Deng H, Chen Y. Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis. Cereb Cortex 2024; 34:bhae267. [PMID: 38960703 DOI: 10.1093/cercor/bhae267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 07/05/2024] Open
Abstract
Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.
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Affiliation(s)
- Yuhao Yao
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Functional & Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
| | - Shufang Zhang
- Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Boyao Wang
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Functional & Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoyong Lin
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Functional & Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
| | - Gaofeng Zhao
- Department of Psychiatry, Shandong Daizhuang Hospital, Jinning, China
| | - Hong Deng
- Mental Health Center, West China Hospital of Sichuan University, Chengdu, China
| | - Ying Chen
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, China
- Functional & Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, China
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3
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Meisenzahl E, Wege N, Stegmüller V, Schulte-Körne G, Greimel E, Dannlowski U, Hahn T, Romer G, Romanos M, Deserno L, Klingele C, Theisen C, Kieckhäfer C, Forstner A, Ruhrmann S, Schultze-Lutter F. Clinical high risk state of major depressive episodes: Assessment of prodromal phase, its occurrence, duration and symptom patterns by the instrument the DEpression Early Prediction-INventory (DEEP-IN). J Affect Disord 2024; 351:403-413. [PMID: 38181843 DOI: 10.1016/j.jad.2023.12.084] [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] [Received: 06/06/2023] [Revised: 12/20/2023] [Accepted: 12/28/2023] [Indexed: 01/07/2024]
Abstract
BACKGROUND To decrease the incidence of major depressive episodes, indicated prevention that targets clinical high-risk individuals with first detectable signs that forecast mental disorder is a highly relevant topic of preventive psychiatry. Still little is known about the prodrome of MDE. The aim of the current study was to identify the occurrence of a clinical high-risk state of depression, its duration and symptom constellation. METHODS Seventy-three patients with a diagnosed affective disorder in partial remission were assessed with our newly developed semi-structured extensive clinical instrument, the DEpression Early Prediction-INventory (DEEP-IN). Within DEEP-IN the course of prodromal symptoms was explored by using a life-chart method. RESULTS The significant majority of patients (93.2 %) reported a prodromal phase. The mean duration was 7.9 months (SD = 12.5). Within the group with an identified prodromal phase, psychopathological (95.6 %) as well as somatic symptoms (88.2 %) were reported. Somatic symptoms showed a moderate-to-strong effect of sex with higher prevalence in females than in males (97.6 % vs 73.1 %; V = 0.370). LIMITATIONS This feasibility study had only a small sample size. CONCLUSIONS The majority of patients with affective disorders reported a clinical prodromal phase with both psychopathological and somatic symptoms that developed months before the onset of the depressive episode. The development of structured instruments for the assessment of depressive risk states is a promising approach for indicated prevention of depression in the future.
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Affiliation(s)
- Eva Meisenzahl
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, LVR Düsseldorf, Düsseldorf, Germany.
| | - Natalia Wege
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, LVR Düsseldorf, Düsseldorf, Germany
| | - Veronika Stegmüller
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, LVR Düsseldorf, Düsseldorf, Germany
| | - Gerd Schulte-Körne
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Ellen Greimel
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Udo Dannlowski
- Institute for Translational Psychiatry, University of Muenster, Muenster, Germany
| | - Tim Hahn
- Institute for Translational Psychiatry, University of Muenster, Muenster, Germany
| | - Georg Romer
- Department of Child Adolescence Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
| | - Marcel Romanos
- Centre of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
| | - Lorenz Deserno
- Centre of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany; Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Neuroimaging Center, Technical University of Dresden, Dresden, Germany
| | - Cosima Klingele
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Christian Theisen
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, LVR Düsseldorf, Düsseldorf, Germany
| | - Carolin Kieckhäfer
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, LVR Düsseldorf, Düsseldorf, Germany
| | - Andreas Forstner
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
| | - Stefan Ruhrmann
- Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany
| | - Frauke Schultze-Lutter
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, LVR Düsseldorf, Düsseldorf, Germany
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4
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Iasevoli F, D’Ambrosio L, Ciccarelli M, Barone A, Gaudieri V, Cocozza S, Pontillo G, Brunetti A, Cuocolo A, de Bartolomeis A, Pappatà S. Altered Patterns of Brain Glucose Metabolism Involve More Extensive and Discrete Cortical Areas in Treatment-resistant Schizophrenia Patients Compared to Responder Patients and Controls: Results From a Head-to-Head 2-[18F]-FDG-PET Study. Schizophr Bull 2023; 49:474-485. [PMID: 36268829 PMCID: PMC10016407 DOI: 10.1093/schbul/sbac147] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND HYPOTHESIS Treatment resistant schizophrenia (TRS) affects almost 30% of patients with schizophrenia and has been considered a different phenotype of the disease. In vivo characterization of brain metabolic patterns associated with treatment response could contribute to elucidate the neurobiological underpinnings of TRS. Here, we used 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) to provide the first head-to-head comparative analysis of cerebral glucose metabolism in TRS patients compared to schizophrenia responder patients (nTRS), and controls. Additionally, we investigated, for the first time, the differences between clozapine responders (Clz-R) and non-responders (Clz-nR). STUDY DESIGN 53 participants underwent FDG-PET studies (41 patients and 12 controls). Response to conventional antipsychotics and to clozapine was evaluated using a standardized prospective procedure based on PANSS score changes. Maps of relative brain glucose metabolism were processed for voxel-based analysis using Statistical Parametric Mapping software. STUDY RESULTS Restricted areas of significant bilateral relative hypometabolism in the superior frontal gyrus characterized TRS compared to nTRS. Moreover, reduced parietal and frontal metabolism was associated with high PANSS disorganization factor scores in TRS (P < .001 voxel level uncorrected, P < .05 cluster level FWE-corrected). Only TRS compared to controls showed significant bilateral prefrontal relative hypometabolism, more extensive in CLZ-nR than in CLZ-R (P < .05 voxel level FWE-corrected). Relative significant hypermetabolism was observed in the temporo-occipital regions in TRS compared to nTRS and controls. CONCLUSIONS These data indicate that, in TRS patients, altered metabolism involved discrete brain regions not found affected in nTRS, possibly indicating a more severe disrupted functional brain network associated with disorganization symptoms.
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Affiliation(s)
- Felice Iasevoli
- Section of Psychiatry, Unit of Treatment Resistant Psychosis, Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Luigi D’Ambrosio
- Section of Psychiatry, Unit of Treatment Resistant Psychosis, Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Mariateresa Ciccarelli
- Section of Psychiatry, Unit of Treatment Resistant Psychosis, Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Annarita Barone
- Section of Psychiatry, Unit of Treatment Resistant Psychosis, Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Valeria Gaudieri
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Sirio Cocozza
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Giuseppe Pontillo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Arturo Brunetti
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Alberto Cuocolo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy
| | - Andrea de Bartolomeis
- Section of Psychiatry, Unit of Treatment Resistant Psychosis, Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
- UNESCO Chair on Health Education and Sustainable Development - University of Naples Federico II, Naples, Italy
| | - Sabina Pappatà
- Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy
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5
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Burgher B, Scott J, Cocchi L, Breakspear M. Longitudinal changes in neural gain and its relationship to cognitive control trajectory in young adults with early psychosis. Transl Psychiatry 2023; 13:77. [PMID: 36864034 PMCID: PMC9981770 DOI: 10.1038/s41398-023-02381-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 02/18/2023] [Accepted: 02/23/2023] [Indexed: 03/04/2023] Open
Abstract
The mixed cognitive outcomes in early psychosis (EP) have important implications for recovery. In this longitudinal study, we asked whether baseline differences in the cognitive control system (CCS) in EP participants would revert toward a normative trajectory seen in healthy controls (HC). Thirty EP and 30 HC undertook functional MRI at baseline using the multi-source interference task-a paradigm that selectively introduces stimulus conflict-and 19 in each group repeated the task at 12 months. Activation of the left superior parietal cortex normalized over time for the EP group, relative to HC, coincident with improvements in reaction time and social-occupational functioning. To examine these group and timepoint differences, we used dynamic causal modeling to infer changes in effective connectivity between regions underlying the MSIT task execution, namely visual, anterior insula, anterior cingulate, and superior parietal cortical regions. To resolve stimulus conflict, EP participants transitioned from an indirect to a direct neuromodulation of sensory input to the anterior insula over timepoints, though not as strongly as HC participants. Stronger direct nonlinear modulation of the anterior insula by the superior parietal cortex at follow-up was associated with improved task performance. Overall, normalization of the CCS through adoption of more direct processing of complex sensory input to the anterior insula, was observed in EP after 12 months of treatment. Such processing of complex sensory input reflects a computational principle called gain control, which appears to track changes in cognitive trajectory within the EP group.
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Affiliation(s)
- Bjorn Burgher
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
| | - James Scott
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
- Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia
| | - Luca Cocchi
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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Friston K. Computational psychiatry: from synapses to sentience. Mol Psychiatry 2023; 28:256-268. [PMID: 36056173 PMCID: PMC7614021 DOI: 10.1038/s41380-022-01743-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 08/08/2022] [Accepted: 08/11/2022] [Indexed: 01/09/2023]
Abstract
This review considers computational psychiatry from a particular viewpoint: namely, a commitment to explaining psychopathology in terms of pathophysiology. It rests on the notion of a generative model as underwriting (i) sentient processing in the brain, and (ii) the scientific process in psychiatry. The story starts with a view of the brain-from cognitive and computational neuroscience-as an organ of inference and prediction. This offers a formal description of neuronal message passing, distributed processing and belief propagation in neuronal networks; and how certain kinds of dysconnection lead to aberrant belief updating and false inference. The dysconnections in question can be read as a pernicious synaptopathy that fits comfortably with formal notions of how we-or our brains-encode uncertainty or its complement, precision. It then considers how the ensuing process theories are tested empirically, with an emphasis on the computational modelling of neuronal circuits and synaptic gain control that mediates attentional set, active inference, learning and planning. The opportunities afforded by this sort of modelling are considered in light of in silico experiments; namely, computational neuropsychology, computational phenotyping and the promises of a computational nosology for psychiatry. The resulting survey of computational approaches is not scholarly or exhaustive. Rather, its aim is to review a theoretical narrative that is emerging across subdisciplines within psychiatry and empirical scales of investigation. These range from epilepsy research to neurodegenerative disorders; from post-traumatic stress disorder to the management of chronic pain, from schizophrenia to functional medical symptoms.
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Affiliation(s)
- Karl Friston
- Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London, WC1N 3AR, UK.
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7
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Gifford G, Crossley N, Morgan S, Kempton MJ, Dazzan P, Modinos G, Azis M, Samson C, Bonoldi I, Quinn B, Smart SE, Antoniades M, Bossong MG, Broome MR, Perez J, Howes OD, Stone JM, Allen P, Grace AA, McGuire P. Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis. Hum Brain Mapp 2021; 42:439-451. [PMID: 33048435 PMCID: PMC7775992 DOI: 10.1002/hbm.25235] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 08/28/2020] [Accepted: 09/29/2020] [Indexed: 01/22/2023] Open
Abstract
The ability to identify biomarkers of psychosis risk is essential in defining effective preventive measures to potentially circumvent the transition to psychosis. Using samples of people at clinical high risk for psychosis (CHR) and Healthy controls (HC) who were administered a task fMRI paradigm, we used a framework for labelling time windows of fMRI scans as 'integrated' FC networks to provide a granular representation of functional connectivity (FC). Periods of integration were defined using the 'cartographic profile' of time windows and k-means clustering, and sub-network discovery was carried out using Network Based Statistics (NBS). There were no network differences between CHR and HC groups. Within the CHR group, using integrated FC networks, we identified a sub-network negatively associated with longitudinal changes in the severity of psychotic symptoms. This sub-network comprised brain areas implicated in bottom-up sensory processing and in integration with motor control, suggesting it may be related to the demands of the fMRI task. These data suggest that extracting integrated FC networks may be useful in the investigation of biomarkers of psychosis risk.
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Affiliation(s)
- George Gifford
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Nicolas Crossley
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Sarah Morgan
- Department of Psychiatry, University of Cambridge, Cambridge, UK.,The Alan Turing Institute, London, UK
| | - Matthew J Kempton
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Paola Dazzan
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,South London and Maudsley NHS Trust, Maudsley Hospital, London, UK
| | - Gemma Modinos
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Matilda Azis
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Carly Samson
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Ilaria Bonoldi
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,South London and Maudsley NHS Trust, Maudsley Hospital, London, UK
| | - Beverly Quinn
- CAMEO Early Intervention in Psychosis Service, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Sophie E Smart
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - Mathilde Antoniades
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Psychiatry, Icahn Medical School, Mt Sinai Hospital, New York, New York, USA
| | - Matthijs G Bossong
- Department of Psychiatry, UMC Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | - Matthew R Broome
- Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, UK
| | - Jesus Perez
- CAMEO Early Intervention in Psychosis Service, Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Oliver D Howes
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,South London and Maudsley NHS Trust, Maudsley Hospital, London, UK
| | - James M Stone
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,South London and Maudsley NHS Trust, Maudsley Hospital, London, UK.,Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Paul Allen
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Department of Psychology, University of Roehampton, London, UK
| | - Anthony A Grace
- Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Philip McGuire
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,South London and Maudsley NHS Trust, Maudsley Hospital, London, UK
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8
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Andreou C, Borgwardt S. Structural and functional imaging markers for susceptibility to psychosis. Mol Psychiatry 2020; 25:2773-2785. [PMID: 32066828 PMCID: PMC7577836 DOI: 10.1038/s41380-020-0679-7] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 01/15/2020] [Accepted: 01/31/2020] [Indexed: 12/21/2022]
Abstract
The introduction of clinical criteria for the operationalization of psychosis high risk provided a basis for early detection and treatment of vulnerable individuals. However, about two-thirds of people meeting clinical high-risk (CHR) criteria will never develop a psychotic disorder. In the effort to increase prognostic precision, structural and functional neuroimaging have received growing attention as a potentially useful resource in the prediction of psychotic transition in CHR patients. The present review summarizes current research on neuroimaging biomarkers in the CHR state, with a particular focus on their prognostic utility and limitations. Large, multimodal/multicenter studies are warranted to address issues important for clinical applicability such as generalizability and replicability, standardization of clinical definitions and neuroimaging methods, and consideration of contextual factors (e.g., age, comorbidity).
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Affiliation(s)
- Christina Andreou
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany
- Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
| | - Stefan Borgwardt
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.
- Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
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9
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Metzak PD, Devoe DJ, Iwaschuk A, Braun A, Addington J. Brain changes associated with negative symptoms in clinical high risk for psychosis: A systematic review. Neurosci Biobehav Rev 2020; 118:367-383. [PMID: 32768487 DOI: 10.1016/j.neubiorev.2020.07.041] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 07/21/2020] [Accepted: 07/31/2020] [Indexed: 02/05/2023]
Abstract
The negative symptoms of schizophrenia are linked to poorer functional outcomes and decreases in quality of life, and are often the first to develop in individuals who are at clinical high risk (CHR) for psychosis. However, the accompanying neurobiological changes are poorly understood. Therefore, we conducted a systematic review of the studies that have examined the brain metrics associated with negative symptoms in those at CHR. Electronic databases were searched from inception to August 2019. Studies were selected if they mentioned negative symptoms in youth at CHR for psychosis, and brain imaging. Of 261 citations, 43 studies with 2144 CHR participants met inclusion criteria. Too few studies were focused on the same brain regions using similar neuroimaging methods to perform a meta-analysis, however, the results of this systematic review suggest a relationship between negative symptom increases and decreases in grey matter. The paucity of studies linking changes in brain structure and function with negative symptoms in those at CHR suggests that future work should focus on examining these relationships.
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Affiliation(s)
- Paul D Metzak
- Hotchkiss Brain Institute, Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada; Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
| | - Daniel J Devoe
- Hotchkiss Brain Institute, Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada; Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
| | - Amanda Iwaschuk
- Hotchkiss Brain Institute, Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada; Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
| | - Amy Braun
- Hotchkiss Brain Institute, Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada; Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
| | - Jean Addington
- Hotchkiss Brain Institute, Department of Psychiatry, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada; Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
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10
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O'Brien KJ, Barch DM, Kandala S, Karcher NR. Examining Specificity of Neural Correlates of Childhood Psychotic-like Experiences During an Emotional n-Back Task. BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2020; 5:580-590. [PMID: 32354687 DOI: 10.1016/j.bpsc.2020.02.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 02/25/2020] [Accepted: 02/25/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder in adulthood, highlighting the importance of identifying neural correlates of childhood PLEs. Furthermore, impairment of cognitive functions, such as working memory and emotion regulation, has also been linked to psychosis risk as well as to disruptions in several brain regions. However, impairments in these domains have also been linked to other disorders, including depression. Therefore, the aim of the current study was to examine whether neural impairments in regions associated with working memory and implicit emotion regulation impairments are specific to PLEs versus depression. METHODS The current study used an emotional n-back task to examine the relationship between childhood PLEs and neural activation of regions involved in both working memory and implicit emotion regulation using data from 8805 9- to 11-year-olds in the Adolescent Brain Cognitive Development (ABCD) Study 2.0 release. To examine specificity, we also analyzed associations with depressive symptoms. RESULTS Our results indicated that increased PLEs during middle childhood were associated with decreased activation of the dorsolateral prefrontal cortex, striatum, and pallidum during trials requiring working memory. In contrast, increased activation of the parahippocampus, caudate, nucleus accumbens, and rostral anterior cingulate during face-viewing trials was associated with increased depressive symptoms. CONCLUSIONS These results support the dimensional view of psychosis across the lifespan, providing evidence that neural correlates of PLEs, such as decreased activation during working memory, are present during middle childhood. Furthermore, these correlates are specific to psychotic-like symptoms as compared with depressive symptoms.
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Affiliation(s)
- Kathleen J O'Brien
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
| | - Deanna M Barch
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Department of Psychology, Washington University, St. Louis, Missouri
| | - Sridhar Kandala
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
| | - Nicole R Karcher
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
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11
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Impaired action self-monitoring and cognitive confidence among ultra-high risk for psychosis and first-episode psychosis patients. Eur Psychiatry 2020; 47:67-75. [DOI: 10.1016/j.eurpsy.2017.09.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Revised: 08/29/2017] [Accepted: 09/07/2017] [Indexed: 01/06/2023] Open
Abstract
AbstractBackgroundSelf-monitoring biases and overconfidence in incorrect judgments have been suggested as playing a role in schizophrenia spectrum disorders. Little is known about whether self-monitoring biases may contribute to early risk factors for psychosis. In this study, action self-monitoring (i.e., discrimination between imagined and performed actions) was investigated, along with confidence in judgments among ultra-high risk (UHR) for psychosis individuals and first-episode psychosis (FEP) patients.MethodsThirty-six UHR for psychosis individuals, 25 FEP patients and 33 healthy controls (CON) participated in the study. Participants were assessed with the Action memory task. Simple actions were presented to participants verbally or non-verbally. Some actions were required to be physically performed and others were imagined. Participants were asked whether the action was presented verbally or non-verbally (action presentation type discrimination), and whether the action was performed or imagined (self-monitoring). Confidence self-ratings related to self-monitoring responses were obtained.ResultsThe analysis of self-monitoring revealed that both UHR and FEP groups misattributed imagined actions as being performed (i.e., self-monitoring errors) significantly more often than the CON group. There were no differences regarding performed actions as being imagined. UHR and FEP groups made their false responses with higher confidence in their judgments than the CON group. There were no group differences regarding discrimination between the types of actions presented (verbal vs non-verbal).ConclusionsA specific type of self-monitoring bias (i.e., misattributing imagined actions with performed actions), accompanied by high confidence in this judgment, may be a risk factor for the subsequent development of a psychotic disorder.
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12
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Diaconescu AO, Hauke DJ, Borgwardt S. Models of persecutory delusions: a mechanistic insight into the early stages of psychosis. Mol Psychiatry 2019; 24:1258-1267. [PMID: 31076646 PMCID: PMC6756090 DOI: 10.1038/s41380-019-0427-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 02/27/2019] [Accepted: 04/11/2019] [Indexed: 12/16/2022]
Abstract
Identifying robust markers for predicting the onset of psychosis has been a key challenge for early detection research. Persecutory delusions are core symptoms of psychosis, and social cognition is particularly impaired in first-episode psychosis patients and individuals at risk for developing psychosis. Here, we propose new avenues for translation provided by hierarchical Bayesian models of behaviour and neuroimaging data applied in the context of social learning to target persecutory delusions. As it comprises a mechanistic model embedded in neurophysiology, the findings of this approach may shed light onto inference and neurobiological causes of transition to psychosis.
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Affiliation(s)
- Andreea Oliviana Diaconescu
- Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich & Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.
| | - Daniel Jonas Hauke
- Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
- Department of Mathematics and Computer Science, University of Basel, Basel, Switzerland
| | - Stefan Borgwardt
- Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
- Department of Psychosis Studies PO63, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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13
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Tomyshev AS, Lebedeva IS, Akhadov TA, Omelchenko MA, Rumyantsev AO, Kaleda VG. Alterations in white matter microstructure and cortical thickness in individuals at ultra-high risk of psychosis: A multimodal tractography and surface-based morphometry study. Psychiatry Res Neuroimaging 2019; 289:26-36. [PMID: 31132567 DOI: 10.1016/j.pscychresns.2019.05.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 02/24/2019] [Accepted: 05/08/2019] [Indexed: 12/11/2022]
Abstract
There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects.
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Affiliation(s)
- Alexander S Tomyshev
- Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, 34 Kashirskoe shosse, 115522 Moscow, Russia.
| | - Irina S Lebedeva
- Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, 34 Kashirskoe shosse, 115522 Moscow, Russia
| | - Tolibdzhon A Akhadov
- Department of Radiology, Children's Clinical and Research Institute of Emergency Surgery and Trauma, Moscow, Russia
| | - Maria A Omelchenko
- Department of Endogenous Mental Disorders, Mental Health Research Center, Moscow, Russia
| | - Andrey O Rumyantsev
- Department of Endogenous Mental Disorders, Mental Health Research Center, Moscow, Russia
| | - Vasiliy G Kaleda
- Department of Endogenous Mental Disorders, Mental Health Research Center, Moscow, Russia
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14
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Fukuda Y, Katthagen T, Deserno L, Shayegan L, Kaminski J, Heinz A, Schlagenhauf F. Reduced parietofrontal effective connectivity during a working-memory task in people with high delusional ideation. J Psychiatry Neurosci 2019; 44:195-204. [PMID: 30657658 PMCID: PMC6488486 DOI: 10.1503/jpn.180043] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Working-memory impairment is a core cognitive dysfunction in people with schizophrenia and people at mental high risk. Recent imaging studies on working memory have suggested that abnormalities in prefrontal activation and in connectivity between the frontal and parietal regions could be neural underpinnings of the different stages of psychosis. However, it remains to be explored whether comparable alterations are present in people with subclinical levels of psychosis, as experienced by a small proportion of the general population who neither seek help nor show constraints in daily functioning. METHODS We compared 24 people with subclinical high delusional ideation and 24 people with low delusional ideation. Both groups performed an n-back working-memory task during functional magnetic resonance imaging. We characterized frontoparietal effective connectivity using dynamic causal modelling. RESULTS Compared to people who had low delusional ideation, people with high delusional ideation showed a significant increase in dorsolateral prefrontal activation during the working-memory task, as well as reduced working-memory-dependent parietofrontal effective connectivity in the left hemisphere. Group differences were not evident at the behavioural level. LIMITATIONS The current experimental design did not distinguish among the working-memory subprocesses; it remains unexplored whether differences in connectivity exist at that level. CONCLUSION These findings suggest that alterations in the working-memory network are also present in a nonclinical population with psychotic experiences who do not display cognitive deficits. They also suggest that alterations in working-memory-dependent connectivity show a putative continuity along the spectrum of psychotic symptoms.
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Affiliation(s)
- Yu Fukuda
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
| | - Teresa Katthagen
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
| | - Lorenz Deserno
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
| | - Leila Shayegan
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
| | - Jakob Kaminski
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
| | - Andreas Heinz
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
| | - Florian Schlagenhauf
- From the Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany (Fukuda, Katthagen, Kaminski, Heinz, Schlagenhauf); the Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany (Deserno); Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Deserno, Kaminski, Schlagenhauf); the Columbia University College of Physicians and Surgeons, New York, NY (Shayegan); and the Berlin Institute of Health, Berlin, Germany (Kaminski)
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15
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Structural and functional alterations in the brain during working memory in medication-naïve patients at clinical high-risk for psychosis. PLoS One 2018; 13:e0196289. [PMID: 29742121 PMCID: PMC5942777 DOI: 10.1371/journal.pone.0196289] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 04/10/2018] [Indexed: 12/18/2022] Open
Abstract
Several previous studies suggest that clinical high risk for psychosis (CHR) is associated with prefrontal functional abnormalities and more widespread reduced grey matter in prefrontal, temporal and parietal areas. We investigated neural correlates to CHR in medication-naïve patients. 41 CHR patients and 37 healthy controls were examined with 1.5 Tesla MRI, yielding functional scans while performing an N-back task and structural T1-weighted brain images. Functional and structural data underwent automated preprocessing steps in SPM and Freesurfer, correspondingly. The groups were compared employing mass-univariate strategy within the generalized linear modelling framework. CHR demonstrated reduced suppression of the medial temporal lobe (MTL) regions during n-back task. We also found that, consistent with previous findings, CHR subjects demonstrated thinning in prefrontal, cingulate, insular and inferior temporal areas, as well as reduced hippocampal volumes. The present findings add to the growing evidence of specific structural and functional abnormalities in the brain as potential neuroimaging markers of psychosis vulnerability.
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16
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Clark SV, Mittal VA, Bernard JA, Ahmadi A, King TZ, Turner JA. Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders. Schizophr Res 2018; 193:244-250. [PMID: 28688741 PMCID: PMC5756141 DOI: 10.1016/j.schres.2017.06.043] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 06/09/2017] [Accepted: 06/22/2017] [Indexed: 12/22/2022]
Abstract
Impaired clinical insight (CI) is a common symptom of psychotic disorders and a promising treatment target. However, to date, our understanding of how variability in CI is tied to underlying brain dysfunction in the clinical high-risk period is limited. Developing a stronger conception of this link will be a vital first step for efforts to determine if CI can serve as a useful prognostic indicator. The current study investigated whether variability in CI is related to major brain networks in adolescents and young adults at ultra high-risk (UHR) of developing psychosis. Thirty-five UHR youth were administered structured clinical interviews as well as an assessment for CI and underwent resting-state magnetic resonance imaging scans. Functional connectivity was calculated in the default mode network (DMN) and fronto-parietal network (FPN), two major networks that are dysfunctional in psychosis and are hypothesized to affect insight. Greater DMN connectivity between the posterior cingulate/precuneus and ventromedial prefrontal cortex (DMN) was related to poorer CI (R2=0.399). There were no significant relationships between insight and the FPN. This is the first study to relate a major brain network to clinical insight before the onset of psychosis. Findings are consistent with evidence if a hyperconnected DMN in schizophrenia and UHR, and similar to a previous study of insight and connectivity in schizophrenia. Results suggest that a strongly connected DMN may be related to poor self-awareness of subthreshold psychotic symptoms in UHR adolescents and young adults.
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Affiliation(s)
- Sarah V Clark
- Georgia State University, Department of Psychology, Atlanta, GA, USA.
| | - Vijay A Mittal
- Northwestern University, Department of Psychology, Evanston, Chicago, IL, USA; Northwestern University, Department of Psychiatry, Evanston, Chicago, IL, USA; Northwestern University, Institute for Policy Research, Evanston, Chicago, IL, USA; Northwestern University, Department of Medical Social Sciences, Evanston, Chicago, IL, USA
| | - Jessica A Bernard
- Texas A&M University, Department of Psychology, College Station, TX, USA
| | - Aral Ahmadi
- Georgia State University, Department of Psychology, Atlanta, GA, USA
| | - Tricia Z King
- Georgia State University, Department of Psychology, Atlanta, GA, USA
| | - Jessica A Turner
- Georgia State University, Department of Psychology, Atlanta, GA, USA; The Mind Research Network, Albuquerque, NM, USA
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Pratt JA, Morris B, Dawson N. Deconstructing Schizophrenia: Advances in Preclinical Models for Biomarker Identification. Curr Top Behav Neurosci 2018; 40:295-323. [PMID: 29721851 DOI: 10.1007/7854_2018_48] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Schizophrenia is considered to develop as a consequence of genetic and environmental factors impacting on brain neural systems and circuits during vulnerable neurodevelopmental periods, thereby resulting in symptoms in early adulthood. Understanding of the impact of schizophrenia risk factors on brain biology and behaviour can help in identifying biologically relevant pathways that are attractive for informing clinical studies and biomarker development. In this chapter, we emphasize the importance of adopting a reciprocal forward and reverse translation approach that is iteratively updated when additional new information is gained, either preclinically or clinically, for offering the greatest opportunity for discovering panels of biomarkers for the diagnosis, prognosis and treatment of schizophrenia. Importantly, biomarkers for identifying those at risk may inform early intervention strategies prior to the development of schizophrenia.Given the emerging nature of this approach in the field, this review will highlight recent research of preclinical biomarkers in schizophrenia that show the most promise for informing clinical needs with an emphasis on relevant imaging, electrophysiological, cognitive behavioural and biochemical modalities. The implementation of this reciprocal translational approach is exemplified firstly by the production and characterization of preclinical models based on the glutamate hypofunction hypothesis, genetic and environmental risk factors for schizophrenia (reverse translation), and then the recent clinical recognition of the thalamic reticular thalamus (TRN) as an important locus of brain dysfunction in schizophrenia as informed by preclinical findings (forward translation).
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Affiliation(s)
- Judith A Pratt
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
| | - Brian Morris
- Institute of Neuroscience and Psychology, College of Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Neil Dawson
- Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK
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18
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Dauvermann MR, Moorhead TW, Watson AR, Duff B, Romaniuk L, Hall J, Roberts N, Lee GL, Hughes ZA, Brandon NJ, Whitcher B, Blackwood DH, McIntosh AM, Lawrie SM. Verbal working memory and functional large-scale networks in schizophrenia. Psychiatry Res Neuroimaging 2017; 270:86-96. [PMID: 29111478 DOI: 10.1016/j.pscychresns.2017.10.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Revised: 09/16/2017] [Accepted: 10/20/2017] [Indexed: 12/17/2022]
Abstract
The aim of this study was to test whether bilinear and nonlinear effective connectivity (EC) measures of working memory fMRI data can differentiate between patients with schizophrenia (SZ) and healthy controls (HC). We applied bilinear and nonlinear Dynamic Causal Modeling (DCM) for the analysis of verbal working memory in 16 SZ and 21 HC. The connection strengths with nonlinear modulation between the dorsolateral prefrontal cortex (DLPFC) and the ventral tegmental area/substantia nigra (VTA/SN) were evaluated. We used Bayesian Model Selection at the group and family levels to compare the optimal bilinear and nonlinear models. Bayesian Model Averaging was used to assess the connection strengths with nonlinear modulation. The DCM analyses revealed that SZ and HC used different bilinear networks despite comparable behavioral performance. In addition, the connection strengths with nonlinear modulation between the DLPFC and the VTA/SN area showed differences between SZ and HC. The adoption of different functional networks in SZ and HC indicated neurobiological alterations underlying working memory performance, including different connection strengths with nonlinear modulation between the DLPFC and the VTA/SN area. These novel findings may increase our understanding of connectivity in working memory in schizophrenia.
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Affiliation(s)
- Maria R Dauvermann
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK; School of Psychology, National University of Ireland Galway, University Road, Galway, Ireland; McGovern Institute for Brain Research, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, MA 02139, USA.
| | - Thomas Wj Moorhead
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
| | - Andrew R Watson
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
| | - Barbara Duff
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
| | - Liana Romaniuk
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
| | - Jeremy Hall
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK; Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
| | - Neil Roberts
- Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Graham L Lee
- McGovern Institute for Brain Research, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, MA 02139, USA
| | - Zoë A Hughes
- Neuroscience Research Unit, Pfizer Inc., Cambridge, MA, USA
| | - Nicholas J Brandon
- Neuroscience Research Unit, Pfizer Inc., Cambridge, MA, USA; IMED Neuroscience Unit, AstraZeneca, Waltham, MA, USA
| | - Brandon Whitcher
- Clinical and Translational Imaging, Pfizer Inc., Cambridge, MA, USA
| | - Douglas Hr Blackwood
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
| | - Andrew M McIntosh
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
| | - Stephen M Lawrie
- Division of Psychiatry, Royal Edinburgh Hospital, Morningside Park, University of Edinburgh, Edinburgh EH10 5HF, UK
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Jung K, Friston KJ, Pae C, Choi HH, Tak S, Choi YK, Park B, Park CA, Cheong C, Park HJ. Effective connectivity during working memory and resting states: A DCM study. Neuroimage 2017; 169:485-495. [PMID: 29284140 DOI: 10.1016/j.neuroimage.2017.12.067] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 12/14/2017] [Accepted: 12/20/2017] [Indexed: 01/05/2023] Open
Abstract
Although the relationship between resting-state functional connectivity and task-related activity has been addressed, the relationship between task and resting-state directed or effective connectivity - and its behavioral concomitants - remains elusive. We evaluated effective connectivity under an N-back working memory task in 24 participants using stochastic dynamic causal modelling (DCM) of 7 T fMRI data. We repeated the analysis using resting-state data, from the same subjects, to model connectivity among the same brain regions engaged by the N-back task. This allowed us to: (i) examine the relationship between intrinsic (task-independent) effective connectivity during resting (Arest) and task states (Atask), (ii) cluster phenotypes of task-related changes in effective connectivity (Btask) across participants, (iii) identify edges (Btask) showing high inter-individual effective connectivity differences and (iv) associate reaction times with the similarity between Btask and Arest in these edges. We found a strong correlation between Arest and Atask over subjects but a marked difference between Btask and Arest. We further observed a strong clustering of individuals in terms of Btask, which was not apparent in Arest. The task-related effective connectivity Btask varied highly in the edges from the parietal to the frontal lobes across individuals, so the three groups were clustered mainly by the effective connectivity within these networks. The similarity between Btask and Arest at the edges from the parietal to the frontal lobes was positively correlated with 2-back reaction times. This result implies that a greater change in context-sensitive coupling - from resting-state connectivity - is associated with faster reaction times. In summary, task-dependent connectivity endows resting-state connectivity with a context sensitivity, which predicts the speed of information processing during the N-back task.
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Affiliation(s)
- Kyesam Jung
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea; Center for Systems and Translational Brain Sciences, Institute of Human Complexity and Systems Science, Yonsei University, Seoul, South Korea
| | - Karl J Friston
- The Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom
| | - Chongwon Pae
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea; Center for Systems and Translational Brain Sciences, Institute of Human Complexity and Systems Science, Yonsei University, Seoul, South Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Hanseul H Choi
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea; Center for Systems and Translational Brain Sciences, Institute of Human Complexity and Systems Science, Yonsei University, Seoul, South Korea
| | - Sungho Tak
- Bioimaging Research Team, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk-do, South Korea
| | - Yoon Kyoung Choi
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea; Center for Systems and Translational Brain Sciences, Institute of Human Complexity and Systems Science, Yonsei University, Seoul, South Korea; Department of Cognitive Science, Yonsei University, Seoul, South Korea
| | - Bumhee Park
- Center for Systems and Translational Brain Sciences, Institute of Human Complexity and Systems Science, Yonsei University, Seoul, South Korea; Department of Statistics, Hankuk University of Foreign Studies, Yong-In, South Korea
| | - Chan-A Park
- Bioimaging Research Team, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk-do, South Korea
| | - Chaejoon Cheong
- Bioimaging Research Team, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk-do, South Korea; Department of Bioconvergence Analysis, Korea Basic Science Institute, Cheongju-si, Chungcheongbuk-do, South Korea
| | - Hae-Jeong Park
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea; Center for Systems and Translational Brain Sciences, Institute of Human Complexity and Systems Science, Yonsei University, Seoul, South Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; Department of Cognitive Science, Yonsei University, Seoul, South Korea.
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20
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Zhou Y, Zeidman P, Wu S, Razi A, Chen C, Yang L, Zou J, Wang G, Wang H, Friston KJ. Altered intrinsic and extrinsic connectivity in schizophrenia. NEUROIMAGE-CLINICAL 2017; 17:704-716. [PMID: 29264112 PMCID: PMC5726753 DOI: 10.1016/j.nicl.2017.12.006] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 09/25/2017] [Accepted: 12/03/2017] [Indexed: 01/12/2023]
Abstract
Schizophrenia is a disorder characterized by functional dysconnectivity among distributed brain regions. However, it is unclear how causal influences among large-scale brain networks are disrupted in schizophrenia. In this study, we used dynamic causal modeling (DCM) to assess the hypothesis that there is aberrant directed (effective) connectivity within and between three key large-scale brain networks (the dorsal attention network, the salience network and the default mode network) in schizophrenia during a working memory task. Functional MRI data during an n-back task from 40 patients with schizophrenia and 62 healthy controls were analyzed. Using hierarchical modeling of between-subject effects in DCM with Parametric Empirical Bayes, we found that intrinsic (within-region) and extrinsic (between-region) effective connectivity involving prefrontal regions were abnormal in schizophrenia. Specifically, in patients (i) inhibitory self-connections in prefrontal regions of the dorsal attention network were decreased across task conditions; (ii) extrinsic connectivity between regions of the default mode network was increased; specifically, from posterior cingulate cortex to the medial prefrontal cortex; (iii) between-network extrinsic connections involving the prefrontal cortex were altered; (iv) connections within networks and between networks were correlated with the severity of clinical symptoms and impaired cognition beyond working memory. In short, this study revealed the predominance of reduced synaptic efficacy of prefrontal efferents and afferents in the pathophysiology of schizophrenia.
A first use of hierarchical modeling of effective connectivity to characterize large-scale networks in schizophrenia. Intrinsic and extrinsic effective connectivity involving prefrontal regions were abnormal in schizophrenia. Diagnostic connections could predict the severity of clinical symptoms and cognition in schizophrenia.
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Affiliation(s)
- Yuan Zhou
- CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China; Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101,China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China; The Wellcome Trust Centre for Neuroimaging, University College London, Queen Square, London WC1N 3BG, UK.
| | - Peter Zeidman
- The Wellcome Trust Centre for Neuroimaging, University College London, Queen Square, London WC1N 3BG, UK
| | - Shihao Wu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Adeel Razi
- The Wellcome Trust Centre for Neuroimaging, University College London, Queen Square, London WC1N 3BG, UK; Department of Electronic Engineering, NED University of Engineering and Technology, Karachi, Pakistan
| | - Cheng Chen
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Liuqing Yang
- CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jilin Zou
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Gaohua Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Huiling Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
| | - Karl J Friston
- The Wellcome Trust Centre for Neuroimaging, University College London, Queen Square, London WC1N 3BG, UK
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21
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Sasabayashi D, Takayanagi Y, Takahashi T, Koike S, Yamasue H, Katagiri N, Sakuma A, Obara C, Nakamura M, Furuichi A, Kido M, Nishikawa Y, Noguchi K, Matsumoto K, Mizuno M, Kasai K, Suzuki M. Increased Occipital Gyrification and Development of Psychotic Disorders in Individuals With an At-Risk Mental State: A Multicenter Study. Biol Psychiatry 2017; 82:737-745. [PMID: 28709499 DOI: 10.1016/j.biopsych.2017.05.018] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 05/17/2017] [Accepted: 05/18/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Anomalies of brain gyrification have been reported in schizophrenia, possibly reflecting its neurodevelopmental pathology. However, it remains elusive whether individuals at risk for psychotic disorders exhibit deviated gyrification patterns, and whether such findings, if present, are predictive of transition to psychotic disorders. METHODS This multicenter magnetic resonance imaging study investigated brain gyrification and its relationship to later transition to psychotic disorders in a large sample of at-risk mental state (ARMS) individuals. T1-weighted magnetic resonance imaging scans were obtained from 104 ARMS individuals, of whom 21 (20.2%) exhibited the transition to psychotic disorders during clinical follow-up (mean = 4.9 years, SD = 2.6 years), and 104 healthy control subjects at 4 different sites. The local gyrification index (LGI) of the entire cortex was compared across the groups using FreeSurfer software. RESULTS Compared with the control subjects, ARMS individuals showed a significantly higher LGI in widespread cortical areas, including the bilateral frontal, temporal, parietal, and occipital regions, which was partly associated with prodromal symptomatology. ARMS individuals who exhibited the transition to psychotic disorders showed a significantly higher LGI in the left occipital region compared with individuals without transition. CONCLUSIONS These findings suggested that increased LGI in diverse cortical regions might represent vulnerability to psychopathology, while increased LGI in the left occipital cortex might be related to subsequent manifestation of florid psychotic disorders as a possible surrogate marker.
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Affiliation(s)
- Daiki Sasabayashi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
| | - Yoichiro Takayanagi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Tsutomu Takahashi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Shinsuke Koike
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidenori Yamasue
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Naoyuki Katagiri
- Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan
| | - Atsushi Sakuma
- Department of Psychiatry, Tohoku University Hospital, Sendai, Japan
| | - Chika Obara
- Department of Psychiatry, Tohoku University Hospital, Sendai, Japan
| | - Mihoko Nakamura
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Atsushi Furuichi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Mikio Kido
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Yumiko Nishikawa
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Kyo Noguchi
- Department of Radiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Kazunori Matsumoto
- Department of Psychiatry, Tohoku University Hospital, Sendai, Japan; Department of Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Masafumi Mizuno
- Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan
| | - Kiyoto Kasai
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Michio Suzuki
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
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22
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Grassi S, Orsenigo G, Serati M, Caletti E, Altamura AC, Buoli M. Cognitive correlates of neuroimaging abnormalities in the onset of schizophrenia: A case report. World J Psychiatry 2017; 7:128-132. [PMID: 28713691 PMCID: PMC5491478 DOI: 10.5498/wjp.v7.i2.128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Revised: 04/23/2017] [Accepted: 05/15/2017] [Indexed: 02/05/2023] Open
Abstract
Increasing evidence shows that cognitive impairment and brain abnormalities can appear early in the first episodes of schizophrenia, but it is currently debated how brain changes can correlate with clinical presentation of schizophrenic patients. Of note, this report describes the case of a young schizophrenic male presenting parietal magnetic resonance/positron emission tomography abnormalities and cognitive impairment, documented by specific neuropsychological tests. In our knowledge only few studies have investigated if neuropsychological abnormalities could be concomitant with both structural and functional neuroimaging. This case shows that impairment in specific cognitive domains is associated with structural/functional brain abnormalities in the corresponding brain areas (frontal and parietal lobes), supporting the hypothesis of disconnectivity, involving a failure to integrate anatomical and functional pathways. Future research would define the role of cognitive impairment and neurodegeneration in psychiatric nosography and, in particular, their role in the early phases of illness and long-term outcome of schizophrenic patients.
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23
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Díez Á, Ranlund S, Pinotsis D, Calafato S, Shaikh M, Hall MH, Walshe M, Nevado Á, Friston KJ, Adams RA, Bramon E. Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives. Hum Brain Mapp 2017; 38:3262-3276. [PMID: 28345275 DOI: 10.1002/hbm.23588] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 03/14/2017] [Accepted: 03/15/2017] [Indexed: 01/29/2023] Open
Abstract
The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Álvaro Díez
- Division of Psychiatry, University College London, London, United Kingdom.,Department of Basic Psychology II - Cognitive processes, Faculty of Psychology, Complutense University of Madrid, Madrid, Spain.,Laboratory of Cognitive and Computational Neuroscience - Centre for Biomedical Technology (CTB), Complutense University and Technical University of Madrid, Madrid, Spain
| | - Siri Ranlund
- Division of Psychiatry, University College London, London, United Kingdom.,Psychology & Neuroscience - King's College London, Institute of Psychiatry, London, United Kingdom
| | - Dimitris Pinotsis
- The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom.,The Picower Institute for Learning & Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts
| | - Stella Calafato
- Division of Psychiatry, University College London, London, United Kingdom
| | - Madiha Shaikh
- North East London NHS Foundation Trust, London, United Kingdom.,Psychology & Neuroscience - King's College London, Institute of Psychiatry, London, United Kingdom
| | - Mei-Hua Hall
- Psychosis Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts
| | - Muriel Walshe
- Division of Psychiatry, University College London, London, United Kingdom.,Psychology & Neuroscience - King's College London, Institute of Psychiatry, London, United Kingdom
| | - Ángel Nevado
- Department of Basic Psychology II - Cognitive processes, Faculty of Psychology, Complutense University of Madrid, Madrid, Spain.,Laboratory of Cognitive and Computational Neuroscience - Centre for Biomedical Technology (CTB), Complutense University and Technical University of Madrid, Madrid, Spain
| | - Karl J Friston
- The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom
| | - Rick A Adams
- Division of Psychiatry, University College London, London, United Kingdom.,Institute of Cognitive Neuroscience, University College London, London, United Kingdom
| | - Elvira Bramon
- Division of Psychiatry, University College London, London, United Kingdom.,Psychology & Neuroscience - King's College London, Institute of Psychiatry, London, United Kingdom.,Institute of Cognitive Neuroscience, University College London, London, United Kingdom
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24
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Del Casale A, Kotzalidis GD, Rapinesi C, Sorice S, Girardi N, Ferracuti S, Girardi P. Functional Magnetic Resonance Imaging Correlates of First-Episode Psychoses during Attentional and Memory Task Performance. Neuropsychobiology 2017; 74:22-31. [PMID: 27698323 DOI: 10.1159/000448620] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 07/21/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND The nature of the alteration of the response to cognitive tasks in first-episode psychosis (FEP) still awaits clarification. We used activation likelihood estimation, an increasingly used method in evaluating normal and pathological brain function, to identify activation changes in functional magnetic resonance imaging (fMRI) studies of FEP during attentional and memory tasks. METHODS We included 11 peer-reviewed fMRI studies assessing FEP patients versus healthy controls (HCs) during performance of attentional and memory tasks. RESULTS Our database comprised 290 patients with FEP, matched with 316 HCs. Between-group analyses showed that HCs, compared to FEP patients, exhibited hyperactivation of the right middle frontal gyrus (Brodmann area, BA, 9), right inferior parietal lobule (BA 40), and right insula (BA 13) during attentional task performances and hyperactivation of the left insula (BA 13) during memory task performances. CONCLUSIONS Right frontal, parietal, and insular dysfunction during attentional task performance and left insular dysfunction during memory task performance are significant neural functional FEP correlates.
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Affiliation(s)
- Antonio Del Casale
- Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), School of Medicine and Psychology, Sapienza University, Rome, Italy
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25
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Friston K, Brown HR, Siemerkus J, Stephan KE. The dysconnection hypothesis (2016). Schizophr Res 2016; 176:83-94. [PMID: 27450778 PMCID: PMC5147460 DOI: 10.1016/j.schres.2016.07.014] [Citation(s) in RCA: 394] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 07/06/2016] [Accepted: 07/15/2016] [Indexed: 02/06/2023]
Abstract
Twenty years have passed since the dysconnection hypothesis was first proposed (Friston and Frith, 1995; Weinberger, 1993). In that time, neuroscience has witnessed tremendous advances: we now live in a world of non-invasive neuroanatomy, computational neuroimaging and the Bayesian brain. The genomics era has come and gone. Connectomics and large-scale neuroinformatics initiatives are emerging everywhere. So where is the dysconnection hypothesis now? This article considers how the notion of schizophrenia as a dysconnection syndrome has developed - and how it has been enriched by recent advances in clinical neuroscience. In particular, we examine the dysconnection hypothesis in the context of (i) theoretical neurobiology and computational psychiatry; (ii) the empirical insights afforded by neuroimaging and associated connectomics - and (iii) how bottom-up (molecular biology and genetics) and top-down (systems biology) perspectives are converging on the mechanisms and nature of dysconnections in schizophrenia.
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Affiliation(s)
- Karl Friston
- Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK.
| | - Harriet R. Brown
- Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, UK,Oxford Centre for Human Brain Activity, University of Oxford, UK
| | - Jakob Siemerkus
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Switzerland,Department of Psychiatry, Psychotherapy and Psychosomatics, Zurich, Switzerland
| | - Klaas E. Stephan
- Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Switzerland
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26
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27
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Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis. Schizophr Res 2016; 173:1-12. [PMID: 26965745 PMCID: PMC4836956 DOI: 10.1016/j.schres.2016.02.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 02/09/2016] [Accepted: 02/11/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Deficits in working memory (WM) are a core feature of schizophrenia (SZ) and other psychotic disorders. We examined brain activity during WM in persons at clinical high risk (CHR) for psychosis. METHODS Thirty-seven CHR and 34 healthy control participants underwent functional MRI (fMRI) on a 3.0T scanner while performing an N-back WM task. The sample included a sub-sample of CHR participants who had no lifetime history of treatment with psychotropic medications (n=11). Data were analyzed using SPM8 (2-back>0-back contrast). Pearson correlations between brain activity, symptoms, and WM performance were examined. RESULTS The total CHR group and medication-naive CHR sub-sample were comparable to controls in most demographic features and in N-back WM performance, but had significantly lower IQ. Relative to controls, medication-naïve CHR showed hyperactivity in the left parahippocampus (PHP) and the left caudate during performance of the N-back WM task. Relative to medication-exposed CHR, medication naïve CHR exhibited hyperactivity in the left caudate and the right dorsolateral prefrontal cortex (DLPFC). DLPFC activity was significantly negatively correlated with WM performance. PHP, caudate and DLPFC activity correlated strongly with symptoms, but results did not withstand FDR-correction for multiple comparisons. When all CHR participants were combined (regardless of medication status), only trend-level PHP hyperactivity was observed in CHR relative to controls. CONCLUSIONS Medication-naïve CHR exhibit hyperactivity in regions that subserve WM. These regions are implicated in studies of schizophrenia and risk for psychosis. Results emphasize the importance of medication status in the interpretation of task - induced brain activity.
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28
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Zheng Y, Wu C, Li J, Wu H, She S, Liu S, Mao L, Ning Y, Li L. Brain substrates of perceived spatial separation between speech sources under simulated reverberant listening conditions in schizophrenia. Psychol Med 2016; 46:477-491. [PMID: 26423774 DOI: 10.1017/s0033291715001828] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND People with schizophrenia recognize speech poorly under multiple-people-talking (informational masking) conditions. In reverberant environments, direct-wave signals from a speech source are perceptually integrated with the source reflections (the precedence effect), forming perceived spatial separation (PSS) between different sources and consequently improving target-speech recognition against informational masking. However, the brain substrates underlying the schizophrenia-related vulnerability to informational masking and whether schizophrenia affects the unmasking effect of PSS are largely unknown. METHOD Using psychoacoustic testing and functional magnetic resonance imaging, respectively, the speech recognition under either the PSS or perceived spatial co-location (PSC) condition and the underlying brain substrates were examined in 20 patients with schizophrenia and 16 healthy controls. RESULTS Speech recognition was worse in patients than controls. Under the PSS (but not PSC) condition, speech recognition was correlated with activation of the superior parietal lobule (SPL), and target speech-induced activation of the SPL, precuneus, middle cingulate cortex and caudate significantly declined in patients. Moreover, the separation (PSS)-against-co-location (PSC) contrast revealed (1) activation of the SPL, precuneus and anterior cingulate cortex in controls, (2) suppression of the SPL and precuneus in patients, (3) activation of the pars triangularis of the inferior frontal gyrus and middle frontal gyrus in both controls and patients, (4) activation of the medial superior frontal gyrus in patients, and (5) impaired functional connectivity of the SPL in patients. CONCLUSIONS Introducing the PSS listening condition efficiently reveals both the brain substrates underlying schizophrenia-related speech-recognition deficits against informational masking and the schizophrenia-related neural compensatory strategy for impaired SPL functions.
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Affiliation(s)
- Y Zheng
- Guangzhou Brain Hospital, the Affiliated Hospital of Guangzhou Medical University,Guangzhou 510370,People's Republic of China
| | - C Wu
- Department of Psychology,School of Life Sciences,McGovern Institute for Brain Research at PKU,Key Laboratory on Machine Perception (Ministry of Education),Peking University,Beijing 100871,People's Republic of China
| | - J Li
- Guangzhou Brain Hospital, the Affiliated Hospital of Guangzhou Medical University,Guangzhou 510370,People's Republic of China
| | - H Wu
- Guangzhou Brain Hospital, the Affiliated Hospital of Guangzhou Medical University,Guangzhou 510370,People's Republic of China
| | - S She
- Guangzhou Brain Hospital, the Affiliated Hospital of Guangzhou Medical University,Guangzhou 510370,People's Republic of China
| | - S Liu
- Guangzhou Brain Hospital, the Affiliated Hospital of Guangzhou Medical University,Guangzhou 510370,People's Republic of China
| | - L Mao
- Department of Psychology,School of Life Sciences,McGovern Institute for Brain Research at PKU,Key Laboratory on Machine Perception (Ministry of Education),Peking University,Beijing 100871,People's Republic of China
| | - Y Ning
- Guangzhou Brain Hospital, the Affiliated Hospital of Guangzhou Medical University,Guangzhou 510370,People's Republic of China
| | - L Li
- Department of Psychology,School of Life Sciences,McGovern Institute for Brain Research at PKU,Key Laboratory on Machine Perception (Ministry of Education),Peking University,Beijing 100871,People's Republic of China
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29
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Ranlund S, Adams RA, Díez Á, Constante M, Dutt A, Hall MH, Maestro Carbayo A, McDonald C, Petrella S, Schulze K, Shaikh M, Walshe M, Friston K, Pinotsis D, Bramon E. Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity. Hum Brain Mapp 2015; 37:351-65. [PMID: 26503033 PMCID: PMC4843949 DOI: 10.1002/hbm.23035] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 09/30/2015] [Accepted: 10/13/2015] [Indexed: 12/11/2022] Open
Abstract
The mismatch negativity (MMN) evoked potential, a preattentive brain response to a discriminable change in auditory stimulation, is significantly reduced in psychosis. Glutamatergic theories of psychosis propose that hypofunction of NMDA receptors (on pyramidal cells and inhibitory interneurons) causes a loss of synaptic gain control. We measured changes in neuronal effective connectivity underlying the MMN using dynamic causal modeling (DCM), where the gain (excitability) of superficial pyramidal cells is explicitly parameterised. EEG data were obtained during a MMN task—for 24 patients with psychosis, 25 of their first‐degree unaffected relatives, and 35 controls—and DCM was used to estimate the excitability (modeled as self‐inhibition) of (source‐specific) superficial pyramidal populations. The MMN sources, based on previous research, included primary and secondary auditory cortices, and the right inferior frontal gyrus. Both patients with psychosis and unaffected relatives (to a lesser degree) showed increased excitability in right inferior frontal gyrus across task conditions, compared to controls. Furthermore, in the same region, both patients and their relatives showed a reversal of the normal response to deviant stimuli; that is, a decrease in excitability in comparison to standard conditions. Our results suggest that psychosis and genetic risk for the illness are associated with both context‐dependent (condition‐specific) and context‐independent abnormalities of the excitability of superficial pyramidal cell populations in the MMN paradigm. These abnormalities could relate to NMDA receptor hypofunction on both pyramidal cells and inhibitory interneurons, and appear to be linked to the genetic aetiology of the illness, thereby constituting potential endophenotypes for psychosis. Hum Brain Mapp 37:351–365, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
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Affiliation(s)
- Siri Ranlund
- Division of Psychiatry, University College London, London, United Kingdom
| | - Rick A Adams
- Division of Psychiatry, University College London, London, United Kingdom.,Institute of Cognitive Neuroscience, University College London, London, United Kingdom
| | - Álvaro Díez
- Division of Psychiatry, University College London, London, United Kingdom
| | - Miguel Constante
- Department of Psychiatry, Hospital Beatriz Angelo, Lisbon, Portugal
| | - Anirban Dutt
- The South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - Mei-Hua Hall
- Psychology Research Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA
| | - Amparo Maestro Carbayo
- The South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - Colm McDonald
- Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland
| | - Sabrina Petrella
- The South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.,Department of Psychiatry, Clinical and Experimental Science Institute, University of Foggia, Italy
| | - Katja Schulze
- The South London and Maudsley NHS Foundation Trust, University Hospital Lewisham, London, United Kingdom
| | - Madiha Shaikh
- The South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.,Neuroepidemiology and Ageing Research Unit, Imperial College, London, United Kingdom
| | - Muriel Walshe
- Division of Psychiatry, University College London, London, United Kingdom.,The South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - Karl Friston
- The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom
| | - Dimitris Pinotsis
- The Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom
| | - Elvira Bramon
- Division of Psychiatry, University College London, London, United Kingdom.,Institute of Cognitive Neuroscience, University College London, London, United Kingdom.,The South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
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30
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Bendfeldt K, Smieskova R, Koutsouleris N, Klöppel S, Schmidt A, Walter A, Harrisberger F, Wrege J, Simon A, Taschler B, Nichols T, Riecher-Rössler A, Lang UE, Radue EW, Borgwardt S. Classifying individuals at high-risk for psychosis based on functional brain activity during working memory processing. NEUROIMAGE-CLINICAL 2015; 9:555-63. [PMID: 26640767 PMCID: PMC4625212 DOI: 10.1016/j.nicl.2015.09.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Revised: 09/22/2015] [Accepted: 09/23/2015] [Indexed: 11/04/2022]
Abstract
The psychosis high-risk state is accompanied by alterations in functional brain activity during working memory processing. We used binary automatic pattern-classification to discriminate between the at-risk mental state (ARMS), first episode psychosis (FEP) and healthy controls (HCs) based on n-back WM-induced brain activity. Linear support vector machines and leave-one-out-cross-validation were applied to fMRI data of matched ARMS, FEP and HC (19 subjects/group). The HC and ARMS were correctly classified, with an accuracy of 76.2% (sensitivity 89.5%, specificity 63.2%, p = 0.01) using a verbal working memory network mask. Only 50% and 47.4% of individuals were classified correctly for HC vs. FEP (p = 0.46) or ARMS vs. FEP (p = 0.62), respectively. Without mask, accuracy was 65.8% for HC vs. ARMS (p = 0.03) and 65.8% for HC vs. FEP (p = 0.0047), and 57.9% for ARMS vs. FEP (p = 0.18). Regions in the medial frontal, paracingulate, cingulate, inferior frontal and superior frontal gyri, inferior and superior parietal lobules, and precuneus were particularly important for group separation. These results suggest that FEP and HC or FEP and ARMS cannot be accurately separated in small samples under these conditions. However, ARMS can be identified with very high sensitivity in comparison to HC. This might aid classification and help to predict transition in the ARMS.
The ARMS was accurately identified based on an individual patient's response within a WM network. Regional cortical activations were particularly important for group separation. Based on WM alterations, FEP and HC or FEP and ARMS could not be accurately separated in small samples.
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Affiliation(s)
- Kerstin Bendfeldt
- Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland
| | - Renata Smieskova
- Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Nikolaos Koutsouleris
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Nussbaumstr. 7, Munich 80336, Germany
| | - Stefan Klöppel
- Department of Psychiatry and Psychotherapy, University Medical Center, Freiburg, Freiburg, Germany
| | - André Schmidt
- Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Anna Walter
- Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Fabienne Harrisberger
- Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Johannes Wrege
- Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Andor Simon
- University Hospital of Psychiatry, University of Bern, Bern 3010, Switzerland
| | - Bernd Taschler
- Dept. of Statistics, University of Warwick, Coventry, UK
| | - Thomas Nichols
- Dept. of Statistics, University of Warwick, Coventry, UK
| | - Anita Riecher-Rössler
- Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Undine E Lang
- Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland
| | - Ernst-Wilhelm Radue
- Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland
| | - Stefan Borgwardt
- Medical Image Analysis Centre, University Hospital Basel, Mittlere Strasse 83, Basel 4031, Switzerland ; Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse, 27, Basel 4056, Switzerland ; Department of Psychosis Studies, King's College London, Institute of Psychiatry, De Crespigny Park 16, London SE58AF, UK
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31
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Fonville L, Cohen Kadosh K, Drakesmith M, Dutt A, Zammit S, Mollon J, Reichenberg A, Lewis G, Jones DK, David AS. Psychotic Experiences, Working Memory, and the Developing Brain: A Multimodal Neuroimaging Study. Cereb Cortex 2015; 25:4828-38. [PMID: 26286920 PMCID: PMC4635922 DOI: 10.1093/cercor/bhv181] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs.
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Affiliation(s)
- Leon Fonville
- Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | | | - Mark Drakesmith
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology Institute of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK
| | - Anirban Dutt
- Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Stanley Zammit
- Institute of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Josephine Mollon
- Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Abraham Reichenberg
- Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK Department of Psychiatry, Icahn School of Medicine, Mount Sinai Hospital, New York, NY, USA
| | - Glyn Lewis
- Division of Psychiatry, Faculty of Brain Sciences, University College London, London, UK
| | - Derek K Jones
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology Institute of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK
| | - Anthony S David
- Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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32
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Rausch F, Mier D, Eifler S, Fenske S, Schirmbeck F, Englisch S, Schilling C, Meyer-Lindenberg A, Kirsch P, Zink M. Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state. J Psychiatry Neurosci 2015; 40:163-73. [PMID: 25622039 PMCID: PMC4409434 DOI: 10.1503/jpn.140191] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS). METHODS We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making. RESULTS We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage. LIMITATIONS Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not prepsychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam. CONCLUSION As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk.
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Affiliation(s)
- Franziska Rausch
- Correspondence to: F. Rausch, Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim/Heidelberg University J5D-68159, Mannheim, Germany;
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33
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Abstract
PURPOSE OF REVIEW The neural connections, interconnections and organized networks of the central nervous system (CNS), which represent the human connectome, are critical for intact brain function. Consequently, disturbances at any level or juncture of these networks may alter behaviour and/or lead to brain dysfunction. In this review, we focus on highlighting recent work using advanced imaging methods to address alterations in the structural and functional connectome in patients with schizophrenia. RECENT FINDINGS Using structural, diffusion, resting-state and task-related functional imaging and advanced computational analysis methods such as graph theory, more than 200 publications have addressed different aspects of structural and/or functional connectivity in schizophrenia over the last year. These studies have focused on determining how brain networks differ from those in controls, interact with symptom profiles within and across diagnoses, interface with disease-related cognitive impairments and confer genetic risk for the disorder. SUMMARY Much existing evidence supports the view that schizophrenia is a disorder of altered brain connectivity. Recent and continued characterization of the structural and functional connectome in schizophrenia patients have advanced our understanding of the neurobiology underlying clinical symptoms and cognitive impairments in a particular patient, their overlaps with other neuropsychiatric disorders sharing common features as well as the contributions of genetic risk factors. Although the clinical utility of the schizophrenia connectome remains to be realized, recent findings provide further promise that research in this area may lead to improved diagnosis, treatments and clinical outcomes.
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34
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Dawson N, Morris BJ, Pratt JA. Functional brain connectivity phenotypes for schizophrenia drug discovery. J Psychopharmacol 2015; 29:169-77. [PMID: 25567554 DOI: 10.1177/0269881114563635] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
While our knowledge of the pathophysiology of schizophrenia has increased dramatically, this has not translated into the development of new and improved drugs to treat this disorder. Human brain imaging and electrophysiological studies have provided dramatic new insight into the mechanisms of brain dysfunction in the disease, with a swathe of recent studies highlighting the differences in functional brain network and neural system connectivity present in the disorder. Only recently has the value of applying these approaches in preclinical rodent models relevant to the disorder started to be recognised. Here we highlight recent findings of altered functional brain connectivity in preclinical rodent models and consider their relevance to those alterations seen in the brains of schizophrenia patients. Furthermore, we highlight the potential translational value of using the paradigm of functional brain connectivity phenotypes in the context of preclinical schizophrenia drug discovery, as a means both to understand the mechanisms of brain dysfunction in the disorder and to reduce the current high attrition rate in schizophrenia drug discovery.
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Affiliation(s)
- Neil Dawson
- Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK
| | - Brian J Morris
- Institute of Neuroscience and Psychology, School of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK Psychiatric Research Institute of Neuroscience in Glasgow (PsyRING), University of Glasgow, Glasgow, UK
| | - Judith A Pratt
- Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow, UK Psychiatric Research Institute of Neuroscience in Glasgow (PsyRING), University of Glasgow, Glasgow, UK
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35
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Schmidt A, Diwadkar VA, Smieskova R, Harrisberger F, Lang UE, McGuire P, Fusar-Poli P, Borgwardt S. Approaching a network connectivity-driven classification of the psychosis continuum: a selective review and suggestions for future research. Front Hum Neurosci 2015; 8:1047. [PMID: 25628553 PMCID: PMC4292722 DOI: 10.3389/fnhum.2014.01047] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 12/15/2014] [Indexed: 01/07/2023] Open
Abstract
Brain changes in schizophrenia evolve along a dynamic trajectory, emerging before disease onset and proceeding with ongoing illness. Recent investigations have focused attention on functional brain interactions, with experimental imaging studies supporting the disconnection hypothesis of schizophrenia. These studies have revealed a broad spectrum of abnormalities in brain connectivity in patients, particularly for connections integrating the frontal cortex. A critical point is that brain connectivity abnormalities, including altered resting state connectivity within the fronto-parietal (FP) network, are already observed in non-help-seeking individuals with psychotic-like experiences. If we consider psychosis as a continuum, with individuals with psychotic-like experiences at the lower and psychotic patients at the upper ends, individuals with psychotic-like experiences represent a key population for investigating the validity of putative biomarkers underlying the onset of psychosis. This paper selectively addresses the role played by FP connectivity in the psychosis continuum, which includes patients with chronic psychosis, early psychosis, clinical high risk, genetic high risk, as well as the general population with psychotic experiences. We first discuss structural connectivity changes among the FP pathway in each domain in the psychosis continuum. This may provide a basis for us to gain an understanding of the subsequent changes in functional FP connectivity. We further indicate that abnormal FP connectivity may arise from glutamatergic disturbances of this pathway, in particular from abnormal NMDA receptor-mediated plasticity. In the second part of this paper we propose some concepts for further research on the use of network connectivity in the classification of the psychosis continuum. These concepts are consistent with recent efforts to enhance the role of data in driving the diagnosis of psychiatric spectrum diseases.
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Affiliation(s)
- André Schmidt
- Department of Psychiatry (UPK), University of Basel Basel, Switzerland
| | - Vaibhav A Diwadkar
- Department of Psychiatry and Behavioral Neurosciences, Wayne State University Detroit, Michigan, USA
| | - Renata Smieskova
- Department of Psychiatry (UPK), University of Basel Basel, Switzerland
| | | | - Undine E Lang
- Department of Psychiatry (UPK), University of Basel Basel, Switzerland
| | - Philip McGuire
- Department of Psychosis Studies, Institute of Psychiatry, King's College London London, UK
| | - Paolo Fusar-Poli
- Department of Psychosis Studies, Institute of Psychiatry, King's College London London, UK
| | - Stefan Borgwardt
- Department of Psychiatry (UPK), University of Basel Basel, Switzerland ; Department of Psychosis Studies, Institute of Psychiatry, King's College London London, UK
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36
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Harding IH, Yücel M, Harrison BJ, Pantelis C, Breakspear M. Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory. Neuroimage 2014; 106:144-53. [PMID: 25463464 DOI: 10.1016/j.neuroimage.2014.11.039] [Citation(s) in RCA: 111] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 11/13/2014] [Accepted: 11/18/2014] [Indexed: 10/24/2022] Open
Abstract
Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control.
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Affiliation(s)
- Ian H Harding
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Melbourne, Australia; Monash Clinical and Imaging Neuroscience, School of Psychological Sciences, Monash University, Melbourne, Australia.
| | - Murat Yücel
- Monash Clinical and Imaging Neuroscience, School of Psychological Sciences, Monash University, Melbourne, Australia
| | - Ben J Harrison
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Melbourne, Australia
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne & Melbourne Health, Melbourne, Australia
| | - Michael Breakspear
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Metro North Mental Health Service, Brisbane, QLD, Australia
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