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Torres FA, Otero M, Lea-Carnall CA, Cabral J, Weinstein A, El-Deredy W. Emergence of multiple spontaneous coherent subnetworks from a single configuration of human connectome coupled oscillators model. Sci Rep 2024; 14:30726. [PMID: 39730441 DOI: 10.1038/s41598-024-80510-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 11/19/2024] [Indexed: 12/29/2024] Open
Abstract
Multi-state metastability in neuroimaging signals reflects the brain's flexibility to transition between network configurations in response to changing environments or tasks. We modeled these dynamics with a Kuramoto network of 90 nodes oscillating at an intrinsic frequency of 40 Hz, interconnected using human brain structural connectivity strengths and delays. We simulated this model for 30 min to generate multi-state metastability. We identified global coupling and delay parameters that maximize spectral entropy, a proxy for multi-state metastability. At this operational point, multiple frequency-specific coherent sub-networks spontaneously emerge across oscillatory modes, persisting for periods between 140 and 4300 ms, reflecting flexible and sustained dynamic states. The topography of these sub-networks aligns with empirical resting-state neuroimaging data. Additionally, periodic components of the EEG spectra from young healthy participants correlate with maximal multi-state metastability, while dynamics away from this point correlate with sleep and anesthesia spectra. Our findings suggest that multi-state metastable functional dynamics observed in empirical data emerge from specific interactions of structural topography and connection delays, providing a platform to study mechanisms underlying flexible dynamics of cognition.
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Affiliation(s)
- Felipe A Torres
- Departamento de Computación e Industrias, Facultad de Ciencias de la Ingeniería, Universidad Católica del Maule, Talca, Chile
| | - Mónica Otero
- Facultad de Ingeniería, Arquitectura y Diseño, Universidad San Sebastián, Santiago, Chile
- Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Universidad San Sebastián, Santiago, Chile
| | - Caroline A Lea-Carnall
- School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Manchester, UK
| | - Joana Cabral
- Life and Health Sciences Research Institute, Minho University, Braga, Portugal
| | - Alejandro Weinstein
- Department of Electronic Engineering, Universidad Técnica Federico Santa María, Valparaíso, Chile
| | - Wael El-Deredy
- Brain Dynamics Lab, Interdisciplinary Center of Biomedical and Engineering Research for Health, Universidad de Valparaíso, Valparaíso, Chile.
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2
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Weerasekera A, Ion-Mărgineanu A, Nolan GP, Mody M. Subcortical-cortical white matter connectivity in adults with autism spectrum disorder and schizophrenia patients. Psychiatry Res Neuroimaging 2024; 340:111806. [PMID: 38508025 DOI: 10.1016/j.pscychresns.2024.111806] [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: 09/01/2023] [Revised: 11/20/2023] [Accepted: 02/29/2024] [Indexed: 03/22/2024]
Abstract
Autism spectrum disorder (ASD) and schizophrenia (SZ) are neuropsychiatric disorders that overlap in symptoms associated with social-cognitive impairment. Alterations of the cingulate cortex, subcortical, medial-temporal, and orbitofrontal structures are frequently reported in both disorders. In this study, we examined white-matter connectivity between these structures in adults with ASD and SZ patients compared with their respective neurotypical controls and indirectly with each other, using probabilistic and local DTI tractography. This exploratory study utilized publicly available neuroimaging databases, of adults with ASD (ABIDE II; n = 28) and SZ (COBRE; n = 38), age-gender matched neurotypicals (NT) and associated phenotypic data. Tractography was performed using Freesurfer and MRtrix software, and diffusion metrics of white-matter tracts between cingulate-, orbitofrontal- cortices, subcortical structures, parahippocampal, entorhinal cortex were assessed. In ASD, atypical diffusivity parameters were found in the isthmus cingulate and parahippocampal connectivity to subcortical and rostral-anterior cingulate, which were also associated with IQ and social skills (SRS). In contrast, atypical diffusivity parameters were observed between the medial-orbitofrontal cortex and subcortical structures in SZ, and were associated with executive function (i.e., IQ, processing speed) and emotional regulation. Overall, the results suggest that defects in the isthmus cingulate, medial-orbitofrontal, and striato-limbic white matter connectivity may help unravel the neural underpinnings of executive and social-emotional dysfunction at the core of neuropsychiatric disorders.
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Affiliation(s)
- Akila Weerasekera
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.
| | - Adrian Ion-Mărgineanu
- ESAT - STADIUS, KU Leuven, Leuven. Belgium; Biomed Artificial Intelligence LLC, Bucharest, Romania
| | - Garry P Nolan
- Department of Microbiology & Immunology, Stanford University School of Medicine, United States
| | - Maria Mody
- Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA
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3
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Gaus R, Popal M, Heinsen H, Schmitt A, Falkai P, Hof PR, Schmitz C, Vollhardt A. Reduced cortical neuron number and neuron density in schizophrenia with focus on area 24: a post-mortem case-control study. Eur Arch Psychiatry Clin Neurosci 2023; 273:1209-1223. [PMID: 36350376 PMCID: PMC10449727 DOI: 10.1007/s00406-022-01513-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 10/26/2022] [Indexed: 11/10/2022]
Abstract
Structural and functional abnormalities of the anterior cingulate cortex (ACC) have frequently been identified in schizophrenia. Alterations of von Economo neurons (VENs), a class of specialized projection neurons, have been found in different neuropsychiatric disorders and are also suspected in schizophrenia. To date, however, no definitive conclusions can be drawn about quantitative histologic changes in the ACC in schizophrenia because of a lack of rigorous, design-based stereologic studies. In the present study, the volume, total neuron number and total number of VENs in layer V of area 24 were determined in both hemispheres of postmortem brains from 12 male patients with schizophrenia and 11 age-matched male controls. To distinguish global from local effects, volume and total neuron number were also determined in the whole area 24 and whole cortical gray matter (CGM). Measurements were adjusted for hemisphere, age, postmortem interval and fixation time using an ANCOVA model. Compared to controls, patients with schizophrenia showed alterations, with lower mean total neuron number in CGM (- 14.9%, P = 0.007) and in layer V of area 24 (- 21.1%, P = 0.002), and lower mean total number of VENs (- 28.3%, P = 0.027). These data provide evidence for ACC involvement in the pathophysiology of schizophrenia, and complement neuroimaging findings of impaired ACC connectivity in schizophrenia. Furthermore, these results support the hypothesis that the clinical presentation of schizophrenia, particularly deficits in social cognition, is associated with pathology of VENs.
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Affiliation(s)
- Richard Gaus
- Department of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
| | - Melanie Popal
- Department of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
| | - Helmut Heinsen
- Morphological Brain Research Unit, Department of Psychiatry, University of Würzburg, Würzburg, Germany
| | - Andrea Schmitt
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
- Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil
| | - Peter Falkai
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Patrick R. Hof
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA
| | - Christoph Schmitz
- Department of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
| | - Alisa Vollhardt
- Department of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, 80336 Munich, Germany
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4
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Dimitriadis SI, Perry G, Lancaster TM, Tansey KE, Singh KD, Holmans P, Pocklington A, Davey Smith G, Zammit S, Hall J, O’Donovan MC, Owen MJ, Jones DK, Linden DE. Genetic risk for schizophrenia is associated with increased proportion of indirect connections in brain networks revealed by a semi-metric analysis: evidence from population sample stratified for polygenic risk. Cereb Cortex 2023; 33:2997-3011. [PMID: 35830871 PMCID: PMC10016061 DOI: 10.1093/cercor/bhac256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 02/02/2023] Open
Abstract
Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR < 0.05). These findings might indicate less efficient structural connectivity in the higher genetic risk group. This is the first study in a population-based sample that reveals differences in the efficiency of SBNs associated with common genetic risk variants for SCZ.
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Affiliation(s)
- S I Dimitriadis
- Neuroscience and Mental Health Research Institute (NMHI), College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Neuroinformatics Group, School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - G Perry
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - T M Lancaster
- Neuroscience and Mental Health Research Institute (NMHI), College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Department of Psychology, Bath University, Claverton Down BA2 7AY, Bath, Wales, UK
| | - K E Tansey
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Queens Road BS8 1QU, Bristol, Wales, UK
| | - K D Singh
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - P Holmans
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - A Pocklington
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - G Davey Smith
- MRC Integrative Epidemiology Unit (IEU), University of Bristol, Queens Road BS8 1QU, Bristol, Wales, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, 1-5 Whiteladies Road BS8 1NU, Bristol, Wales, UK
| | - S Zammit
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, 1-5 Whiteladies Road BS8 1NU, Bristol, Wales, UK
| | - J Hall
- Neuroscience and Mental Health Research Institute (NMHI), College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - M C O’Donovan
- Neuroscience and Mental Health Research Institute (NMHI), College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - M J Owen
- Neuroscience and Mental Health Research Institute (NMHI), College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - D K Jones
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
| | - D E Linden
- Neuroscience and Mental Health Research Institute (NMHI), College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, College of Biomedical and Life Sciences, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff School of Medicine, Cardiff University, Maindy Road CF24 4HQ, Cardiff, Wales, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, 1-5 Whiteladies Road BS8 1NU, Bristol, Wales, UK
- School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 40 UNS40 6229 ER, Maastricht, The Netherlands
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Roddy DW, Roman E, Nasa A, Gazzaz A, Zainy A, Burke T, Staines L, Kelleher I, O'Neill A, Clarke M, O'Hanlon E, Cannon M. Microstructural changes along the cingulum in young adolescents with psychotic experiences: An along-tract analysis. Eur J Neurosci 2022; 56:5116-5131. [PMID: 36004608 PMCID: PMC9825926 DOI: 10.1111/ejn.15806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 07/30/2022] [Accepted: 08/18/2022] [Indexed: 01/11/2023]
Abstract
Psychotic experiences (PEs) such as hallucinations and delusions are common among young people without psychiatric diagnoses and are associated with connectivity and white matter abnormalities, particularly in the limbic system. Using diffusion magnetic resonance imaging (MRI) in adolescents with reported PEs and matched controls, we examined the cingulum white matter tract along its length rather than as the usually reported single indivisible structure. Complex regional differences in diffusion metrics were found along the bundle at key loci following Bonferroni significance adjustment (p < .00013) with moderate to large effect sizes (.11-.76) throughout all significant subsegments. In this prospective community-based cohort of school-age children, these findings suggest that white matter alterations in the limbic system may be more common in the general non-clinical adolescent population than previously thought. Such white matter alternations may only be uncovered using a similar more granular along-tract analysis of white matter tracts.
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Affiliation(s)
- Darren William Roddy
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland,Trinity College Institute of Neuroscience, Lloyd BuildingTrinity College DublinDublinIreland
| | - Elena Roman
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Anurag Nasa
- Trinity College Institute of Neuroscience, Lloyd BuildingTrinity College DublinDublinIreland
| | - Areej Gazzaz
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Ahmed Zainy
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Tom Burke
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Lorna Staines
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Ian Kelleher
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Aisling O'Neill
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Mary Clarke
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
| | - Erik O'Hanlon
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland,Trinity College Institute of Neuroscience, Lloyd BuildingTrinity College DublinDublinIreland
| | - Mary Cannon
- Department of PsychiatryRoyal College of Surgeons in IrelandDublinIreland
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Valdés-Tovar M, Rodríguez-Ramírez AM, Rodríguez-Cárdenas L, Sotelo-Ramírez CE, Camarena B, Sanabrais-Jiménez MA, Solís-Chagoyán H, Argueta J, López-Riquelme GO. Insights into myelin dysfunction in schizophrenia and bipolar disorder. World J Psychiatry 2022; 12:264-285. [PMID: 35317338 PMCID: PMC8900585 DOI: 10.5498/wjp.v12.i2.264] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/10/2021] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both disorders present chronic and deteriorating prognoses that impose a large burden, not only on patients but also on society and health systems. These mental illnesses share several clinical and neurobiological traits; of these traits, oligodendroglial dysfunction and alterations to white matter (WM) tracts could underlie the disconnection between brain regions related to their symptomatic domains. WM is mainly composed of heavily myelinated axons and glial cells. Myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. Myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier, improving the overall function of neuronal circuits. Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions, such as cognition, memory, mood, and language. Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder, and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders. In this work, evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed, and the involvement of proteins in key functions of the oligodendroglial lineage, such as oligodendrogenesis and myelination, is highlighted. The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.
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Affiliation(s)
- Marcela Valdés-Tovar
- Departamento de Farmacogenética, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | | | - Leslye Rodríguez-Cárdenas
- Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | - Carlo E Sotelo-Ramírez
- Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
- Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico
| | - Beatriz Camarena
- Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | | | - Héctor Solís-Chagoyán
- Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | - Jesús Argueta
- Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico
- Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | - Germán Octavio López-Riquelme
- Laboratorio de Socioneurobiología, Centro de Investigación en Ciencias Cognitivas, Universidad del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
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7
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Pan Y, Dempster K, Jeon P, Théberge J, Khan AR, Palaniyappan L. Acute conceptual disorganization in untreated first-episode psychosis: a combined magnetic resonance spectroscopy and diffusion imaging study of the cingulum. J Psychiatry Neurosci 2021; 46:E337-E346. [PMID: 33904669 PMCID: PMC8327974 DOI: 10.1503/jpn.200167] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Disorganized thinking is a core feature of acute psychotic episodes that is linked to social and vocational functioning. Several lines of evidence implicate disrupted cognitive control, excitatory overdrive and oxidative stress relating to the anterior cingulate cortex as mechanisms of conceptual disorganization (CD). We examined 3 candidate mechanistic markers related to CD in firstepisode psychosis: glutamate excess, cortical antioxidant (glutathione) status and the integrity of the cingulum bundle that connects regions implicated in cognitive control. METHODS We used fractional anisotropy maps from 7 T diffusion-weighted imaging to investigate the bilateral cingulum based on a probabilistic white matter atlas. We compared high CD, low CD and healthy control groups and performed probabilistic fibre tracking from the identified clusters (regions of interest within the cingulum) to the rest of the brain. We quantified glutamate and glutathione using magnetic resonance spectroscopy (MRS) in the dorsal anterior cingulate cortex. RESULTS We found a significant fractional anisotropy reduction in a cluster in the left cingulum in the high CD group compared to the low CD group (Cohen's d = 1.39; p < 0.001) and controls (Cohen's d = 0.86; p = 0.009). Glutamate levels did not vary among groups, but glutathione levels were higher in the high CD group than in the low CD group. We also found higher glutathione related to lower fractional anisotropy in the cingulum cluster in the high CD group. LIMITATIONS The MRS measures of glutamine were highly uncertain, and MRS was acquired from a single voxel only. CONCLUSION Acute CD relates to indicators of oxidative stress, as well as reduced white matter integrity of the cingulum, but not to MRI-based glutamatergic excess. We propose that both oxidative imbalance and structural dysconnectivity underlie acute disorganization.
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Affiliation(s)
- Yunzhi Pan
- From the Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Pan); the Robarts Research Institute, University of Western Ontario, London, Ont., Canada (Pan, Khan, Palaniyappan); the Lawson Health Research Institute, London, Ont., Canada (Théberge, Palaniyappan); the Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada (Jeon, Théberge, Khan, Palaniyappan); the Department of Psychiatry, University of Western Ontario, London, Ont., Canada (Palaniyappan, Théberge); the Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Dempster); the China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China (Pan); the China National Technology Institute on Mental Disorders, Changsha, Hunan, China (Pan); the Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China (Pan); and the Institute of Mental Health of Second Xiangya Hospital, Central South University, Changsha, Hunan, China (Pan)
| | - Kara Dempster
- From the Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Pan); the Robarts Research Institute, University of Western Ontario, London, Ont., Canada (Pan, Khan, Palaniyappan); the Lawson Health Research Institute, London, Ont., Canada (Théberge, Palaniyappan); the Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada (Jeon, Théberge, Khan, Palaniyappan); the Department of Psychiatry, University of Western Ontario, London, Ont., Canada (Palaniyappan, Théberge); the Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Dempster); the China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China (Pan); the China National Technology Institute on Mental Disorders, Changsha, Hunan, China (Pan); the Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China (Pan); and the Institute of Mental Health of Second Xiangya Hospital, Central South University, Changsha, Hunan, China (Pan)
| | - Peter Jeon
- From the Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Pan); the Robarts Research Institute, University of Western Ontario, London, Ont., Canada (Pan, Khan, Palaniyappan); the Lawson Health Research Institute, London, Ont., Canada (Théberge, Palaniyappan); the Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada (Jeon, Théberge, Khan, Palaniyappan); the Department of Psychiatry, University of Western Ontario, London, Ont., Canada (Palaniyappan, Théberge); the Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Dempster); the China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China (Pan); the China National Technology Institute on Mental Disorders, Changsha, Hunan, China (Pan); the Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China (Pan); and the Institute of Mental Health of Second Xiangya Hospital, Central South University, Changsha, Hunan, China (Pan)
| | - Jean Théberge
- From the Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Pan); the Robarts Research Institute, University of Western Ontario, London, Ont., Canada (Pan, Khan, Palaniyappan); the Lawson Health Research Institute, London, Ont., Canada (Théberge, Palaniyappan); the Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada (Jeon, Théberge, Khan, Palaniyappan); the Department of Psychiatry, University of Western Ontario, London, Ont., Canada (Palaniyappan, Théberge); the Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Dempster); the China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China (Pan); the China National Technology Institute on Mental Disorders, Changsha, Hunan, China (Pan); the Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China (Pan); and the Institute of Mental Health of Second Xiangya Hospital, Central South University, Changsha, Hunan, China (Pan)
| | - Ali R Khan
- From the Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Pan); the Robarts Research Institute, University of Western Ontario, London, Ont., Canada (Pan, Khan, Palaniyappan); the Lawson Health Research Institute, London, Ont., Canada (Théberge, Palaniyappan); the Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada (Jeon, Théberge, Khan, Palaniyappan); the Department of Psychiatry, University of Western Ontario, London, Ont., Canada (Palaniyappan, Théberge); the Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Dempster); the China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China (Pan); the China National Technology Institute on Mental Disorders, Changsha, Hunan, China (Pan); the Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China (Pan); and the Institute of Mental Health of Second Xiangya Hospital, Central South University, Changsha, Hunan, China (Pan)
| | - Lena Palaniyappan
- From the Department of Psychiatry, Second Xiangya Hospital of Central South University, Changsha, Hunan, China (Pan); the Robarts Research Institute, University of Western Ontario, London, Ont., Canada (Pan, Khan, Palaniyappan); the Lawson Health Research Institute, London, Ont., Canada (Théberge, Palaniyappan); the Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada (Jeon, Théberge, Khan, Palaniyappan); the Department of Psychiatry, University of Western Ontario, London, Ont., Canada (Palaniyappan, Théberge); the Department of Psychiatry, Dalhousie University, Halifax, NS, Canada (Dempster); the China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China (Pan); the China National Technology Institute on Mental Disorders, Changsha, Hunan, China (Pan); the Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China (Pan); and the Institute of Mental Health of Second Xiangya Hospital, Central South University, Changsha, Hunan, China (Pan)
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Abnormal white matter functional connectivity density in antipsychotic-naive adolescents with schizophrenia. Clin Neurophysiol 2021; 132:1025-1032. [PMID: 33743297 DOI: 10.1016/j.clinph.2020.12.031] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 12/14/2020] [Accepted: 12/27/2020] [Indexed: 01/01/2023]
Abstract
OBJECTIVES This study aimed to assess the white matter (WM) functional hubs and abnormal functional connectivity pattern in adolescents with schizophrenia (AOS) and to explore the potential mechanisms. METHODS Based on resting-state fMRI data, we measured the WM functional connectivity density (FCD) at local- and long- ranges in 39 AOS and 31 healthy controls (HCs). Group comparison was conducted between the two groups. Spearman rank correlation analysis between the altered WM FCD and clinical PANSS scores was performed. RESULTS In the local scale, the functional hubs of the WM were mainly located in the corona radiata and cerebellum. Compared with HCs, AOS patients exhibited decreased FCD in the superior corona radiata. In the long-range, the functional hubs of the WM were mainly located in the external capsule and pons. AOS patients exhibited increased FCD in the cingulum but decreased FCD in the right dorsal raphe nuclei (DR). Furthermore, the aberrant long-range FCD in the right DR was inversely proportional to the clinical symptoms. CONCLUSION These findings indicated that the pathophysiology of schizophrenia may also lie in WM functional dysconnectivity. SIGNIFICANCE The current results provided initial evidence for the hypothesis of abnormal WM functional connectivity in schizophrenia.
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Kim NS, Lee TY, Hwang WJ, Kwak YB, Kim S, Moon SY, Lho SK, Oh S, Kwon JS. White Matter Correlates of Theory of Mind in Patients With First-Episode Psychosis. Front Psychiatry 2021; 12:617683. [PMID: 33746794 PMCID: PMC7973210 DOI: 10.3389/fpsyt.2021.617683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 02/08/2021] [Indexed: 11/15/2022] Open
Abstract
Deficits in theory of mind (ToM) are considered as a distinctive feature of schizophrenia. Functional magnetic resonance imaging (fMRI) studies have suggested that aberrant activity among the regions comprising the mentalizing network is related to observed ToM deficits. However, the white matter structures underlying the ToM functional network in schizophrenia remain unclear. To investigate the relationship between white matter integrity and ToM impairment, 35 patients with first-episode psychosis (FEP) and 29 matched healthy controls (HCs) underwent diffusion tensor imaging (DTI). Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) values of the two regions of interest (ROI)-the cingulum and superior longitudinal fasciculus (SLF)-were acquired, and correlational analysis with ToM task scores was performed. Among the patients with FEP, ToM strange story scores were positively correlated with the FA values of the left cingulum and left SLF. There was no significant correlation between FA and ToM task scores in HCs. These results suggest that the left cingulum and SLF constitute a possible neural basis for ToM deficits in schizophrenia. Our study is the first to demonstrate the white matter connectivity underlying the mentalizing network, as well as its relation to ToM ability in patients with FEP.
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Affiliation(s)
- Nahrie Suk Kim
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, South Korea
- Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Tae Young Lee
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
- Department of Psychiatry, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Wu Jeong Hwang
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, South Korea
| | - Yoo Bin Kwak
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, South Korea
| | - Seowoo Kim
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, South Korea
| | - Sun-Young Moon
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
| | - Silvia Kyungjin Lho
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
| | - Sanghoon Oh
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
| | - Jun Soo Kwon
- Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, South Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
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10
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Adamczyk P, Płonka O, Kruk D, Jáni M, Błądziński P, Kalisz A, Castelein S, Cechnicki A, Wyczesany M. On the relation of white matter brain abnormalities and the asociality symptoms in schizophrenia outpatients - a DTI study. Acta Neurobiol Exp (Wars) 2021; 81:80-95. [PMID: 33949167 DOI: 10.21307/ane-2021-009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 01/29/2021] [Indexed: 11/11/2022]
Abstract
Recent MRI studies have shown that abnormal functional connections in schizophrenia coexist with subtle changes in the structure of axons in the brain. However, there is a discrepancy in the literature concerning the relationship between white matter abnormalities and the occurrence of negative psychopathological symptoms. In the present study, we investigate the relationship between the altered white matter structure and specific psychopathology symptoms, i.e., subscales of Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptoms Scale (BNSS) in a sample of schizophrenia outpatients. For investigation on white matter abnormalities in schizophrenia, the diffusion tensor imaging analysis of between-group differences in main diffusion parameters by tract-based spatial statistics was conducted on schizophrenia outpatients and healthy controls. Hence, the correlation of PANSS and BNSS psychopathology subscales in the clinical group with fractional anisotropy was analyzed in the 17 selected cortical regions of interest. Presented between-group results revealed widespread loss of white matter integrity located across the brain in schizophrenia outpatients. Results on the white matter relationship with psychopathology revealed the negative correlation between fractional anisotropy in the left orbital prefrontal cortex, right Heschl's gyrus, bilateral precuneus and posterior cingulate cortex and the severity of asociality, as assessed with the BNSS. In conclusion, the presented study confirms the previous evidence on the widespread white matter abnormalities in schizophrenia outpatients and indicates the existence of the subtle but specific association between fractional anisotropy in the fronto-temporo-parietal regions with the asociality. Recent MRI studies have shown that abnormal functional connections in schizophrenia coexist with subtle changes in the structure of axons in the brain. However, there is a discrepancy in the literature concerning the relationship between white matter abnormalities and the occurrence of negative psychopathological symptoms. In the present study, we investigate the relationship between the altered white matter structure and specific psychopathology symptoms, i.e., subscales of Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptoms Scale (BNSS) in a sample of schizophrenia outpatients. For investigation on white matter abnormalities in schizophrenia, the diffusion tensor imaging analysis of between-group differences in main diffusion parameters by tract-based spatial statistics was conducted on schizophrenia outpatients and healthy controls. Hence, the correlation of PANSS and BNSS psychopathology subscales in the clinical group with fractional anisotropy was analyzed in the 17 selected cortical regions of interest. Presented between-group results revealed widespread loss of white matter integrity located across the brain in schizophrenia outpatients. Results on the white matter relationship with psychopathology revealed the negative correlation between fractional anisotropy in the left orbital prefrontal cortex, right Heschl’s gyrus, bilateral precuneus and posterior cingulate cortex and the severity of asociality, as assessed with the BNSS. In conclusion, the presented study confirms the previous evidence on the widespread white matter abnormalities in schizophrenia outpatients and indicates the existence of the subtle but specific association between fractional anisotropy in the fronto-temporo-parietal regions with the asociality.
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Affiliation(s)
| | - Olga Płonka
- Institute of Psychology , Jagiellonian University , Krakow , Poland
| | - Dawid Kruk
- Psychosis Research and Psychotherapy Unit , Association for the Development of Community Psychiatry and Care , Krakow , Poland ; Community Psychiatry and Psychosis Research Center , Chair of Psychiatry , Medical College , Jagiellonian University , Krakow , Poland
| | - Martin Jáni
- Institute of Psychology , Jagiellonian University , Krakow , Poland ; Department of Psychiatry , Faculty of Medicine , Masaryk University and University Hospital Brno , Brno , Czech Republic
| | - Piotr Błądziński
- Community Psychiatry and Psychosis Research Center , Chair of Psychiatry , Medical College , Jagiellonian University , Krakow , Poland
| | - Aneta Kalisz
- Community Psychiatry and Psychosis Research Center , Chair of Psychiatry , Medical College , Jagiellonian University , Krakow , Poland
| | - Stynke Castelein
- Lentis Research , Lentis Psychiatric Institute , Groningen , The Netherlands ; Faculty of Behavioural and Social Sciences , University of Groningen , Groningen , The Netherlands
| | - Andrzej Cechnicki
- Psychosis Research and Psychotherapy Unit , Association for the Development of Community Psychiatry and Care , Krakow , Poland ; Community Psychiatry and Psychosis Research Center , Chair of Psychiatry , Medical College , Jagiellonian University , Krakow , Poland
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11
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Saito J, Nemoto T, Katagiri N, Hori M, Tagata H, Funatogawa T, Yamaguchi T, Tsujino N, Mizuno M. Can reduced leftward asymmetry of white matter integrity be a marker of transition to psychosis in at-risk mental state? Asian J Psychiatr 2020; 54:102450. [PMID: 33271729 DOI: 10.1016/j.ajp.2020.102450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 10/08/2020] [Accepted: 10/11/2020] [Indexed: 12/12/2022]
Abstract
As a biomarker for the degree of psychosis development, the lateral asymmetry of white matter (WM) integrity in each area of the cerebrum has been investigated; as a result, a reduced leftward asymmetry of WM integrity has been reported in patients with schizophrenia. Although individuals with an at-risk mental state for psychosis (ARMS) who subsequently develop psychosis are believed to have poorer social functioning, only a few studies have actually examined the associations between WM abnormalities and social functioning. The aim of the present study was to clarify the possibly predictive association between a reduced asymmetry of WM integrity and impairments in social functioning in patients with ARMS. Thirty ARMS subjects underwent MRI scanning and were assessed using the Social Functioning Scale (SFS). We examined the fractional anisotropy (FA) values in the cingulum bundle (CB) and the uncinate fasciculus (UF) using a tract-specific analysis. Lateral asymmetry was assessed using the laterality index (LI). The LI of the FA value was positive (leftward) in the CB and negative (rightward) in the UF. Although the LI was not correlated with the Scale of Prodromal Symptoms (SOPS) score, the LI in the CB was positively correlated with the SFS score. In ARMS patients, the degree of reduced leftward asymmetry in the CB might affect deteriorations in social functioning and may be useful as a biomarker for predicting future outcomes at an early stage of psychosis.
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Affiliation(s)
- Junichi Saito
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan; Department of Psychiatry, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan
| | - Takahiro Nemoto
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan.
| | - Naoyuki Katagiri
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan
| | - Masaaki Hori
- Department of Radiology, Toho University Omori Medical Center, Tokyo, Japan
| | - Hiromi Tagata
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan
| | - Tomoyuki Funatogawa
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan
| | - Taiju Yamaguchi
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan
| | - Naohisa Tsujino
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan; Department of Psychiatry, Saiseikai Yokohamashi Tobu Hospital, Kanagawa, Japan
| | - Masafumi Mizuno
- Department of Neuropsychiatry, Toho University Faculty of Medicine, Tokyo, Japan
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The relationship between cingulum bundle integrity and different aspects of executive functions in chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2020; 102:109955. [PMID: 32360815 DOI: 10.1016/j.pnpbp.2020.109955] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 03/19/2020] [Accepted: 04/28/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Evidence suggests that disruption in the cingulum bundle (CB) may influence executive dysfunctions in schizophrenia, but findings are still inconsistent. Using diffusion tensor imaging tractography, we investigated the differences in fiber integrity between schizophrenia patients and healthy controls together with the association between fiber integrity and executive functions. METHODS Thirty-two patients with chronic schizophrenia and 24 healthy controls took part in the study. Both groups were matched for age, sex, and years of education. Assessment of cognitive functions was performed using the Berg Card Sorting Test (BCST), the Color Trail Test (CTT), and the Stroop Color-Word Test (SCWT). RESULTS Results showed group differences, bilaterally (left and right) in fractional anisotropy (FA) of the CB, where patients showed less anisotropy than controls. Moreover, normal asymmetry (left FA > right FA) in the CB in schizophrenia was found. There were no group differences in mean diffusivity (MD). Patients had a similar but reduced profile of executive functions compared to healthy controls. However, when premorbid IQ was controlled for, the differences were no longer statistically significant. In schizophrenia patients, a negative correlation was found between FA of the left CB and perseverative errors in the BCST. CONCLUSIONS These findings provide evidence that CB disruption appears in schizophrenia patients and might account for impairments of executive processes, including concept formation.
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13
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Anterior cingulate morphology in people at genetic high-risk of schizophrenia. Eur Psychiatry 2020; 27:377-85. [DOI: 10.1016/j.eurpsy.2011.11.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Revised: 10/17/2011] [Accepted: 11/11/2011] [Indexed: 11/20/2022] Open
Abstract
AbstractBackgroundMorphological abnormalities of the anterior cingulate (AC) occur in patients with schizophrenia and in symptomatic high-risk individuals, and may be predictive of subsequent psychosis. We investigated AC sulcal morphology in the Edinburgh High Risk Study cohort to see if such abnormalities are evident and predict psychosis in patients’ relatives. We also investigated the association of the cingulate sulcus (CS) and paracingulate sulcus (PCS) variants with intelligence quotient (IQ).Patients and methodsWe compared cingulate and paracingulate sulcal anatomy, using reliable standardised measurements, blind to group membership, in those at high genetic risk (n = 146), first episode patients (n = 34) and healthy controls (n = 36); and compared high-risk subjects who did (n = 17) or did not develop schizophrenia.ResultsInterruptions of the cingulate sulcus were more common in high-risk individuals and in those with schizophrenia, in both hemispheres, compared to controls. When separated by gender, these results were only present in males in the left hemisphere and only in females in the right hemisphere. A well-formed paracingulate sulcus was less common in high-risk participants and patients with schizophrenia, compared to controls; but this association was only present in males. These morphological variants of the paracingulate sulcus and the continuous cingulate sulcus were also associated with the higher IQ in male high-risk individuals.ConclusionsAn interrupted cingulate sulcus pattern in both males and females and paracingulate morphology in males are associated with increased genetic risk of schizophrenia. Associations between cingulate and paracingulate morphology and premorbid IQ scores provide evidence that intellectual ability could be related to particular cytoarchitectural brain regions. Given that these sulci develop in early fetal life, such findings presumably reflect early neurodevelopmental abnormalities of genetic origin, although environmental effects and interactions cannot be ruled out.
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Moreno-López L, Ioannidis K, Askelund AD, Smith AJ, Schueler K, van Harmelen AL. The Resilient Emotional Brain: A Scoping Review of the Medial Prefrontal Cortex and Limbic Structure and Function in Resilient Adults With a History of Childhood Maltreatment. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2020; 5:392-402. [PMID: 32115373 DOI: 10.1016/j.bpsc.2019.12.008] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 11/18/2019] [Accepted: 12/06/2019] [Indexed: 12/20/2022]
Abstract
Childhood maltreatment (CM) is one of the strongest predictors of adult mental illness, although not all adults with CM develop psychopathology. Here, we describe the structure and function of the emotional brain regions that may contribute to resilient functioning after CM. We review studies that report medial prefrontal cortex, amygdala, and hippocampus (limbic regions) structure, function, and/or connections in resilient adults (i.e., those reporting CM without psychopathology) versus vulnerable adults (i.e., those reporting CM with psychopathology) or healthy adults (those without CM and with no psychopathology). We find that resilient adults have larger hippocampal gray and white matter volume and greater connectivity between the central executive network and the limbic regions. In addition, resilient adults have improved ability to regulate emotions through medial prefrontal cortex-limbic downregulation, lower hippocampal activation to emotional faces, and increased amygdala habituation to stress. We highlight the need for longitudinal designs that examine resilient functioning across domains and consider gender, type, timing, and nature of CM assessments and further stressors to further improve our understanding of the role of the emotional brain in resilient functioning after CM.
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Affiliation(s)
- Laura Moreno-López
- Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
| | - Konstantinos Ioannidis
- Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn, United Kingdom
| | | | - Alicia J Smith
- Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
| | - Katja Schueler
- Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Department of Psychology, Johannes Gutenberg-University Mainz, Mainz, Germany
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15
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Atypical lateralization in neurodevelopmental and psychiatric disorders: What is the role of stress? Cortex 2020; 125:215-232. [PMID: 32035318 DOI: 10.1016/j.cortex.2019.12.019] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 11/07/2019] [Accepted: 12/23/2019] [Indexed: 02/08/2023]
Abstract
Hemispheric asymmetries are a major organizational principle of the human brain. In different neurodevelopmental and psychiatric disorders, like schizophrenia, autism spectrum disorders, depression, dyslexia and posttraumatic stress disorder, functional and/or structural hemispheric asymmetries are altered compared to healthy controls. The question, why these disorders all share the common characteristic of altered hemispheric asymmetries despite vastly different etiologies and symptoms remains one of the unsolved mysteries of laterality research. This review is aimed at reviewing potential reasons for why atypical lateralization is so common in many neurodevelopmental and psychiatric disorders. To this end, we review the evidence for overlaps in the genetic and non-genetic factors involved in the ontogenesis of different disorders and hemispheric asymmetries. While there is evidence for genetic overlap between different disorders, only few asymmetry-related loci have also been linked to disorders and importantly, those effects are mostly specific to single disorders. However, there is evidence for shared non-genetic influences between disorders and hemispheric asymmetries. Most neurodevelopmental and psychiatric disorders show alterations in the hypothalamic-pituitary adrenocortical (HPA) axis and maternal as well as early life stress have been implicated in their etiology. Stress has also been suggested to affect hemispheric asymmetries. We propose a model in which early life stress as well as chronic stress not only increases the risk for psychiatric and neurodevelopmental disorders but also changes structural and functional hemispheric asymmetries leading to the aberrant lateralization patterns seen in these disorders. Thus, pathology-related changes in hemispheric asymmetries are not a factor causing disorders, but rather a different phenotype that is affected by partly overlapping ontogenetic factors, primarily stress.
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Fitzsimmons J, Rosa P, Sydnor VJ, Reid BE, Makris N, Goldstein JM, Mesholam-Gately RI, Woodberry K, Wojcik J, McCarley RW, Seidman LJ, Shenton ME, Kubicki M. Cingulum bundle abnormalities and risk for schizophrenia. Schizophr Res 2020; 215:385-391. [PMID: 31477373 DOI: 10.1016/j.schres.2019.08.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 07/22/2019] [Accepted: 08/15/2019] [Indexed: 01/13/2023]
Abstract
BACKGROUND The cingulum bundle (CB) is a major white matter fiber tract of the limbic system that underlies cingulate cortex, passing longitudinally over the corpus callosum. The connectivity of this white matter fiber tract plays a major role in emotional expression, attention, motivation, and working memory, all of which are affected in schizophrenia. Myelin related CB abnormalities have also been implicated in schizophrenia. The purpose of this study is to determine whether or not CB abnormalities are evident in individuals at clinical high risk (CHR) for psychosis, and whether or not cognitive deficits in the domains subserved by CB are related to its structural abnormalities. METHODS Diffusion Tensor Imaging (DTI) was performed on a 3 T magnet. DT tractography was used to evaluate CB in 20 individuals meeting CHR criteria (13 males/7 females) and 23 healthy controls (12 males/11 females) group matched on age, gender, parental socioeconomic status, education, and handedness. Fractional anisotropy (FA), a measure of white matter coherence and integrity, radial diffusivity (RD), thought to reflect myelin integrity, trace, a possible marker of atrophy, and axial diffusivity (AD), thought to reflect axonal integrity, were averaged over the entire tract and used to investigate CB abnormalities in individuals at CHR for psychosis compared with healthy controls. RESULTS Significant group differences were found between individuals at CHR for psychosis and controls for FA (p = 0.028), RD (p = 0.03) and trace (p = 0.031), but not for AD (p = 0.09). We did not find any significant correlations between DTI measures and clinical symptoms. CONCLUSION These findings suggest abnormalities (possibly myelin related) in the CB in individuals at CHR for psychosis.
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Affiliation(s)
- Jennifer Fitzsimmons
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
| | - Pedro Rosa
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Laboratory of Psychiatric Neuroimaging (LIM-21), Department & Institute of Psychiatry, Faculty of Medicine, Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Valerie J Sydnor
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Benjamin E Reid
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Nikos Makris
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Jill M Goldstein
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America
| | - Raquelle I Mesholam-Gately
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America
| | - Kristen Woodberry
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America
| | - Joanne Wojcik
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America
| | - Robert W McCarley
- Department of Psychiatry, VA Boston Healthcare System, Harvard Medical School, Boston, MA, United States of America
| | - Larry J Seidman
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Martha E Shenton
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Research and Development, VA Boston Healthcare System, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Marek Kubicki
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
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Koelkebeck K, Dannlowski U, Ohrmann P, Suslow T, Murai T, Bauer J, Pedersen A, Matsukawa N, Son S, Haidl T, Miyata J. Gray matter volume reductions in patients with schizophrenia: A replication study across two cultural backgrounds. Psychiatry Res Neuroimaging 2019; 292:32-40. [PMID: 31499256 DOI: 10.1016/j.pscychresns.2019.08.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/21/2019] [Accepted: 08/30/2019] [Indexed: 01/14/2023]
Abstract
Structural gray matter (GM) volume reductions in patients with schizophrenia have rarely been replicated across two different sites, the impact of culture and clinical characteristics remains unresolved. Hence, we assessed GM volume reductions in patients with schizophrenia using 3 T magnetic resonace imaging to replicate results across two independent and culturally different backgrounds (Germany, Japan), and to investigate the impact of brain volume reductions on clinical characteristics. In total, 163 German (80 patients) and 203 Japanese (83 patients) participants were included in the analysis. Voxel-based morphometry (VBM) was used to investigate structural differences between the groups and across the two sites, comparing local GM volumes. Clinical variables were used to analyze effects unrelated to the socio-cultural background. Across both data sets, widespread GM reductions in frontal and temporal cortical parts were found between patients and controls, indicating strong effects of diagnosis and only small effects of site. The investigation of clinical characteristics revealed the strongest effects for chlorpromazine equivalents on GM volume reductions primarily in the Japanese sample. Although the effects of site are small, several brain regions do not overlap between the two groups. Thus, GM may be affected differently at the two sites in patients with schizophrenia.
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Affiliation(s)
- Katja Koelkebeck
- Department of Psychiatry and Psychotherapy, University of Muenster, School of Medicine, Albert-Schweitzer-Campus 1, Building A9, 48149 Muenster, Germany.
| | - Udo Dannlowski
- Department of Psychiatry and Psychotherapy, University of Muenster, School of Medicine, Albert-Schweitzer-Campus 1, Building A9, 48149 Muenster, Germany
| | - Patricia Ohrmann
- Department of Psychiatry and Psychotherapy, University of Muenster, School of Medicine, Albert-Schweitzer-Campus 1, Building A9, 48149 Muenster, Germany
| | - Thomas Suslow
- University of Leipzig, Department of Psychosomatic Medicine and Psychotherapy, Semmelweisstrasse 10, 04103 Leipzig, Germany
| | - Toshiya Murai
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Jochen Bauer
- Institute of Clinical Radiology, Medical Faculty - University of Muenster - and University Hospital Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany
| | - Anya Pedersen
- Clinical Psychology and Psychotherapy, University of Kiel, Olshausenstrasse 62, 24118 Kiel, Germany
| | - Noriko Matsukawa
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Shuraku Son
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Theresa Haidl
- Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Strasse 62, 50934 Cologne, Germany
| | - Jun Miyata
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
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18
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Palaniyappan L, Al-Radaideh A, Mougin O, Das T, Gowland P, Liddle PF. Aberrant myelination of the cingulum and Schneiderian delusions in schizophrenia: a 7T magnetization transfer study. Psychol Med 2019; 49:1890-1896. [PMID: 30229713 DOI: 10.1017/s0033291718002647] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND The structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. More recently, aberrant myelination of frontal fasciculi, especially, cingulum has been proposed to underlie delayed corollary discharges that can affect sense of agency and contribute to delusions of control (Schneiderian delusions). Using the magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated the putative myelin content of cingulum bundle in patients with schizophrenia. METHODS Seventeen clinically stable patients with schizophrenia and 20 controls were recruited for this 7T MRI study. We used a region-of-interest method and extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum bundles and estimated patients v. controls differences. We also related the cingulum MTR values to the severity of Schneiderian delusions. RESULTS Patients had a significant reduction in the MTR, indicating reduced myelin content, in the cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The reduced MTR of left cingulum was associated with higher severity of Schneiderian delusions (τ = -0.45, p = 0.026) but no such relationship was seen for the right cingulum MTR (τ = -0.136, p = 0.50) among patients. The association between the left cingulum MTR and Schneiderian delusions was not explained by the presence of other delusions, hallucinations, disorganization or negative symptoms. CONCLUSIONS Dysmyelination of the cingulum bundle is seen in a subgroup of patients with schizophrenia and may be involved in the mechanism of Schneiderian delusions.
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Affiliation(s)
- Lena Palaniyappan
- Robarts Research Institute, University of Western Ontario,London, Ontario,Canada
| | - Ali Al-Radaideh
- Department of Medical Imaging, Faculty of Allied Health Sciences,The Hashemite University,Zarqa,Jordan
| | - Olivier Mougin
- Sir Peter Mansfield Imaging Centre (SPMIC), School of Physics and Astronomy, University of Nottingham,Nottingham,UK
| | - Tushar Das
- Robarts Research Institute, University of Western Ontario,London, Ontario,Canada
| | - Penny Gowland
- Sir Peter Mansfield Imaging Centre (SPMIC), School of Physics and Astronomy, University of Nottingham,Nottingham,UK
| | - Peter F Liddle
- Translational Neuroimaging for Mental Health, Division of Psychiatry and Applied Psychology,University of Nottingham,Nottingham,UK
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19
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Ahn SJ, Cornea E, Murphy V, Styner M, Jarskog LF, Gilmore JH. White matter development in infants at risk for schizophrenia. Schizophr Res 2019; 210:107-114. [PMID: 31182322 PMCID: PMC6689450 DOI: 10.1016/j.schres.2019.05.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 05/23/2019] [Accepted: 05/26/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Schizophrenia is considered a neurodevelopmental disorder with a pathophysiology that likely begins long before the onset of clinical symptoms. White matter abnormalities have been observed in schizophrenia and we hypothesized that the first 2 years of life is a period in which white matter abnormalities associated with schizophrenia risk may emerge. METHODS 38 infants at high risk for schizophrenia and 202 healthy controls underwent diffusion tensor MRIs after birth and at 1 and 2 years of age. Quantitative tractography was used to determine diffusion properties (fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD)) of 18 white matter tracts and a general linear model was used to analyze group differences at each age. RESULTS Adjusting gestational age at birth, postnatal age at MRI, gender, MRI scanner type, and maternal education, neonates at high risk had significantly lower FA (p = 0.02) and AD (p = 0.03) in the superior segment of the left cingulate, and higher RD in the hippocampal segment of the left cingulate (p = 0.04). High risk one year olds had significantly lower FA (p < 0.01) and AD (p = 0.02) in the hippocampal segment of the left cingulate. High risk two year olds had significantly lower FA in the left prefrontal cortico-thalamic tract (p = 0.04) and higher RD in the right uncinate fasciculus (p = 0.04). None of the tract differences remained significant after correction for multiple comparisons. CONCLUSIONS There is evidence of abnormal white matter development in young children at risk for schizophrenia, especially in the hippocampal segment of left cingulum. These results support the neurodevelopmental theory of schizophrenia and indicate that impaired white matter may be present in early childhood.
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Affiliation(s)
- Sung Jun Ahn
- Department of Radiology, Yonsei University College of Medicine, Seoul 06273, Korea
| | - Emil Cornea
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7160, USA
| | - Veronica Murphy
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7160, USA
| | - Martin Styner
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7160, USA,Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA
| | - L. Fredrik Jarskog
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7160, USA
| | - John H. Gilmore
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7160, USA
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20
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Kirino E, Hayakawa Y, Inami R, Inoue R, Aoki S. Simultaneous fMRI-EEG-DTI recording of MMN in patients with schizophrenia. PLoS One 2019; 14:e0215023. [PMID: 31071097 PMCID: PMC6508624 DOI: 10.1371/journal.pone.0215023] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 03/25/2019] [Indexed: 12/02/2022] Open
Abstract
Functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and diffusion tensor imaging (DTI) recording have complementary spatiotemporal resolution limitations but can be powerful methods when used together to enable both functional and anatomical modeling, with each neuroimaging procedure used to maximum advantage. We recorded EEGs during event-related fMRI followed by DTI in 15 healthy volunteers and 12 patients with schizophrenia using an omission mismatch negativity (MMN) paradigm. Blood oxygenation level-dependent (BOLD) signal changes were calculated in a region of interest (ROI) analysis, and fractional anisotropy (FA) in the white matter fibers related to each area was compared between groups using tract-specific analysis. Patients with schizophrenia had reduced BOLD activity in the left middle temporal gyrus, and BOLD activity in the right insula and right parahippocampal gyrus significantly correlated with positive symptoms on the Positive and Negative Syndrome Scale (PANSS) and hostility subscores. BOLD activation of Heschl’s gyri also correlated with the limbic system, including the insula. FA values in the left anterior cingulate cortex (ACC) significantly correlated with changes in the BOLD signal in the right superior temporal gyrus (STG), and FA values in the right ACC significantly correlated with PANSS scores. This is the first study to examine MMN using simultaneous fMRI, EEG, and DTI recording in patients with schizophrenia to investigate the potential implications of abnormalities in the ACC and limbic system, including the insula and parahippocampal gyrus, as well as the STG. Structural changes in the ACC during schizophrenia may represent part of the neural basis for the observed MMN deficits. The deficits seen in the feedback/feedforward connections between the prefrontal cortex and STG modulated by the ACC and insula may specifically contribute to impaired MMN generation and clinical manifestations.
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Affiliation(s)
- Eiji Kirino
- Department of Psychiatry, Juntendo University Shizuoka Hospital, Izunokuni City, Shizuoka, Japan
- Department of Psychiatry, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan
- Juntendo Institute of Mental Health, Fukuroyama, Koshigaya City, Saitama, Japan
- * E-mail:
| | - Yayoi Hayakawa
- Department of Radiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Rie Inami
- Department of Psychiatry, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan
| | - Reiichi Inoue
- Juntendo Institute of Mental Health, Fukuroyama, Koshigaya City, Saitama, Japan
| | - Shigeki Aoki
- Department of Radiology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan
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21
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Structural networks analysis for depression combined with graph theory and the properties of fiber tracts via diffusion tensor imaging. Neurosci Lett 2018; 694:34-40. [PMID: 30465819 DOI: 10.1016/j.neulet.2018.11.025] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 11/17/2018] [Accepted: 11/18/2018] [Indexed: 11/21/2022]
Abstract
Previous studies have suggested that major depressive disorder was associated with topological properties of impaired white matter. However, most related studies only use one property of nerve fibers to construct whole-brain structural brain network. Considering white matter changes variously, We hypothesized whether the alternations of white matter topological properties could reflect different impairment of white matter integrity. In addition, it is still unknown whether impaired integrity of the white matter fiber tracts has relationship with abnormal topological properties in MDD. This study investigated the impaired white matter by using graph theoretic analyses in a cohort of 37 MDD patients and 38 matched control subjects. In addition, we further investigated fiber tracts differences in three interregional connectivity matrixes of significant different topological regions in MDD. Our graph theoretic analyses demonstrated that 7 different regions were observed for the local measures in patients with MDD compared with control groups. These regions were the central nodes of cortical-limbic network, frontal-cingulate network, default mode network (DMN), cognitive control network(CCN)and affective network (AN). In addition, two impaired white matter pathways which included inferior longitudinal fasciculus (ILF) and cingulum were observed in MDD using fiber tracts analysis. We speculate impaired integrity of ILF is due to the alternations in the number of axons or myelination. The results further demonstrated that the number of fiber tracts of anterior cingulum was associated with the depression scores in MDD.
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22
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Alloza C, Cox SR, Blesa Cábez M, Redmond P, Whalley HC, Ritchie SJ, Muñoz Maniega S, Valdés Hernández MDC, Tucker-Drob EM, Lawrie SM, Wardlaw JM, Deary IJ, Bastin ME. Polygenic risk score for schizophrenia and structural brain connectivity in older age: A longitudinal connectome and tractography study. Neuroimage 2018; 183:884-896. [PMID: 30179718 PMCID: PMC6215331 DOI: 10.1016/j.neuroimage.2018.08.075] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 08/28/2018] [Accepted: 08/31/2018] [Indexed: 12/14/2022] Open
Abstract
Higher polygenic risk score for schizophrenia (szPGRS) has been associated with lower cognitive function and might be a predictor of decline in brain structure in apparently healthy populations. Age-related declines in structural brain connectivity-measured using white matter diffusion MRI -are evident from cross-sectional data. Yet, it remains unclear how graph theoretical metrics of the structural connectome change over time, and whether szPGRS is associated with differences in ageing-related changes in human brain connectivity. Here, we studied a large, relatively healthy, same-year-of-birth, older age cohort over a period of 3 years (age ∼ 73 years, N = 731; age ∼76 years, N = 488). From their brain scans we derived tract-averaged fractional anisotropy (FA) and mean diffusivity (MD), and network topology properties. We investigated the cross-sectional and longitudinal associations between these structural brain variables and szPGRS. Higher szPGRS showed significant associations with longitudinal increases in MD in the splenium (β = 0.132, pFDR = 0.040), arcuate (β = 0.291, pFDR = 0.040), anterior thalamic radiations (β = 0.215, pFDR = 0.040) and cingulum (β = 0.165, pFDR = 0.040). Significant declines over time were observed in graph theory metrics for FA-weighted networks, such as mean edge weight (β = -0.039, pFDR = 0.048) and strength (β = -0.027, pFDR = 0.048). No significant associations were found between szPGRS and graph theory metrics. These results are consistent with the hypothesis that szPGRS confers risk for ageing-related degradation of some aspects of structural connectivity.
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Affiliation(s)
- C Alloza
- Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
| | - S R Cox
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) Collaboration, University of Edinburgh, Edinburgh, UK
| | - M Blesa Cábez
- MRC Centre for Reproductive Health, University of Edinburgh, UK
| | - P Redmond
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK
| | - H C Whalley
- Division of Psychiatry, University of Edinburgh, Edinburgh, UK
| | - S J Ritchie
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK
| | - S Muñoz Maniega
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) Collaboration, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - M Del C Valdés Hernández
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) Collaboration, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - E M Tucker-Drob
- Department of Psychology, University of Texas, Austin, TX, USA
| | - S M Lawrie
- Division of Psychiatry, University of Edinburgh, Edinburgh, UK
| | - J M Wardlaw
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) Collaboration, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - I J Deary
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK
| | - M E Bastin
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) Collaboration, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
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23
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Bubb EJ, Metzler-Baddeley C, Aggleton JP. The cingulum bundle: Anatomy, function, and dysfunction. Neurosci Biobehav Rev 2018; 92:104-127. [PMID: 29753752 PMCID: PMC6090091 DOI: 10.1016/j.neubiorev.2018.05.008] [Citation(s) in RCA: 495] [Impact Index Per Article: 70.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 05/01/2018] [Accepted: 05/04/2018] [Indexed: 12/16/2022]
Abstract
The cingulum bundle is a prominent white matter tract that interconnects frontal, parietal, and medial temporal sites, while also linking subcortical nuclei to the cingulate gyrus. Despite its apparent continuity, the cingulum's composition continually changes as fibres join and leave the bundle. To help understand its complex structure, this review begins with detailed, comparative descriptions of the multiple connections comprising the cingulum bundle. Next, the impact of cingulum bundle damage in rats, monkeys, and humans is analysed. Despite causing extensive anatomical disconnections, cingulum bundle lesions typically produce only mild deficits, highlighting the importance of parallel pathways and the distributed nature of its various functions. Meanwhile, non-invasive imaging implicates the cingulum bundle in executive control, emotion, pain (dorsal cingulum), and episodic memory (parahippocampal cingulum), while clinical studies reveal cingulum abnormalities in numerous conditions, including schizophrenia, depression, post-traumatic stress disorder, obsessive compulsive disorder, autism spectrum disorder, Mild Cognitive Impairment, and Alzheimer's disease. Understanding the seemingly diverse contributions of the cingulum will require better ways of isolating pathways within this highly complex tract.
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Affiliation(s)
- Emma J Bubb
- School of Psychology, Cardiff University, 70 Park Place, Cardiff, CF10 3AT, Wales, UK
| | | | - John P Aggleton
- School of Psychology, Cardiff University, 70 Park Place, Cardiff, CF10 3AT, Wales, UK.
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24
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Zhang Z, Yan T, Wang Y, Zhang Q, Zhao W, Chen X, Zhai J, Chen M, Du B, Deng X, Ji F, Xiang Y, Wu H, Song J, Dong Q, Chen C, Li J. Polymorphism in schizophrenia risk gene MIR137 is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls. NEUROIMAGE-CLINICAL 2018; 19:160-166. [PMID: 30035013 PMCID: PMC6051762 DOI: 10.1016/j.nicl.2018.03.039] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 03/16/2018] [Accepted: 03/31/2018] [Indexed: 12/02/2022]
Abstract
MIR137 gene has been repeatedly reported as a schizophrenia risk gene in genome-wide association studies (GWAS). A polymorphism (rs1625579) at the MIR137 gene has been associated with both neural activation and behavioral performance during a working memory task. This study examined MIR137's associations with task-related (N-back working memory) fMRI, resting state fMRI, and diffusion tensor images (DTI) data in 177 healthy adults. We found less deactivation of the PCC in risk allele homozygotes (TT) as compared to the GT heterozygotes (cluster size = 630 voxels, cluster level PFWE < 0.001) during the N-back task, which replicated previous findings. Using the identified cluster within the PCC as the seed, we further found decreased functional connectivity between the PCC and the anterior cingulate cortex and its adjacent medial prefrontal cortex (ACC/MPFC) in risk allele homozygotes during both resting state (cluster size = 427 voxels, cluster level PFWE = 0.001) and the N-back task (cluster size = 73 voxels, cluster level PFWE = 0.05). Finally, an analysis of our DTI data showed decreased white matter integrity of the posterior cingulum in risk allele homozygotes (cluster size = 214 voxels, cluster level PFWE = 0.03). Taken together, rs1625579 seems to play an important role in both functional and structural connectivity between the PCC and the ACC/MPFC, which may serve as the brain mechanisms for the link between rs1625579 and schizophrenia.
This study replicated the association between the risk allele of rs1625579 and altered activations at the PCC. This study found decreased functional connectivity between the PCC and the ACC/MPFC in the risk allele homozygotes. This study found decreased FA value in the posterior cingulum in the risk allele homozygotes.
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Affiliation(s)
- Zhifang Zhang
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Tongjun Yan
- The PLA 102nd Hospital and Mental Health Center of Military, Changzhou 213003, PR China
| | - Yanyan Wang
- The PLA 102nd Hospital and Mental Health Center of Military, Changzhou 213003, PR China
| | - Qiumei Zhang
- School of Mental Health, Jining Medical University, 45# Jianshe South Road, Jining 272013, Shandong Province, PR China; State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Wan Zhao
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Xiongying Chen
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Jinguo Zhai
- School of Mental Health, Jining Medical University, 45# Jianshe South Road, Jining 272013, Shandong Province, PR China
| | - Min Chen
- School of Mental Health, Jining Medical University, 45# Jianshe South Road, Jining 272013, Shandong Province, PR China
| | - Boqi Du
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Xiaoxiang Deng
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Feng Ji
- School of Mental Health, Jining Medical University, 45# Jianshe South Road, Jining 272013, Shandong Province, PR China
| | - Yutao Xiang
- Beijing Anding Hospital, Beijing 100088, PR China; Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau
| | - Hongjie Wu
- Shengli Hospital of Shengli Petroleum Administration Bureau, Dongying 257022, Shandong Province, PR China
| | - Jie Song
- Shengli Hospital of Shengli Petroleum Administration Bureau, Dongying 257022, Shandong Province, PR China
| | - Qi Dong
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China
| | - Chuansheng Chen
- Department of Psychology and Social Behavior, University of California, Irvine, CA 92697, United States
| | - Jun Li
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, PR China.
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Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy. Eur Arch Psychiatry Clin Neurosci 2018; 268:89-98. [PMID: 27942861 DOI: 10.1007/s00406-016-0752-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 02/06/2016] [Indexed: 01/27/2023]
Abstract
Intermediate phenotype could be used to investigate genetic susceptibility. However, genetic and environmental heterogeneity may interfere with identification of intermediate phenotypes. In this study, we minimized these interferences by using a novel group strategy. A total of 22 drug-naive and first-episode schizophrenia (FES) patients, along with 22 of their kin healthy siblings (HS), 22 non-kin healthy siblings (nHS) of other schizophrenia patients and 22 healthy controls (HC), were recruited. Brain imaging was acquired from the participants. Voxel-based analysis was used to investigate differences in white matter integrity derived from diffusion tensor imaging among the four groups. Two cognitive tests related to our findings were selected to confirm the related phenotypic changes. All of the FES, HS, and nHS groups showed decreased fractional anisotropy (FA) values in the left inferior frontal gyrus (IFG) compared with the HC group (p < 0.05, FDR corrected). The scores of Hopkins Verbal learning Test-Revised and Animal Naming in FES patients were significantly lower than in participants belonging to the other three groups (p < 0.05). Significant correlation between Animal Naming scores and FA values in the left IFG was found in FES patients (r = 0.53, p = 0.01). Moreover, FES patients also showed decreased FA values in the left medial frontal gyrus, left inferior temporal gyrus, left parahippocampal gyrus, left posterior cingulate, and right middle temporal gyrus compared with HC (p < 0.05, FDR corrected). Decreased FA values in the left IFG is a possible intermediate phenotype of schizophrenia, and this finding supports the hypothesis that disrupted connectivity of white matter may be the key substrate of schizophrenia.
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Ribolsi M, Lisi G, Ponzo V, Siracusano A, Caltagirone C, Niolu C, Koch G. Left hemispheric breakdown of LTP-like cortico-cortical plasticity in schizophrenic patients. Clin Neurophysiol 2017; 128:2037-2042. [DOI: 10.1016/j.clinph.2017.06.255] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Revised: 05/21/2017] [Accepted: 06/26/2017] [Indexed: 12/23/2022]
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27
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Takiguchi K, Uezato A, Itasaka M, Atsuta H, Narushima K, Yamamoto N, Kurumaji A, Tomita M, Oshima K, Shoda K, Tamaru M, Nakataki M, Okazaki M, Ishiwata S, Ishiwata Y, Yasuhara M, Arima K, Ohmori T, Nishikawa T. Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study. BMC Psychiatry 2017; 17:249. [PMID: 28701225 PMCID: PMC5508614 DOI: 10.1186/s12888-017-1410-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 06/29/2017] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. RESULTS D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. CONCLUSION It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. TRIAL REGISTRATION UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.
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Affiliation(s)
- Kazuo Takiguchi
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan ,Haryugaoka Hospital, Tensyoudan 11, Otsukimachi, Koriyama-shi, Fukushima, 963-0201 Japan
| | - Akihito Uezato
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Michio Itasaka
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Hidenori Atsuta
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Kenji Narushima
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Naoki Yamamoto
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan ,0000 0004 0378 2239grid.417089.3Psychiatry Department, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu-shi, Tokyo, 183-8524 Japan
| | - Akeo Kurumaji
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Makoto Tomita
- 0000 0001 1014 9130grid.265073.5Clinical Research Center, Medical Hospital of Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Kazunari Oshima
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan ,Ohmiya Kousei Hospital, Katayanagi 1, Minuma-ku, Saitama-shi, Saitama, 337-0024 Japan
| | - Kosaku Shoda
- Ohmiya Kousei Hospital, Katayanagi 1, Minuma-ku, Saitama-shi, Saitama, 337-0024 Japan
| | - Mai Tamaru
- 0000 0001 1092 3579grid.267335.6Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503 Japan
| | - Masahito Nakataki
- 0000 0001 1092 3579grid.267335.6Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503 Japan
| | - Mitsutoshi Okazaki
- Department of Psychiatry, National Center Hospital of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo, 187-8551 Japan
| | - Sayuri Ishiwata
- 0000 0001 1014 9130grid.265073.5Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Yasuyoshi Ishiwata
- 0000 0001 1014 9130grid.265073.5Department of Hospital Pharmacy, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Masato Yasuhara
- 0000 0001 1014 9130grid.265073.5Department of Hospital Pharmacy, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan
| | - Kunimasa Arima
- Department of Psychiatry, National Center Hospital of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo, 187-8551 Japan
| | - Tetsuro Ohmori
- 0000 0001 1092 3579grid.267335.6Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto, Tokushima, 770-8503 Japan
| | - Toru Nishikawa
- Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
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Zhao X, Sui Y, Yao J, Lv Y, Zhang X, Jin Z, Chen L, Zhang X. Reduced white matter integrity and facial emotion perception in never-medicated patients with first-episode schizophrenia: A diffusion tensor imaging study. Prog Neuropsychopharmacol Biol Psychiatry 2017; 77:57-64. [PMID: 28385492 DOI: 10.1016/j.pnpbp.2017.03.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 03/08/2017] [Accepted: 03/27/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND Facial emotion perception is impaired in schizophrenia. Although the pathology of schizophrenia is thought to involve abnormality in white matter (WM), few studies have examined the correlation between facial emotion perception and WM abnormalities in never-medicated patients with first-episode schizophrenia. The present study tested associations between facial emotion perception and WM integrity in order to investigate the neural basis of impaired facial emotion perception in schizophrenia. METHODS Sixty-three schizophrenic patients and thirty control subjects underwent facial emotion categorization (FEC). The FEC data was inserted into a logistic function model with subsequent analysis by independent-samples T test and the shift point and slope as outcome measurements. Severity of symptoms was measured using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). Voxelwise group comparison of WM fractional anisotropy (FA) was operated using tract-based spatial statistics (TBSS). The correlation between impaired facial emotion perception and FA reduction was examined in patients using simple regression analysis within brain areas that showed a significant FA reduction in patients compared with controls. The same correlation analysis was also performed for control subjects in the whole brain. RESULTS The patients with schizophrenia reported a higher shift point and a steeper slope than control subjects in FEC. The patients showed a significant FA reduction in left deep WM in the parietal, temporal and occipital lobes, a small portion of the corpus callosum (CC), and the corona radiata. In voxelwise correlation analysis, we found that facial emotion perception significantly correlated with reduced FA in various WM regions, including left forceps major (FM), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), Left splenium of CC, and left ILF. The correlation analyses in healthy controls revealed no significant correlation of FA with FEC task. CONCLUSIONS These results showed disrupted WM integrity in these regions constitutes a potential neural basis for the facial emotion perception impairments in schizophrenia.
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Affiliation(s)
- Xiaoxin Zhao
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Yuxiu Sui
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China..
| | - Jingjing Yao
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Yiding Lv
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Xinyue Zhang
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Zhuma Jin
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Lijun Chen
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Xiangrong Zhang
- Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, China
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29
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Schizophrenia symptomatic associations with diffusion tensor imaging measured fractional anisotropy of brain: a meta-analysis. Neuroradiology 2017; 59:699-708. [PMID: 28550466 DOI: 10.1007/s00234-017-1844-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 05/02/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE Several studies have examined the relationships between diffusion tensor imaging (DTI)-measured fractional anisotropy (FA) and the symptoms of schizophrenia, but results vary across the studies. The aim of this study was to carry out a meta-analysis of correlation coefficients reported by relevant studies to evaluate the correlative relationships between FA of various parts of the brain and schizophrenia symptomatic assessments. METHODS Literature was searched in several electronic databases, and study selection was based on précised eligibility criteria. Correlation coefficients between FA of a part of the brain and schizophrenia symptom were first converted into Fisher's z-scores for meta-analyses, and then overall effect sizes were back transformed to correlation coefficients. RESULTS Thirty-three studies (1121 schizophrenia patients; age 32.66 years [95% confidence interval (CI) 30.19, 35.13]; 65.95 % [57.63, 74.28] males) were included in this meta-analysis. Age was inversely associated with brain FA (z-scores [95% CI] -0.23 [-0.14, -0.32]; p ˂ 0.00001). Brain FA of various areas was inversely associated with negative symptoms of schizophrenia (z-score -0.30 [-0.23, -0.36]; p ˂ 0.00001) but was positively associated with positive symptoms of schizophrenia (z-score 0.16 [0.04, 0.27]; p = 0.007) and general psychopathology of schizophrenia (z-score 0.26 [0.15, 0.37]; p = 0.00001). CONCLUSION Although, DTI-measured brain FA is found to be inversely associated with negative symptoms and positively associated with positive symptoms and general psychopathology of schizophrenia, the effect sizes of these correlations are low and may not be clinically significant. Moreover, brain FA was also negatively associated with age of patients.
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30
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Asmal L, du Plessis S, Vink M, Fouche JP, Chiliza B, Emsley R. Insight and white matter fractional anisotropy in first-episode schizophrenia. Schizophr Res 2017; 183:88-94. [PMID: 27887780 DOI: 10.1016/j.schres.2016.11.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 11/04/2016] [Accepted: 11/07/2016] [Indexed: 12/22/2022]
Abstract
Impaired insight is a hallmark feature of schizophrenia. Structural studies implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior temporal brain regions. The cortical midline structures (CMS) are also implicated in functional studies primarily through self-reflective processing tasks. However, few studies have explored the relationship between white matter tracts and insight in schizophrenia, and none in first-episode schizophrenia (FES). Here, we examined for fractional anisotropy (FA) differences in 89 minimally treated FES patients and 98 matched controls, and identified those FA differences associated with impaired clinical insight in patients. We found widespread FA reduction in FES patients compared to controls. Poorer insight in patients was predicted by lower FA values in a number of white matter tracts with a predilection for tracts associated with cortical midline structures (fronto-occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata), and more severe depressive symptoms. The association between FA abnormalities and insight was most robust for the awareness of symptoms and illness awareness domains. Our study implicates a network of tracts involved in impaired insight in schizophrenia with a predilection for the CMS. This study is a first step in delineating the white matter tracts involved in insight impairment in schizophrenia prior to chronicity.
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Affiliation(s)
- Laila Asmal
- Stellenbosch University, Faculty of Medicine and Health Sciences, Psychiatry, PO Box 19063, Tygerberg, Cape Town ZA 7505, South Africa.
| | - Stefan du Plessis
- Stellenbosch University, Faculty of Medicine and Health Sciences, Psychiatry, PO Box 19063, Tygerberg, Cape Town ZA 7505, South Africa
| | - Matthijs Vink
- Departments of Developmental and Experimental Psychology, Utrecht University, Utrecht, The Netherlands
| | - Jean-Paul Fouche
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town ZA 8001, South Africa
| | - Bonginkosi Chiliza
- Stellenbosch University, Faculty of Medicine and Health Sciences, Psychiatry, PO Box 19063, Tygerberg, Cape Town ZA 7505, South Africa
| | - Robin Emsley
- Stellenbosch University, Faculty of Medicine and Health Sciences, Psychiatry, PO Box 19063, Tygerberg, Cape Town ZA 7505, South Africa
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31
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Klauser P, Baker ST, Cropley VL, Bousman C, Fornito A, Cocchi L, Fullerton JM, Rasser P, Schall U, Henskens F, Michie PT, Loughland C, Catts SV, Mowry B, Weickert TW, Shannon Weickert C, Carr V, Lenroot R, Pantelis C, Zalesky A. White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs. Schizophr Bull 2017; 43:425-435. [PMID: 27535082 PMCID: PMC5605265 DOI: 10.1093/schbul/sbw100] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles.
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Affiliation(s)
- Paul Klauser
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia;,Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia;,Lausanne University Hospital, Department of Psychiatry, Prilly, Switzerland
| | - Simon T. Baker
- Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia
| | - Vanessa L. Cropley
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
| | - Chad Bousman
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia;,Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Alex Fornito
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia;,Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia
| | - Luca Cocchi
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Janice M. Fullerton
- Neuroscience Research Australia, Randwick, New South Wales, Australia;,School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
| | - Paul Rasser
- Centre for Brain and Mental Health Research, University of Newcastle, Waratah, New South Wales, Australia;,Hunter Medical Research Institute, Newcastle, New South Wales, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia
| | - Ulrich Schall
- Centre for Brain and Mental Health Research, University of Newcastle, Waratah, New South Wales, Australia;,Hunter Medical Research Institute, Newcastle, New South Wales, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia
| | - Frans Henskens
- School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, New South Wales, Australia
| | - Patricia T. Michie
- Centre for Brain and Mental Health Research, University of Newcastle, Waratah, New South Wales, Australia;,Hunter Medical Research Institute, Newcastle, New South Wales, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia;,School of Psychology, University of Newcastle, Callaghan, New South Wales, Australia
| | - Carmel Loughland
- Neuroscience Research Australia, Randwick, New South Wales, Australia;,Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia
| | - Stanley V. Catts
- School of Medicine, The University of Queensland, Brisbane, Qeensland, Australia
| | - Bryan Mowry
- Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia;,Queensland Centre for Mental Health Research, The University of Queensland, Brisbane, Queensland, Australia
| | - Thomas W. Weickert
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia;,Neuroscience Research Australia, Randwick, New South Wales, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia;,School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
| | - Cynthia Shannon Weickert
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia;,Neuroscience Research Australia, Randwick, New South Wales, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia;,School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
| | - Vaughan Carr
- Schizophrenia Research Institute, Randwick, New South Wales, Australia;,School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia;,Department of Psychiatry, Monash University, Clayton, Victoria, Australia
| | - Rhoshel Lenroot
- Neuroscience Research Australia, Randwick, New South Wales, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia;,School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia;,Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia;,Schizophrenia Research Institute, Randwick, New South Wales, Australia;,Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, Victoria, Australia
| | - Andrew Zalesky
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia
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Docx L, Emsell L, Van Hecke W, De Bondt T, Parizel PM, Sabbe B, Morrens M. White matter microstructure and volitional motor activity in schizophrenia: A diffusion kurtosis imaging study. Psychiatry Res Neuroimaging 2017; 260:29-36. [PMID: 28012424 DOI: 10.1016/j.pscychresns.2016.10.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 09/18/2016] [Accepted: 10/14/2016] [Indexed: 12/13/2022]
Abstract
Avolition is a core feature of schizophrenia and may arise from altered brain connectivity. Here we used diffusion kurtosis imaging (DKI) to investigate the association between white matter (WM) microstructure and volitional motor activity. Multi-shell diffusion MRI and 24-h actigraphy data were obtained from 20 right-handed patients with schizophrenia and 16 right-handed age and gender matched healthy controls. We examined correlations between fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and motor activity level, as well as group differences in these measures. In the patient group, increasing motor activity level was positively correlated with MK in the inferior, medial and superior longitudinal fasciculus, the corpus callosum, the posterior fronto-occipital fasciculus and the posterior cingulum. This association was not found in control subjects or in DTI measures. These results show that a lack of volitional motor activity in schizophrenia is associated with potentially altered WM microstructure in posterior brain regions associated with cognitive function and motivation. This could reflect both illness related dysconnectivity which through altered cognition, manifests as reduced volitional motor activity, and/or the effects of reduced physical activity on brain WM.
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Affiliation(s)
- Lise Docx
- Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; PC Broeders Alexianen Boechout, Provinciesteenweg 408, 2530 Boechout, Belgium.
| | - Louise Emsell
- University Psychiatry Centre (UPC)-KU Leuven, Leuven, Belgium
| | - Wim Van Hecke
- Department of Radiology, Antwerp University Hospital & University of Antwerp, Antwerp, Belgium
| | - Timo De Bondt
- Department of Radiology, Antwerp University Hospital & University of Antwerp, Antwerp, Belgium
| | - Paul M Parizel
- Department of Radiology, Antwerp University Hospital & University of Antwerp, Antwerp, Belgium
| | - Bernard Sabbe
- Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; PZ St Norbertus Duffel, Stationsstraat 25c, 2570 Duffel, Belgium
| | - Manuel Morrens
- Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium; PC Broeders Alexianen Boechout, Provinciesteenweg 408, 2530 Boechout, Belgium
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33
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Domen P, Peeters S, Michielse S, Gronenschild E, Viechtbauer W, Roebroeck A, Os JV, Marcelis M. Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study. Schizophr Bull 2017; 43:160-170. [PMID: 27190279 PMCID: PMC5216846 DOI: 10.1093/schbul/sbw061] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
BACKGROUND Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. METHODS Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models. RESULTS Siblings revealed a significant mean FA decrease over time compared to controls (B = -0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = -0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group × region interaction (χ2 = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata. CONCLUSION Whole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations.
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Affiliation(s)
- Patrick Domen
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands;
| | - Sanne Peeters
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
- Faculty of Psychology and Educational Sciences, Open University of the Netherlands, Heerlen, The Netherlands
| | - Stijn Michielse
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Ed Gronenschild
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Wolfgang Viechtbauer
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Alard Roebroeck
- Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Jim van Os
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
- King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, UK
| | - Machteld Marcelis
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
- Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, The Netherlands
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34
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Simner J, Rehme M, Carmichael D, Bastin M, Sprooten E, McIntosh A, Lawrie S, Zedler M. Social responsiveness to inanimate entities: Altered white matter in a ‘social synaesthesia’. Neuropsychologia 2016; 91:282-289. [DOI: 10.1016/j.neuropsychologia.2016.08.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 08/10/2016] [Accepted: 08/18/2016] [Indexed: 12/23/2022]
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35
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Gay O, Plaze M, Oppenheim C, Gaillard R, Olié JP, Krebs MO, Cachia A. Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development. J Psychiatry Neurosci 2016; 41:150267. [PMID: 27673502 PMCID: PMC5373705 DOI: 10.1503/jpn.150267] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 02/10/2016] [Accepted: 05/16/2016] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia. METHODS We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement. RESULTS We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology (p = 0.041) as well as interactions between NSS and ACC morphology (p = 0.005), between NSS and handedness (p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume (p = 0.005) on CC measured using the TMT-B score - the TMT-A score. LIMITATIONS No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis. CONCLUSION To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms.
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Affiliation(s)
- Olivier Gay
- From the INSERM UMR 894, Centre de Psychiatrie & Neurosciences, CNRS GDR 3557, Institut de Psychiatrie, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Université Paris Descartes, Sorbonne Paris Cité, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France (Gay, Plaze, Gaillard, Olié, Krebs); the Service d’Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France (Oppenheim); the CNRS UMR 8240, Laboratoire de Psychologie du Développement et de l’Éducation de l’Enfant, Paris, France (Cachia); and the Institut Universitaire de France, Paris, France (Cachia)
| | - Marion Plaze
- From the INSERM UMR 894, Centre de Psychiatrie & Neurosciences, CNRS GDR 3557, Institut de Psychiatrie, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Université Paris Descartes, Sorbonne Paris Cité, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France (Gay, Plaze, Gaillard, Olié, Krebs); the Service d’Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France (Oppenheim); the CNRS UMR 8240, Laboratoire de Psychologie du Développement et de l’Éducation de l’Enfant, Paris, France (Cachia); and the Institut Universitaire de France, Paris, France (Cachia)
| | - Catherine Oppenheim
- From the INSERM UMR 894, Centre de Psychiatrie & Neurosciences, CNRS GDR 3557, Institut de Psychiatrie, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Université Paris Descartes, Sorbonne Paris Cité, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France (Gay, Plaze, Gaillard, Olié, Krebs); the Service d’Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France (Oppenheim); the CNRS UMR 8240, Laboratoire de Psychologie du Développement et de l’Éducation de l’Enfant, Paris, France (Cachia); and the Institut Universitaire de France, Paris, France (Cachia)
| | - Raphael Gaillard
- From the INSERM UMR 894, Centre de Psychiatrie & Neurosciences, CNRS GDR 3557, Institut de Psychiatrie, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Université Paris Descartes, Sorbonne Paris Cité, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France (Gay, Plaze, Gaillard, Olié, Krebs); the Service d’Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France (Oppenheim); the CNRS UMR 8240, Laboratoire de Psychologie du Développement et de l’Éducation de l’Enfant, Paris, France (Cachia); and the Institut Universitaire de France, Paris, France (Cachia)
| | - Jean-Pierre Olié
- From the INSERM UMR 894, Centre de Psychiatrie & Neurosciences, CNRS GDR 3557, Institut de Psychiatrie, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Université Paris Descartes, Sorbonne Paris Cité, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France (Gay, Plaze, Gaillard, Olié, Krebs); the Service d’Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France (Oppenheim); the CNRS UMR 8240, Laboratoire de Psychologie du Développement et de l’Éducation de l’Enfant, Paris, France (Cachia); and the Institut Universitaire de France, Paris, France (Cachia)
| | | | - Arnaud Cachia
- Correspondence to: Prof. A. Cachia, Centre de Psychiatrie et Neurosciences, UMR 894, INSERM – Université, Paris Descartes, Hôpital Sainte-Anne, Paris, France;
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Chekouo T, Stingo FC, Guindani M, Do KA. A Bayesian predictive model for imaging genetics with application to schizophrenia. Ann Appl Stat 2016. [DOI: 10.1214/16-aoas948] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Oestreich LKL, Pasternak O, Shenton ME, Kubicki M, Gong X, McCarthy-Jones S, Whitford TJ. Abnormal white matter microstructure and increased extracellular free-water in the cingulum bundle associated with delusions in chronic schizophrenia. NEUROIMAGE-CLINICAL 2016; 12:405-14. [PMID: 27622137 PMCID: PMC5008040 DOI: 10.1016/j.nicl.2016.08.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 07/01/2016] [Accepted: 08/03/2016] [Indexed: 12/22/2022]
Abstract
Background There is growing evidence to suggest that delusions associated with schizophrenia arise from altered structural brain connectivity. The present study investigated whether structural changes in three major fasciculi that interconnect the limbic system – the cingulum bundle, uncinate fasciculus and fornix – are associated with delusions in chronic schizophrenia patients. Methods Free-water corrected Diffusion Tensor Imaging was used to investigate the association between delusions and both microstructural changes within these three fasciculi and extracellular changes in the surrounding free-water. Clinical data and diffusion MRI scans were obtained from 28 healthy controls and 86 schizophrenia patients, of whom 34 had present state delusions, 35 had a lifetime history but currently remitted delusions, and 17 had never experienced delusions. Results While present state and remitted delusions were found to be associated with reduced free-water corrected fractional anisotropy (FAT) and increased free-water corrected radial diffusivity (RDT) in the cingulum bundle bilaterally, extracellular free-water (FW) in the left cingulum bundle was found to be specifically associated with present state delusions in chronic schizophrenia. No changes were observed in the remaining tracts. Conclusions These findings suggest that state and trait delusions in chronic schizophrenia are associated with microstructural processes, such as myelin abnormalities (as indicated by decreased FAT and increased RDT) in the cingulum bundle and that state delusions are additionally associated with extracellular processes such as neuroinflammation or atrophy (as indicated by increased FW) in the left cingulum bundle.
Free-water imaging was used to differentiate microstructural and extracellular processes. Patients with delusions showed increased RDT and FW in the cingulum bundle. Myelin abnormalities and neuroinflammation may be involved in the manifestation of delusions.
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Affiliation(s)
- Lena K L Oestreich
- School of Psychology, UNSW Australia, NSW, Australia; Queensland Brain Institute, University of Queensland, St Lucia, QLD 4072, Australia
| | - Ofer Pasternak
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Martha E Shenton
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA
| | - Marek Kubicki
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Xue Gong
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Simon McCarthy-Jones
- Department of Cognitive Science, Macquarie University, NSW, Australia; Department of Psychiatry, Trinity College Dublin, Ireland
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Seitz J, Zuo JX, Lyall AE, Makris N, Kikinis Z, Bouix S, Pasternak O, Fredman E, Duskin J, Goldstein JM, Petryshen TL, Mesholam-Gately RI, Wojcik J, McCarley RW, Seidman LJ, Shenton ME, Koerte IK, Kubicki M. Tractography Analysis of 5 White Matter Bundles and Their Clinical and Cognitive Correlates in Early-Course Schizophrenia. Schizophr Bull 2016; 42:762-71. [PMID: 27009248 PMCID: PMC4838095 DOI: 10.1093/schbul/sbv171] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
PURPOSE Tractography is the most anatomically accurate method for delineating white matter tracts in the brain, yet few studies have examined multiple tracts using tractography in patients with schizophrenia (SCZ). We analyze 5 white matter connections important in the pathophysiology of SCZ: uncinate fasciculus, cingulum bundle (CB), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus, and arcuate fasciculus (AF). Additionally, we investigate the relationship between diffusion tensor imaging (DTI) markers and neuropsychological measures. METHODS High-resolution DTI data were acquired on a 3 Tesla scanner in 30 patients with early-course SCZ and 30 healthy controls (HC) from the Boston Center for Intervention Development and Applied Research study. After manually guided tracts delineation, fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD) were calculated and averaged along each tract. The association of DTI measures with the Scales for the Assessment of Negative and Positive Symptoms and neuropsychological measures was evaluated. RESULTS Compared to HC, patients exhibited reduced FA and increased trace and RD in the right AF, CB, and ILF. A discriminant analysis showed the possible use of FA of these tracts for better future group membership classifications. FA and RD of the right ILF and AF were associated with positive symptoms while FA and RD of the right CB were associated with memory performance and processing speed. CONCLUSION We observed white matter alterations in the right CB, ILF, and AF, possibly caused by myelin disruptions. The structural abnormalities interact with cognitive performance, and are linked to clinical symptoms.
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Affiliation(s)
- Johanna Seitz
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
| | - Jessica X. Zuo
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Amanda E. Lyall
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Nikos Makris
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA;,Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA
| | - Zora Kikinis
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Sylvain Bouix
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Ofer Pasternak
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Eli Fredman
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Jonathan Duskin
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Jill M. Goldstein
- Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA;,Department of Medicine, Connors Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Tracey L. Petryshen
- Department of Psychiatry and Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetic Unit, Massachusetts General Hospital, Boston, MA;,Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA
| | - Raquelle I. Mesholam-Gately
- Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Joanne Wojcik
- Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Robert W. McCarley
- Department of Psychiatry, Laboratory of Neuroscience, Clinical Neuroscience Division, VA Boston Healthcare System, Brockton, MA
| | - Larry J. Seidman
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA;,Department of Psychiatry, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Martha E. Shenton
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,VA Boston Healthcare System, Brockton Division, Brockton, MA
| | - Inga K. Koerte
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;,Department of Child and Adolescent Psychiatry, Psychosomatic and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
| | - Marek Kubicki
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
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Zhang C, Hu WH, Wu DL, Zhang K, Zhang JG. Behavioral effects of deep brain stimulation of the anterior nucleus of thalamus, entorhinal cortex and fornix in a rat model of Alzheimer's disease. Chin Med J (Engl) 2016; 128:1190-5. [PMID: 25947402 PMCID: PMC4831546 DOI: 10.4103/0366-6999.156114] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background: Recent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model. Methods: Forty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed. Results: In the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F(1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58). Conclusions: Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.
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Affiliation(s)
| | | | | | | | - Jian-Guo Zhang
- Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University; Beijing Key Laboratory of Neurostimulation; Stereotactic and Functional Neurosurgery Laboratory, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China
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Poletti S, Mazza E, Bollettini I, Locatelli C, Cavallaro R, Smeraldi E, Benedetti F. Adverse childhood experiences influence white matter microstructure in patients with schizophrenia. Psychiatry Res 2015; 234:35-43. [PMID: 26341951 DOI: 10.1016/j.pscychresns.2015.08.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 07/15/2015] [Accepted: 08/13/2015] [Indexed: 12/18/2022]
Abstract
Integrity of brain white matter (WM) tracts in adulthood could be detrimentally affected by exposure to adverse childhood experiences (ACE). Changes of diffusion tensor imaging (DTI) measures suggesting WM disruption have been reported in patients with schizophrenia together with a history of childhood maltreatment. We therefore hypothesized that ACE could be associated with altered DTI measures of WM integrity in patients with schizophrenia. We tested this hypothesis in 83 schizophrenia patients using whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial, and mean diffusivity (MD), and fractional anisotropy (FA). We observed an inverse correlation between severity of ACE and DTI measures of FA, and a positive correlation with MD in several WM tracts including corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus. Lower FA and higher MD are indexes of a reduction in fibre coherence and integrity. The association of ACE to reduced FA and increased MD in key WM tracts contributing to the functional integrity of the brain suggests that ACE might contribute to the pathophysiology of schizophrenia through a detrimental action on structural connectivity in critical cortico-limbic networks.
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Affiliation(s)
- Sara Poletti
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy.
| | - Elena Mazza
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy
| | - Irene Bollettini
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy
| | - Clara Locatelli
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy
| | - Roberto Cavallaro
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy
| | - Enrico Smeraldi
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy
| | - Francesco Benedetti
- Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele, Milan, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), University Vita-Salute San Raffaele, Milan, Italy
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Wang J, Yang N, Liao W, Zhang H, Yan CG, Zang YF, Zuo XN. Dorsal anterior cingulate cortex in typically developing children: Laterality analysis. Dev Cogn Neurosci 2015; 15:117-29. [PMID: 26602957 PMCID: PMC6989820 DOI: 10.1016/j.dcn.2015.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 10/03/2015] [Accepted: 10/05/2015] [Indexed: 12/13/2022] Open
Abstract
We aimed to elucidate the dACC laterality in typically developing children and their sex/age-related differences with a sample of 84 right-handed children (6-16 years, 42 boys). We first replicated the previous finding observed in adults that gray matter density asymmetry in the dACC was region-specific: leftward (left > right) in its superior part, rightward (left < right) in its inferior part. Intrinsic connectivity analysis of these regions further revealed region-specific asymmetric connectivity profiles in dACC as well as their sex and age differences. Specifically, the superior dACC connectivity with frontoparietal network and the inferior dACC connectivity with visual network are rightward. The superior dACC connectivity with the default network (lateral temporal cortex) was more involved in the left hemisphere. In contrast, the inferior dACC connectivity with the default network (anterior medial prefrontal cortex) was more lateralized towards the right hemisphere. The superior dACC connectivity with lateral visual cortex was more distinct across two hemispheres in girls than that in boys. This connection in boys changed with age from right-prominent to left-prominent asymmetry whereas girls developed the connection from left-prominent to no asymmetry. These findings not only highlight the complexity and laterality of the dACC but also provided insights into dynamical structure-function relationships during the development.
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Affiliation(s)
- Jue Wang
- Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ning Yang
- Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Laboratory for Functional Connectome and Development, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
| | - Wei Liao
- Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Han Zhang
- Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Chao-Gan Yan
- Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
| | - Yu-Feng Zang
- Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Xi-Nian Zuo
- Key Laboratory of Behavioral Science and Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
- Laboratory for Functional Connectome and Development, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
- Faculty of Psychology, Southwest University, Chongqing 400715, China
- Department of Psychology, School of Education Science, Guangxi Teachers Education University, Guangxi 530001, China
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Mueller BA, Lim KO, Hemmy L, Camchong J. Diffusion MRI and its Role in Neuropsychology. Neuropsychol Rev 2015; 25:250-71. [PMID: 26255305 PMCID: PMC4807614 DOI: 10.1007/s11065-015-9291-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 07/21/2015] [Indexed: 12/13/2022]
Abstract
Diffusion Magnetic Resonance Imaging (dMRI) is a popular method used by neuroscientists to uncover unique information about the structural connections within the brain. dMRI is a non-invasive imaging methodology in which image contrast is based on the diffusion of water molecules in tissue. While applicable to many tissues in the body, this review focuses exclusively on the use of dMRI to examine white matter in the brain. In this review, we begin with a definition of diffusion and how diffusion is measured with MRI. Next we introduce the diffusion tensor model, the predominant model used in dMRI. We then describe acquisition issues related to acquisition parameters and scanner hardware and software. Sources of artifacts are then discussed, followed by a brief review of analysis approaches. We provide an overview of the limitations of the traditional diffusion tensor model, and highlight several more sophisticated non-tensor models that better describe the complex architecture of the brain's white matter. We then touch on reliability and validity issues of diffusion measurements. Finally, we describe examples of ways in which dMRI has been applied to studies of brain disorders and how identified alterations relate to symptomatology and cognition.
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Situ W, Liao H, Zhou B, Xia X, Tan C. Application of diffusion tensor imaging for detecting structural changes in the brain of schizophrenic patients. Int J Psychiatry Clin Pract 2015; 19:114-8. [PMID: 25410157 DOI: 10.3109/13651501.2014.988270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE Schizophrenia is a severe psychiatric illness. Although magnetic resonance imaging has been widely used for detecting brain structural and functional abnormalities in patients with schizophrenia, the findings are highly inconsistent between reports. This study investigates structural changes in the brains of schizophrenic patients. METHODS The brains of fifty male adults with schizophrenia and fifty age- and gender-matched healthy controls were scanned by diffusion tensor imaging. The differences in fractional anisotropy (FA) values between schizophrenic patients and healthy controls were analyzed. RESULTS Schizophrenic patients exhibited significantly decreased FA values in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, left sub-temporal gyrus, left middle temporal gyrus, left cingulate gyrus, and left precentral gyrus compared with the control group. We did not find any brain regions with higher FA values in the patient group than in the control group. CONCLUSION This study suggested that structural abnormalities in the frontal region of gray matter and white matter are present at the same time in patients with schizophrenia.
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Affiliation(s)
- Weijun Situ
- Department of Radiology, Second Xiangya Hospital, Central South University , Changsha , P. R. China
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Zhou Y, Fan L, Qiu C, Jiang T. Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia. Neurosci Bull 2015; 31:207-19. [PMID: 25761914 DOI: 10.1007/s12264-014-1502-8] [Citation(s) in RCA: 133] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 11/20/2014] [Indexed: 12/15/2022] Open
Abstract
Schizophrenia is hypothesized to arise from disrupted brain connectivity. This "dysconnectivity hypothesis" has generated interest in discovering whether there is anatomical and functional dysconnectivity between the prefrontal cortex (PFC) and other brain regions, and how this dysconnectivity is linked to the impaired cognitive functions and aberrant behaviors of schizophrenia. Critical advances in neuroimaging technologies, including diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), make it possible to explore these issues. DTI affords the possibility to explore anatomical connectivity in the human brain in vivo and fMRI can be used to make inferences about functional connections between brain regions. In this review, we present major advances in the understanding of PFC anatomical and functional dysconnectivity and their implications in schizophrenia. We then briefly discuss future prospects that need to be explored in order to move beyond simple mapping of connectivity changes to elucidate the neuronal mechanisms underlying schizophrenia.
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Affiliation(s)
- Yuan Zhou
- Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China
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Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis. Schizophr Res 2015; 162:14-21. [PMID: 25620120 PMCID: PMC4339463 DOI: 10.1016/j.schres.2015.01.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 01/09/2015] [Accepted: 01/12/2015] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications. OBJECTIVE To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA). METHODS Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA. RESULTS DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls. DISCUSSION Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.
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Canu E, Agosta F, Filippi M. A selective review of structural connectivity abnormalities of schizophrenic patients at different stages of the disease. Schizophr Res 2015; 161:19-28. [PMID: 24893909 DOI: 10.1016/j.schres.2014.05.020] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 05/02/2014] [Accepted: 05/09/2014] [Indexed: 12/22/2022]
Abstract
Schizophrenia has long been hypothesized to result from a disconnection syndrome due to a disruption of the association fibers of the brain. However, only with the advent of in vivo neuroimaging, a formal disconnectivity hypothesis for schizophrenia has been developed. Diffusion tensor MRI, a non-invasive technique which is sensitive to features of tissue microstructure and to the anatomy of the white matter fibers, has gained a crucial role in the field. Here, we provide a state-of-the-art review of structural connectivity abnormalities detected in schizophrenia and discuss the most relevant findings at preclinical, first episode drug-naïve, and chronic stages. Imaging studies showed white matter alterations from the preclinical to the chronic stage of the disease, which involve the corticospinal tracts, interhemispheric connections, long association white matter tracts, cerebello-thalamo-cortical circuit, and limbic system. Such abnormalities were found to be associated with the psychiatric and cognitive manifestations of the disease and to predict, at least partially, the patient clinical evolution and response to treatment.
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Affiliation(s)
- Elisa Canu
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Agosta
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Filippi
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
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Lener MS, Wong E, Tang CY, Byne W, Goldstein KE, Blair NJ, Haznedar MM, New AS, Chemerinski E, Chu KW, Rimsky LS, Siever LJ, Koenigsberg HW, Hazlett EA. White matter abnormalities in schizophrenia and schizotypal personality disorder. Schizophr Bull 2015; 41:300-10. [PMID: 24962608 PMCID: PMC4266294 DOI: 10.1093/schbul/sbu093] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis.
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Affiliation(s)
- Marc S. Lener
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Edmund Wong
- Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Cheuk Y. Tang
- Translational and Molecular Imaging Institute, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - William Byne
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Mental Illness Research, Education, and Clinical Center (MIRECC VISN 3), James J. Peters Veterans Affairs Medical Center, Bronx, NY;,Department of Outpatient Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Kim E. Goldstein
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Nicholas J. Blair
- Mental Illness Research, Education, and Clinical Center (MIRECC VISN 3), James J. Peters Veterans Affairs Medical Center, Bronx, NY;,Research and Development, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - M. Mehmet Haznedar
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Department of Outpatient Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Antonia S. New
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Mental Illness Research, Education, and Clinical Center (MIRECC VISN 3), James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Eran Chemerinski
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Department of Outpatient Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - King-Wai Chu
- Mental Illness Research, Education, and Clinical Center (MIRECC VISN 3), James J. Peters Veterans Affairs Medical Center, Bronx, NY;,Research and Development, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Liza S. Rimsky
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Larry J. Siever
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Mental Illness Research, Education, and Clinical Center (MIRECC VISN 3), James J. Peters Veterans Affairs Medical Center, Bronx, NY;,Department of Outpatient Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Harold W. Koenigsberg
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Department of Outpatient Psychiatry, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Erin A. Hazlett
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY;,Mental Illness Research, Education, and Clinical Center (MIRECC VISN 3), James J. Peters Veterans Affairs Medical Center, Bronx, NY;,Research and Development, James J. Peters Veterans Affairs Medical Center, Bronx, NY,*To whom correspondence should be addressed; Mental Illness Research, Education, and Clinical Center, James J. Peters VA Medical Center, 130 West Kingsbridge Road, Room 6A-44, Bronx, NY, US; tel: 718-584-9000 x3701, fax: 718-364-3576, e-mail:
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Ribolsi M, Daskalakis ZJ, Siracusano A, Koch G. Abnormal asymmetry of brain connectivity in schizophrenia. Front Hum Neurosci 2014; 8:1010. [PMID: 25566030 PMCID: PMC4273663 DOI: 10.3389/fnhum.2014.01010] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 11/26/2014] [Indexed: 01/09/2023] Open
Abstract
Recently, a growing body of data has revealed that beyond a dysfunction of connectivity among different brain areas in schizophrenia patients (SCZ), there is also an abnormal asymmetry of functional connectivity compared with healthy subjects. The loss of the cerebral torque and the abnormalities of gyrification, with an increased or more complex cortical folding in the right hemisphere may provide an anatomical basis for such aberrant connectivity in SCZ. Furthermore, diffusion tensor imaging studies have shown a significant reduction of leftward asymmetry in some key white-matter tracts in SCZ. In this paper, we review the studies that investigated both structural brain asymmetry and asymmetry of functional connectivity in healthy subjects and SCZ. From an analysis of the existing literature on this topic, we can hypothesize an overall generally attenuated asymmetry of functional connectivity in SCZ compared to healthy controls. Such attenuated asymmetry increases with the duration of the disease and correlates with psychotic symptoms. Finally, we hypothesize that structural deficits across the corpus callosum may contribute to the abnormal asymmetry of intra-hemispheric connectivity in schizophrenia.
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Affiliation(s)
- Michele Ribolsi
- Dipartimento di Medicina dei Sistemi, Clinica Psichiatrica, Università di Roma Tor Vergata , Rome , Italy ; Laboratorio di Neurologia Clinica e Comportamentale, Fondazione Santa Lucia IRCCS , Rome , Italy
| | - Zafiris J Daskalakis
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto , Toronto, ON , Canada
| | - Alberto Siracusano
- Dipartimento di Medicina dei Sistemi, Clinica Psichiatrica, Università di Roma Tor Vergata , Rome , Italy
| | - Giacomo Koch
- Laboratorio di Neurologia Clinica e Comportamentale, Fondazione Santa Lucia IRCCS , Rome , Italy
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Hayakawa YK, Kirino E, Shimoji K, Kamagata K, Hori M, Ito K, Kunimatsu A, Abe O, Ohtomo K, Aoki S. Anterior cingulate abnormality as a neural correlate of mismatch negativity in schizophrenia. Neuropsychobiology 2014; 68:197-204. [PMID: 24192500 DOI: 10.1159/000355296] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Accepted: 08/26/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND Limbic circuitry, especially the anterior cingulate gyrus, has been implicated in the pathophysiology and cognitive changes of schizophrenia. Previous diffusion tensor imaging studies have demonstrated that the integrity of the anterior cingulum (AC) is abnormal in schizophrenia. However, the relationship between the abnormal AC tract integrity and the pathophysiology of schizophrenia has not been fully studied. METHODS We performed a voxelwise group comparison of white matter fractional anisotropy (FA) by using tract-based spatial statistics in 9 patients with schizophrenia and 9 matched controls. We then measured FA specifically in the AC by using a tract-specific measurement. The latency and amplitude of the mismatch negativity (MMN) were also evaluated in all subjects. RESULTS In patients with schizophrenia, tract-based spatial statistics showed a reduction in FA in broad white matter areas, including the bilateral AC, compared with controls. Tract-specific measurements confirmed the specific reduction of FA in the region of the bilateral AC. The decreased FA in the AC was correlated with prolonged MMN latency in the patient group. CONCLUSION Our study of AC structure and electrophysiological changes in schizophrenia suggest that the disruption of limbic-cortical structural networks may be part of the neural basis underlying the changes in MMN in schizophrenia.
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Affiliation(s)
- Yayoi K Hayakawa
- Department of Radiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Japan
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Wheeler AL, Voineskos AN. A review of structural neuroimaging in schizophrenia: from connectivity to connectomics. Front Hum Neurosci 2014; 8:653. [PMID: 25202257 PMCID: PMC4142355 DOI: 10.3389/fnhum.2014.00653] [Citation(s) in RCA: 172] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2014] [Accepted: 08/05/2014] [Indexed: 11/13/2022] Open
Abstract
In patients with schizophrenia neuroimaging studies have revealed global differences with some brain regions showing focal abnormalities. Examining neurocircuitry, diffusion-weighted imaging studies have identified altered structural integrity of white matter in frontal and temporal brain regions and tracts such as the cingulum bundles, uncinate fasciculi, internal capsules and corpus callosum associated with the illness. Furthermore, structural co-variance analyses have revealed altered structural relationships among regional morphology in the thalamus, frontal, temporal and parietal cortices in schizophrenia patients. The distributed nature of these abnormalities in schizophrenia suggests that multiple brain circuits are impaired, a neural feature that may be better addressed with network level analyses. However, even with the advent of these newer analyses, a large amount of variability in findings remains, likely partially due to the considerable heterogeneity present in this disorder.
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Affiliation(s)
- Anne L Wheeler
- Kimel Family Translational Imaging Genetics Laboratory, Centre for Addiction and Mental Health, Research Imaging Centre Toronto, ON, Canada ; Department of Psychiatry, University of Toronto Toronto, ON, Canada
| | - Aristotle N Voineskos
- Kimel Family Translational Imaging Genetics Laboratory, Centre for Addiction and Mental Health, Research Imaging Centre Toronto, ON, Canada ; Department of Psychiatry, University of Toronto Toronto, ON, Canada
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