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Journal Article•DOI•

Altered Functional and Anatomical Connectivity in Schizophrenia

Jazmin Camchong1, Angus W. MacDonald1, Christopher J. Bell1, Bryon A. Mueller1, Kelvin O. Lim1 •
University of Minnesota1
01 May 2011-Schizophrenia Bulletin (Oxford University Press)-Vol. 37, Iss: 3, pp 640-650
TL;DR: Convergent fMRI and DTI findings that are consistent with the disconnection hypothesis in schizophrenia, particularly in medial frontal regions, while adding some insight of the relationship between brain disconnectivity and behavior are shown.
Abstract: Background: Schizophrenia is characterized by a lack of integration between thought, emotion, and behavior. A disruption in the connectivity between brain processes may underlie this schism. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were used to evaluate functional and anatomical brain connectivity in schizophrenia. Methods: In all, 29 chronic schizophrenia patients (11 females, age: mean = 41.3, SD = 9.28) and 29 controls (11 females, age: mean = 41.1, SD = 10.6) were recruited. Schizophrenia patients were assessed for severity of negative and positive symptoms and general cognitive abilities of attention/concentration and memory. Participants underwent a resting-fMRI scan and a DTI scan. For fMRI data, a hybrid independent components analysis was used to extract the group default mode network (DMN) and accompanying time-courses. Voxel-wise whole-brain multiple regressions with corresponding DMN time-courses was conducted for each subject. A t-test was conducted on resulting DMN correlation maps to look between-group differences. For DTI data, voxel-wise statistical analysis of the fractional anisotropy data was carried out to look for between-group differences. Voxel-wise correlations were conducted to investigate the relationship between brain connectivity and behavioral measures. Results: Results revealed altered functional and anatomical connectivity in medial frontal and anterior cingulate gyri of schizophrenia patients. In addition, frontal connectivity in schizophrenia patients was positively associated with symptoms as well as with general cognitive ability measures. Discussion: The present study shows convergent fMRI and DTI findings that are consistent with the disconnection hypothesis in schizophrenia, particularly in medial frontal regions, while adding some insight of the relationship between brain disconnectivity and behavior.
Citations
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Journal Article•DOI•
Large-scale brain networks and psychopathology: a unifying triple network model

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Vinod Menon
01 Oct 2011-Trends in Cognitive Sciences
TL;DR: A triple network model of aberrant saliency mapping and cognitive dysfunction in psychopathology is proposed, emphasizing the surprising parallels that are beginning to emerge across psychiatric and neurological disorders.

2,712 citations

Journal Article•DOI•
Default Mode Network Activity and Connectivity in Psychopathology

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Susan Whitfield-Gabrieli1, Judith M. Ford2•
Massachusetts Institute of Technology1, University of California, San Francisco2
29 Mar 2012-Annual Review of Clinical Psychology
TL;DR: Functional magnetic resonance imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of theDMN isassociated with better performance on attention-demanding tasks.
Abstract: Neuropsychiatric disorders are associated with abnormal function of the default mode network (DMN), a distributed network of brain regions more active during rest than during performance of many attention-demanding tasks and characterized by a high degree of functional connectivity (i.e., temporal correlations between brain regions). Functional magnetic resonance imaging studies have revealed that the DMN in the healthy brain is associated with stimulus-independent thought and self-reflection and that greater suppression of the DMN is associated with better performance on attention-demanding tasks. In schizophrenia and depression, the DMN is often found to be hyperactivated and hyperconnected. In schizophrenia this may relate to overly intensive self-reference and impairments in attention and working memory. In depression, DMN hyperactivity may be related to negative rumination. These findings are considered in terms of what is known about psychological functions supported by the DMN, and alteration of the DMN in other neuropsychiatric disorders.

1,137 citations

Journal Article•DOI•
Aberrant Frontal and Temporal Complex Network Structure in Schizophrenia: A Graph Theoretical Analysis

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Martijn P. van den Heuvel1, René C.W. Mandl1, Cornelis J. Stam, René S. Kahn2, Hilleke E. Hulshoff Pol1 •
Utrecht University1, VU University Amsterdam2
24 Nov 2010-The Journal of Neuroscience
TL;DR: It is demonstrated that schizophrenia involves an aberrant topology of the structural infrastructure of the brain network, which suggests that schizophrenia patients have a less strongly globally integrated structural brain network with a reduced central role for key frontal hubs.
Abstract: Brain regions are not independent. They are interconnected by white matter tracts, together forming one integrative complex network. The topology of this network is crucial for efficient information integration between brain regions. Here, we demonstrate that schizophrenia involves an aberrant topology of the structural infrastructure of the brain network. Using graph theoretical analysis, complex structural brain networks of 40 schizophrenia patients and 40 human healthy controls were examined. Diffusion tensor imaging was used to reconstruct the white matter connections of the brain network, with the strength of the connections defined as the level of myelination of the tracts as measured through means of magnetization transfer ratio magnetic resonance imaging. Patients displayed a preserved overall small-world network organization, but focusing on specific brain regions and their capacity to communicate with other regions of the brain revealed significantly longer node-specific path lengths (higher L) of frontal and temporal regions, especially of bilateral inferior/superior frontal cortex and temporal pole regions. These findings suggest that schizophrenia impacts global network connectivity of frontal and temporal brain regions. Furthermore, frontal hubs of patients showed a significant reduction of betweenness centrality, suggesting a less central hub role of these regions in the overall network structure. Together, our findings suggest that schizophrenia patients have a less strongly globally integrated structural brain network with a reduced central role for key frontal hubs, resulting in a limited structural capacity to integrate information across brain regions.

625 citations

Cites background from "Altered Functional and Anatomical C..."

  • ...…Van den Heuvel et al., 2008b, 2009; Greicius et al., 2009; Honey et al., 2009, 2010). and recent studies have suggested both aberrant functional as well as diminished structural connectivity of specific frontal and hippocampal regions in schizophrenia (Zhou et al., 2008; Camchong et al., 2009)....

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Journal Article•DOI•
Dysconnectivity in schizophrenia: where are we now?

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William Pettersson-Yeo1, Paul Allen1, Stefania Benetti1, Philip McGuire1, Andrea Mechelli1 •
King's College London1
01 Apr 2011-Neuroscience & Biobehavioral Reviews
TL;DR: The main trends to emerge are that schizophrenia is associated with connectivity reductions, as opposed to increases, relative to healthy controls, and that this is particularly evident in the connections involving the frontal lobe.

613 citations

Journal Article•DOI•
Disrupted Axonal Fiber Connectivity in Schizophrenia

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Andrew Zalesky1, Alex Fornito2, Alex Fornito1, Marc L. Seal1, Luca Cocchi1, Carl-Fredrik Westin3, Edward T. Bullmore2, Gary F. Egan1, Christos Pantelis1 •
University of Melbourne1, University of Cambridge2, Brigham and Women's Hospital3
01 Jan 2011-Biological Psychiatry
TL;DR: Evidence of widespread dysconnectivity in white-matter connectional architecture in a large sample of patients with schizophrenia is presented, pointing to a multifaceted pathophysiology in schizophrenia encompassing axonal as well as putative synaptic mechanisms.

433 citations

References
More filters
Journal Article•DOI•
Advances in functional and structural MR image analysis and implementation as FSL.

[...]

Stephen M. Smith1, Mark Jenkinson1, Mark W. Woolrich1, Mark W. Woolrich2, Christian F. Beckmann1, Behrens Tej.1, Heidi Johansen-Berg1, Peter R. Bannister1, M De Luca1, Ivana Drobnjak1, D E Flitney1, Rami K. Niazy1, J Saunders1, J Vickers1, Yongyue Zhang1, N. De Stefano2, J M Brady3, Paul M. Matthews1 •
John Radcliffe Hospital1, University of Siena2, University of Oxford3
01 Jan 2004-NeuroImage
TL;DR: A review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB) on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data.

12,097 citations

"Altered Functional and Anatomical C..." refers methods in this paper

  • ...To compare functional connectivitybetweengroups,weusedawhole-brainapproach tocreatestatisticalparametricmapsofthetstatistics(using FSL).(44) These unpaired t statistics tested, at each voxel in thebrain, fordifferences incouplingwiththedefaultmode, as indexedbyDMNcorrelationcoefficients....

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  • ...Voxelwise statistics were conducted with Randomise from FSL.44 Randomise is a permutation program that enables modeling and inference using cluster-based thresholding and was used to test for between-group differences in FA....

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  • ...Voxelwise statistics were conducted with Randomise from FSL.(44) Randomise is a permutation program that enables modeling and inference using cluster-based thresholding and was used to test for between-group differences in FA....

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Journal Article•DOI•
A default mode of brain function.

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Marcus E. Raichle1, Ann Mary MacLeod1, Abraham Z. Snyder1, William J. Powers, Debra A. Gusnard1, Gordon L. Shulman1 •
Washington University in St. Louis1
16 Jan 2001-Proceedings of the National Academy of Sciences of the United States of America
TL;DR: A baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF is identified, suggesting the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
Abstract: A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.

10,708 citations

"Altered Functional and Anatomical C..." refers methods or result in this paper

  • ...One prominent network is formally similar to the DMN originally identified by Raichle et al.5 fMRI data previously collected to investigate functional connectivity of the DMN in schizophrenia patients have been examined using 2 approaches....

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  • ...FMRI data confirmed the existence of a fronto-parietaloccipital network in schizophrenia, and healthy controls comprisedofbrain regions that havepreviously shownsynchronized intrinsic fluctuations during rest known as the DMN.5,43,52 Consistent with a previous study that used ICA to examine resting state networks in schizophrenia patients,8 groups did not differ in their representation within the chosen DMN network extracted from ICA....

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  • ...It has been reported that in healthy controls, decreased regulation of internal thoughts (manifested as reports of increased mind wandering) is associated with increased activation in the DMN.59 This concept can be applicable to present findings in that schizophrenia patients that had exaggerated disorganized internal thoughts (manifested as more severe schizophrenia-like symptoms such as hallucinations and delusions) show increased engagement of the DMN....

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  • ...FMRI studies on healthy controls have found correlations between performance of a task requiring executive functioning and by guest on N ovem ber 4, 2016 http://schizophreniabulletin.oxfordjournals.org/ D ow nloaded from the strength of functional connectivity of regions within the DMN.23,24 Abnormalities in the intrinsic fluctuations of the DMN may be relevant to understanding clinical symptoms and poor cognitive performance of schizophrenia patients....

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  • ...One prominent network is formally similar to the DMN originally identified by Raichle et al.(5)...

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Journal Article•DOI•
Fast robust automated brain extraction

[...]

Stephen M. Smith1•
John Radcliffe Hospital1
01 Nov 2002-Human Brain Mapping
TL;DR: An automated method for segmenting magnetic resonance head images into brain and non‐brain has been developed and described and examples of results and the results of extensive quantitative testing against “gold‐standard” hand segmentations, and two other popular automated methods.
Abstract: An automated method for segmenting magnetic resonance head images into brain and non-brain has been developed. It is very robust and accurate and has been tested on thousands of data sets from a wide variety of scanners and taken with a wide variety of MR sequences. The method, Brain Extraction Tool (BET), uses a deformable model that evolves to fit the brain's surface by the application of a set of locally adaptive model forces. The method is very fast and requires no preregistration or other pre-processing before being applied. We describe the new method and give examples of results and the results of extensive quantitative testing against "gold-standard" hand segmentations, and two other popular automated methods.

9,887 citations

Journal Article•DOI•
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

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Stephen M. Smith1, Mark Jenkinson1, Heidi Johansen-Berg1, Daniel Rueckert2, Thomas E. Nichols3, Clare E. Mackay1, Kate E. Watkins1, Olga Ciccarelli4, M Z Cader1, Paul M. Matthews1, Timothy E.J. Behrens1 •
University of Oxford1, Imperial College London2, University of Michigan3, University College London4
15 Jul 2006-NeuroImage
TL;DR: TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies by solving the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis.

5,959 citations

Journal Article•DOI•
Cognitive and emotional influences in anterior cingulate cortex

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George Bush1, Phan Luu2, Michael I. Posner3•
Harvard University1, University of Oregon2, Cornell University3
01 Jun 2000-Trends in Cognitive Sciences
TL;DR: Various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing, and how the success of this regulation in controlling responses might be correlated with cingulate size.

5,824 citations

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