Journal of Neurology, Neurosurgery, and Psychiatry
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Frontomedian cortex is central for moral deficits in behavioral variant frontotemporal dementia
Journal:
Manuscript ID: Article Type:
Complete List of Authors:
jnnp-2014-308387.R1 Letter (original) n/a
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Date Submitted by the Author:
Journal of Neurology, Neurosurgery, and Psychiatry
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Schroeter, Matthias; Max Planck Institute for Human Cognitive and Brain Sciences, Neurology Bzdok, Danilo; Institute for Neuroscience and Medicine (INM-1), Research Center Jülich, Eickhoff, Simon; Institute for Clinical Neuroscience and Medical Psychology, HHU Düsseldorf, Neumann, Jane; Max Planck Institute for Human Cognitive and Brain Sciences, Neurology DEMENTIA, NEUROPSYCHIATRY, NEUROPSYCHOLOGY, PET, MRI Neuropsychiatry
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Specialty:
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Keywords:
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Letter for JNNP
Frontomedian cortex is central for moral deficits in behavioral
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variant frontotemporal dementia
Matthias L. Schroeter, MD, PhDa,b,c; Danilo Bzdok, MDd; Simon B. Eickhoff, MD, PhDd,e;
a
Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig; b
c
Day Clinic of Cognitive Neurology, University of Leipzig, 04103 Leipzig;
LIFE - Leipzig Research Center for Civilization Diseases, University of Leipzig; d
e f
& Jane Neumann, PhDa,f
Institute for Neuroscience and Medicine (INM-1), Research Center Jülich;
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Institute for Clinical Neuroscience and Medical Psychology, HHU Düsseldorf;
Integrated Research and Treatment Center Adiposity Diseases, Leipzig University Hospital; Germany
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Word count title/text: 12/994
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Number of references: 5 Running title: Moral dysfunction in bvFTD
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Statistical analysis: Jane Neumann Study funding: MLS Parkinson’s Disease Foundation, LIFE – Leipzig Research Center for Civilization Diseases at the University of Leipzig, MaxNetAging. MLS & JN German Federal Ministry of Education
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and Research. JN & SE German Research Foundation. DB German National Academic Foundation. SBE NIH, Helmholtz Initiative on Systems Biology, European EFT program.
Corresponding author: Matthias L. Schroeter, MD, PhD, MA
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Max Planck Institute for Human Cognitive and Brain Sciences Stephanstr. 1A, 04103 Leipzig
email:
[email protected] phone: ++49-341-97 24 962 fax:
++49-341-97 24 989
http://mc.manuscriptcentral.com/jnnp
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Germany
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Journal of Neurology, Neurosurgery, and Psychiatry
Journal of Neurology, Neurosurgery, and Psychiatry M. L. Schroeter et al.
Moral dysfunction in bvFTD
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Authors’ contributions to manuscript •
Matthias L. Schroeter planned the design/conceptualization of the study, analyzed and interpreted the data, and drafted and revised the manuscript.
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Danilo Bzdok contributed to the design/conceptualization of the study, interpreted the
data, and revised the manuscript.
•
Simon B. Eickhoff contributed to the design/conceptualization of the study, interpreted
the data, and revised the manuscript.
•
Jane Neumann planned the design/conceptualization of the study, analyzed and
interpreted the data, and revised the manuscript.
Disclosure statement
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•
Matthias L. Schroeter reports no disclosures.
•
Danilo Bzdok reports no disclosures.
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Simon B. Eickhoff reports no disclosures.
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Jane Neumann reports no disclosures.
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Journal of Neurology, Neurosurgery, and Psychiatry M. L. Schroeter et al.
Recently,
Moral dysfunction in bvFTD
neurodegenerative
diseases
have
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increasingly
been
conceptualized
as
‘nexopathies’ or disconnection syndromes, in which connectivity changes in neural networks represent the most relevant and characteristic features.1 One of these diseases, behavioral
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variant frontotemporal dementia (bvFTD), is characterized by morally deviant actions as an early clinical hallmark of this disease, beside other specific changes in personality and behavior.2,3 Elucidating the neural correlates of these moral impairments contributes to the understanding of this in young subjects frequent dementia syndrome and of moral actions
per se.
One approach towards understanding moral impairments in bvFTD is comparing affected neural networks in bvFTD with brain networks involved in moral processing in healthy subjects during functional imaging studies. Remarkably, this approach enables extracting
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new concepts of diseases by using two independent cohorts and imaging methods (lesion
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studies in disease cohorts vs. functional imaging studies in healthy subjects).3 Because
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numerous imaging studies have been published on these issues to date, quantitative metaanalytic approaches are possible.
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Accordingly, we combine here two comprehensive quantitative meta-analyses of anatomical and functional neuroimaging data by means of the well established likelihood estimate
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method to provide evidence for alterations of regions involved in moral reasoning in bvFTD. Likelihood estimate meta-analyses are based on coordinates of peaks for atrophy or
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hypometabolism during rest in patients if compared with control subjects, or coordinates from functional imaging studies, where healthy subjects are stimulated with psychological stimuli. The statistical analysis determines brain regions that exhibit a higher convergence of these
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peaks across independent studies than would arise by chance. The final likelihood estimate map extracts the prototypical neural correlates of a specific disease or a prototypical network
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of brain regions that is associated with a specific cognitive paradigm (see for detailed information on methods3,4).
We used results from our recent meta-analysis3 identifying regions that are consistently affected by bvFTD in terms of atrophy (magnetic resonance imaging, MRI) or
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Journal of Neurology, Neurosurgery, and Psychiatry M. L. Schroeter et al.
Moral dysfunction in bvFTD
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hypometabolism during rest (18F-fluorodeoxyglucose positron emission tomography, FDGPET). This analysis incorporated 9 MRI studies and 11 FDG-PET studies including a total of 417 patients with bvFTD (MRI 185/FDG-PET 232) and 406 control subjects. To investigate
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whether these brain regions converge with those reliably implicated in moral processing, we quantitatively compared this data, using a minimum statistic conjunction analysis, with a recent comprehensive meta-analysis across functional activation imaging studies that investigated moral cognition in healthy subjects applying the same meta-analytic approach.4 The latter study incorporated 67 neuroimaging experiments reporting 507 activation foci.
[Figure 1]
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Using this large-scale approach towards the robust definition of pathology and function, we
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identified four regions in the anterior frontomedian and paracingulate cortex, in Brodmann
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areas 9, 10 and 32, exhibiting not only atrophy in bvFTD but also consistent activation increases during moral cognition tasks in healthy subjects (Figure 1). These brain regions
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are known to be central hubs for moral reasoning.2 In detail, atrophic brain regions in bvFTD included a total of 1735 voxels, activation in moral cognition was observed in a neural
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network spreading across 3203 voxels in healthy subjects. These clusters overlapped specifically in 113 voxels, where one voxel generally corresponds to a volume of 2 x 2 x 2
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mm. The quantitative analysis showed a relative overlap in 6.51 % of all atrophic brain regions in bvFTD, and in 3.53 % of the whole moral cognition network.
Though small, this regional overlap/conjunction is statistically significant at p
