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      Network structure of brain atrophy in de novo Parkinson's disease

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

          DOI: http://dx.doi.org/10.7554/eLife.08440.001

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          Although Parkinson's disease is the second most common neurodegenerative disorder, its cause is not known and there is no cure. The symptoms of Parkinson's disease, which include tremor and slowing of voluntary movements, get progressively worse over time. The numbers of neurons in certain brain regions also decrease, causing those parts of the brain to shrink; this is known as ‘atrophy’. However, no conclusive signs of atrophy have been found in the brains of people in the early stages of the disease.

          One theory suggests that Parkinson's disease is caused by a toxic protein that is able to spread from neuron to neuron. Recent advances in brain imaging have made it possible to map networks in the living human brain—the so-called brain connectome. These networks could form the ‘highways’ through which a disease-causing agent might spread.

          The Parkinson's Progression Markers Initiative (PPMI) is a large study that collects data from hundreds of people in an effort to identify the causes of Parkinson's disease. Zeighami et al. have now analyzed MRI scans that were collected as part of this initiative, which show the structure of the brains of 230 people in the early stages of Parkinson's disease. Comparing these scans to those from age-matched healthy individuals allowed Zeighami et al. to identify the set of brain regions that show atrophy in the early stages of Parkinson's disease. These regions correspond to a normal brain network, and the relative extent of atrophy in each brain region supports the theory that the disease spreads through the connectome.

          The patients who were enrolled in this study will continue to be evaluated on a yearly basis. Zeighami et al. plan to continue mapping how the disease progresses throughout the brain and to relate this to the development of new symptoms of Parkinson's disease.

          DOI: http://dx.doi.org/10.7554/eLife.08440.002

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          Most cited references37

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          Stages in the development of Parkinson's disease-related pathology.

          The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1-2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3-4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5-6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.
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            The debate over dopamine's role in reward: the case for incentive salience.

            Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking', learning, and 'wanting'. Does dopamine mostly mediate the hedonic impact of reward ('liking')? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli ('wanting')? Each hypothesis is evaluated here, and it is suggested that the incentive salience or 'wanting' hypothesis of dopamine function may be consistent with more evidence than either learning or 'liking'. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic 'liking' for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal 'wanting', and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive 'wanting' in addiction, but also provides opportunities for experiments to disentangle 'wanting', 'liking', and learning hypotheses. Results from studies that exploited those opportunities are described here. In short, dopamine's contribution appears to be chiefly to cause 'wanting' for hedonic rewards, more than 'liking' or learning for those rewards.
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              Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space

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                Author and article information

                Contributors
                Role: Reviewing editor
                Journal
                eLife
                eLife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                2050-084X
                07 September 2015
                2015
                : 4
                : e08440
                Affiliations
                [1 ]deptMcConnell Brain Imaging Centre, Montreal Neurological Institute , McGill University , Montreal, Canada
                [2 ]deptService de Neurologie A , CHU Clermont-Ferrand , Clermont-Ferrand, France
                Washington University in St Louis , United States
                Washington University in St Louis , United States
                Author notes
                [* ]For correspondence: alain.dagher@ 123456mcgill.ca
                Article
                08440
                10.7554/eLife.08440
                4596689
                26344547
                98d7b56e-8f06-4d99-aa16-042721ed66a5
                © 2015, Zeighami et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 30 April 2015
                : 05 September 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000864, Michael J. Fox Foundation for Parkinson's Research (MJFF);
                Award ID: 320897
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000243, W. Garfield Weston Foundation;
                Award ID: 320897
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000957, Alzheimer's Association;
                Award ID: 320897
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research (Instituts de recherche en santé du Canada);
                Award ID: MOP-136776
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000038, Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada);
                Award ID: 436259-13
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                2.3
                The pattern of atrophy in Parkinson's disease is consistent with the disease spreading via intrinsic brain networks.

                Life sciences
                mri,substantia nigra,basal ganglia,independent component analysis,deformation-based morphometry,human

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