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192 Research products

  • Neuroinformatics
  • Open Access
  • National Institutes of Health
  • HEALTHY AGING AND SENILE DEMENTIA

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Armstrong, Richard A.; Cairns, Nigel J.;

    Recent research suggests cell-to-cell transfer of pathogenic proteins such as tau and α-synuclein may play a role in neurodegeneration. Pathogenic spread along neural pathways may give rise to specific spatial patterns of the neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of NCI were compared in four tauopathies, viz., Alzheimer's disease, Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, two synucleinopathies, viz., dementia with Lewy bodies and multiple system atrophy, the 'fused in sarcoma' (FUS)-immunoreactive inclusions in neuronal intermediate filament inclusion disease, and the transactive response DNA-binding protein (TDP-43)-immunoreactive inclusions in frontotemporal lobar degeneration, a TDP-43 proteinopathy (FTLD-TDP). Regardless of molecular group or morphology, NCI were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 μm, approximating to the dimension of cell columns associated with the cortico-cortical pathways. The data suggest that cortical NCI in different disorders exhibit a similar spatial pattern in the cortex consistent with pathogenic spread along anatomical pathways. Hence, treatments designed to protect the cortex from neurodegeneration may be applicable across several different disorders. © 2012 Springer-Verlag.

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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2012
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    Journal of Neural Transmission
    Article . 2012 . Peer-reviewed
    License: Springer TDM
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Europe PubMed Central
      Other literature type . 2012
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Journal of Neural Transmission
      Article . 2012 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lu, Hanna; Li, Jing; Zhang, Li; Meng, Lin; +2 Authors

    Additional file 1: Supplementary Table 1. The magnitude and distribution of SCD-dependent electric fields in PD patients and normal controls. Supplementary Table 2. The distribution of SCD-dependent electric fields in PD patients and normal controls. Supplementary Table 3. The focality of SCD-dependent electric fields in PD patients and normal controls. Supplementary Figure 1. Head models of transcranial magnetic stimulation (TMS)-induced SCD-dependent electric fields (E-fields) in early-stage PD patients. Supplementary Figure 2. Comparisons of the focality of the SCD-dependent transcranial magnetic stimulation (TMS)-induced electric fields (E-fields) in normal controls (NCs) and early-stage Parkinson?s disease (PD) patients. Supplementary Figure 3. Receiver-operator characteristic (ROC) curves for the cognition and the geometric and morphometric features with differential values in early-stage Parkinson?s disease (PD) patients.

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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ figsharearrow_drop_down
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Cavedo, Enrica; Tran, Philippe; Thoprakarn, Urielle; Martini, Jean-Baptiste; +10 Authors

    Abstract Objectives QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists. Methods Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland–Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists. Results The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes. Conclusions QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases. Key Points • QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists. • QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods. • QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ INRIA a CCSD electro...arrow_drop_down
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    European Radiology
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    European Radiology
    Article . 2022 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ INRIA a CCSD electro...arrow_drop_down
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      European Radiology
      Article . 2022 . Peer-reviewed
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    Authors: Hoyos-Idrobo, Andrés; Schwartz, Yannick; Varoquaux, Gaël; Thirion, Bertrand;

    International audience; —The identification of image regions associated with external variables through discriminative approaches yields ill-posed estimation problems. This estimation challenge can be tackled by imposing sparse solutions. However, the sensitivity of sparse estimators to correlated variables leads to non-reproducible results, and only a subset of the important variables are selected. In this paper, we explore an approach based on bagging clustering-based data compression in order to alleviate the instability of sparse models. Specifically, we design a new framework in which the estimator is built by averaging multiple models estimated after feature clustering, to improve the conditioning of the model. We show that this combination of model averaging with spatially consistent compression can have the virtuous effect of increasing the stability of the weight maps, allowing a better interpretation of the results. Finally, we demonstrate the benefit of our approach on several predictive modeling problems.

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    Other literature type . Conference object . 2015
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    https://doi.org/10.1109/prni.2...
    Conference object . 2015 . Peer-reviewed
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      Other literature type . Conference object . 2015
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      https://doi.org/10.1109/prni.2...
      Conference object . 2015 . Peer-reviewed
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    Authors: Ridgway, Gerard R.; Litvak, Vladimir; Flandin, Guillaume; Friston, Karl J.; +1 Authors

    Statistical parametric mapping (SPM) locates significant clusters based on a ratio of signal to noise (a ‘contrast’ of the parameters divided by its standard error) meaning that very low noise regions, for example outside the brain, can attain artefactually high statistical values. Similarly, the commonly applied preprocessing step of Gaussian spatial smoothing can shift the peak statistical significance away from the peak of the contrast and towards regions of lower variance. These problems have previously been identified in positron emission tomography (PET) (Reimold et al., 2006) and voxel-based morphometry (VBM) (Acosta-Cabronero et al., 2008), but can also appear in functional magnetic resonance imaging (fMRI) studies. Additionally, for source-reconstructed magneto- and electro-encephalography (M/EEG), the problems are particularly severe because sparsity-favouring priors constrain meaningfully large signal and variance to a small set of compactly supported regions within the brain. (Acosta-Cabronero et al., 2008) suggested adding noise to background voxels (the ‘haircut’), effectively increasing their noise variance, but at the cost of contaminating neighbouring regions with the added noise once smoothed. Following theory and simulations, we propose to modify – directly and solely – the noise variance estimate, and investigate this solution on real imaging data from a range of modalities. Highlights ► Statistical parametric mapping judges significance with a signal-to-noise ratio. ► Low noise, e.g. outside the brain, can yield artefactually high statistical values. ► Spatial smoothing can shift peaks substantially towards regions of low variance. ► Source-reconstructed M/EEG data exhibits the problem particularly severely. ► The problem can be addressed by modifying the noise variance estimate.

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    Europe PubMed Central
    Article . 2012
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    NeuroImage
    Article . 2012 . Peer-reviewed
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      Europe PubMed Central
      Article . 2012
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      NeuroImage
      Article . 2012 . Peer-reviewed
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    Authors: Chen, Hsiang-Han; Eteleeb, Abdallah; Wang, Ciyang; Fernandez, Maria Victoria; +18 Authors

    Additional file 5. Supplementary Fig. S4.

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    Authors: Bruno A. Benitez; Nigel J. Cairns; Robert E. Schmidt; John C. Morris; +3 Authors

    Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (AD-ANCL) is a multisystem disease caused by mutations in the DNAJC5 gene. DNAJC5 encodes Cysteine String Protein-alpha (CSPα), a putative synaptic protein. AD-ANCL has been traditionally considered a lysosomal storage disease based on the intracellular accumulation of ceroid material. Here, we report for the first time the pathological findings of a patient in a clinically early stage of disease, which exhibits the typical neuronal intracellular ceroid accumulation and incipient neuroinflammation but no signs of brain atrophy, neurodegeneration or massive synaptic loss. Interestingly, we found minimal or no apparent reductions in CSPα or synaptophysin in the neuropil. In contrast, brain homogenates from terminal AD-ANCL patients exhibit significant reductions in SNARE-complex forming presynaptic protein levels, including a significant reduction in CSPα and SNAP-25. Frozen samples for the biochemical analyses of synaptic proteins were not available for the early stage AD-ANLC patient. These results suggest that the degeneration seen in the patients with AD-ANCL reported here might be a consequence of both the early effects of CSPα mutations at the cellular soma, most likely lysosome function, and subsequent neuronal loss and synaptic dysfunction.

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    Europe PubMed Central
    Article . 2015
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    Acta Neuropathologica Communications
    Article . 2015 . Peer-reviewed
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    Acta Neuropathologica Communications
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      Europe PubMed Central
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      Acta Neuropathologica Communications
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      Acta Neuropathologica Communications
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    Authors: A, Tam; C, Laurent; S, Gauthier; C, Dansereau;

    A key issue to Alzheimer's disease clinical trial failures is poor participant selection. Participants have heterogeneous cognitive trajectories and many do not decline during trials, which reduces a study's power to detect treatment effects. Trials need enrichment strategies to enroll individuals who will decline. We developed machine learning models to predict cognitive trajectories in participants with early Alzheimer's disease (n=1342) and presymptomatic individuals (n=756) over 24 and 48 months respectively. Baseline magnetic resonance imaging, cognitive tests, demographics, and APOE genotype were used to classify decliners, measured by an increase in CDR-Sum of Boxes, and non-decliners with up to 79% area under the curve (cross-validated and out-of-sample). Using these prognostic models to recruit enriched cohorts of decliners can reduce required sample sizes by as much as 51%, while maintaining the same detection power, and thus may improve trial quality, derisk endpoint failures, and accelerate therapeutic development in Alzheimer's disease. Comment: 11 pages, 3 main figures, 3 main tables, supplementary material (3 tables, 2 figures), incorporated feedback from reviewers in the introduction and discussion

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    The Journal of Prevention of Alzheimer s Disease
    Article . 2022 . Peer-reviewed
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    https://doi.org/10.48550/arxiv...
    Article . 2021
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      The Journal of Prevention of Alzheimer s Disease
      Article . 2022 . Peer-reviewed
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      Article . 2021
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    Authors: Nelly Joseph-Mathurin; Guoqiao Wang; Kejal Kantarci; Clifford R. Jack; +54 Authors

    Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds (CMBs) and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we evaluated longitudinally families affected by dominantly inherited Alzheimer disease (DIAD). Methods: Mutation carriers (n=310) and non-carriers (n=201) underwent neuroimaging, including gradient echo MR sequences to detect CMHs, neuropsychological, and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical marker of disease. Results: Three percent of non-carriers and eight percent of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMH. APOE-e4 status was not associated with the prevalence or incidence of CMHs. Prevalent or incident CMHs predicted faster change in clinical dementia rating although not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of two or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95±10.04 per year). Conclusion: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug related CMHs.

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    Europe PubMed Central
    Article . 2021
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    Neurology
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    DZNE Pub
    Article . 2021
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    Neurology
    Article . 2021 . Peer-reviewed
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      Neurology
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      DZNE Pub
      Article . 2021
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      Neurology
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    Authors: Nima Masoumi; Hassan Rivaz; M. Omair Ahmad; Yiming Xiao;

    Purpose: Diffeomorphic image registration is essential in many medical imaging applications. Several registration algorithms of such type have been proposed, but primarily for intra-contrast alignment. Currently, efficient inter-modal/contrast diffeomorphic registration, which is vital in numerous applications, remains a challenging task. Methods: We proposed a novel inter-modal/contrast registration algorithm that leverages Robust PaTch-based cOrrelation Ratio (RaPTOR) metric to allow inter-modal/contrast image alignment and bandlimited geodesic shooting demonstrated in Fourier Approximated Lie Algebras (FLASH) algorithm for fast diffeomorphic registration. Results: The proposed algorithm, named DiffeoRaptor, was validated with three public databases for the tasks of brain and abdominal image registration while comparing the results against three state-of-the-art techniques, including FLASH, NiftyReg, and Symmetric image normalization (SyN). Conclusions: Our results demonstrated that DiffeoRaptor offered comparable or better registration performance in terms of registration accuracy. Moreover, DiffeoRaptor produces smoother deformations than SyN in inter-modal and contrast registration. The code for DiffeoRaptor is publicly available at https://github.com/nimamasoumi/DiffeoRaptor.

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    International Journal of Computer Assisted Radiology and Surgery
    Article . 2022 . Peer-reviewed
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      International Journal of Computer Assisted Radiology and Surgery
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    Authors: Armstrong, Richard A.; Cairns, Nigel J.;

    Recent research suggests cell-to-cell transfer of pathogenic proteins such as tau and α-synuclein may play a role in neurodegeneration. Pathogenic spread along neural pathways may give rise to specific spatial patterns of the neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of NCI were compared in four tauopathies, viz., Alzheimer's disease, Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, two synucleinopathies, viz., dementia with Lewy bodies and multiple system atrophy, the 'fused in sarcoma' (FUS)-immunoreactive inclusions in neuronal intermediate filament inclusion disease, and the transactive response DNA-binding protein (TDP-43)-immunoreactive inclusions in frontotemporal lobar degeneration, a TDP-43 proteinopathy (FTLD-TDP). Regardless of molecular group or morphology, NCI were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 μm, approximating to the dimension of cell columns associated with the cortico-cortical pathways. The data suggest that cortical NCI in different disorders exhibit a similar spatial pattern in the cortex consistent with pathogenic spread along anatomical pathways. Hence, treatments designed to protect the cortex from neurodegeneration may be applicable across several different disorders. © 2012 Springer-Verlag.

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    Europe PubMed Central
    Other literature type . 2012
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    Journal of Neural Transmission
    Article . 2012 . Peer-reviewed
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      Journal of Neural Transmission
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    Authors: Lu, Hanna; Li, Jing; Zhang, Li; Meng, Lin; +2 Authors

    Additional file 1: Supplementary Table 1. The magnitude and distribution of SCD-dependent electric fields in PD patients and normal controls. Supplementary Table 2. The distribution of SCD-dependent electric fields in PD patients and normal controls. Supplementary Table 3. The focality of SCD-dependent electric fields in PD patients and normal controls. Supplementary Figure 1. Head models of transcranial magnetic stimulation (TMS)-induced SCD-dependent electric fields (E-fields) in early-stage PD patients. Supplementary Figure 2. Comparisons of the focality of the SCD-dependent transcranial magnetic stimulation (TMS)-induced electric fields (E-fields) in normal controls (NCs) and early-stage Parkinson?s disease (PD) patients. Supplementary Figure 3. Receiver-operator characteristic (ROC) curves for the cognition and the geometric and morphometric features with differential values in early-stage Parkinson?s disease (PD) patients.

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