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Sample records for disease neuroimaging initiative

  1. The Alzheimer’s Disease Neuroimaging Initiative Informatics Core: A Decade in Review

    PubMed Central

    Toga, Arthur W.; Crawford, Karen L.

    2015-01-01

    The Informatics Core of the Alzheimer’s Diseases Neuroimaging Initiative (ADNI) has coordinated data integration and dissemination for a continually growing and complex dataset in which both data contributors and recipients span institutions, scientific disciplines and geographic boundaries. This article provides an update on the accomplishments and future plans. PMID:26194316

  2. The Alzheimer's disease neuroimaging initiative: perspectives of the Industry Scientific Advisory Board.

    PubMed

    Schmidt, Mark E; Siemers, Eric; Snyder, Peter J; Potter, William Z; Cole, Patricia; Soares, Holly

    2010-05-01

    The Industry Scientific Advisory Board (ISAB) consists of representatives from the private companies and nonprofit foundations participating as sponsors of Alzheimer's Disease Neuroimaging Initiative (ADNI). Currently 21 companies are represented including pharmaceutical, imaging, and biotech concerns, and two foundations including the Alzheimer's Association. ISAB members meet regularly by teleconference or face-to-face at ADNI meetings and participate in the ADNI Core groups, all administered and organized by the Foundation for the National Institutes of Health. ISAB 'deliverables' include dissemination of information to sponsors, assisting in scientific review of protocols and results, initiation and consideration of "add-on" studies and analyses, and generation of consensus positions on industry priorities and concerns. Although positioned as an advisory body, ISAB also actively contributes to the ADNI mission of identifying biomarkers of disease progression.

  3. PENN Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Shaw, Leslie M.

    2009-01-01

    There is a pressing need to develop effective prevention and disease-modifying treatments for Alzheimer’s disease (AD), a dreaded affliction whose incidence increases almost logarithmically with age starting at about 65 years. A key need in the field of AD research is the validation of imaging and biochemical biomarkers. Biomarker tests that are shown to reliably predict the disease before it is clinically expressed would permit testing of new therapeutics at the earliest time point possible in order to give the best chance for delaying the onset of dementia in these patients. In this review the current state of AD biochemical biomarker research is discussed. A new set of guidelines for the diagnosis of AD in the research setting places emphasis on the inclusion of selected imaging and biochemical biomarkers, in addition to neuropsychological behavioral testing. Importantly, the revised guidelines were developed to identify patients at the earliest stages prior to full-blown dementia as well as patients with the full spectrum of the disease. The Alzheimer’s Disease Neuroimaging Initiative is a multicenter consortium study that includes as one of its primary goals the development of standardized neuroimaging and biochemical biomarker methods for AD clinical trials, as well as using these to measure changes over time in mildly cognitively impaired patients who convert to AD as compared to the natural variability of these in control subjects and their further change over time in AD patients. Validation of the biomarker results by correlation analyses with neuropsychological and neurobehavioral test data is one of the primary outcomes of this study. This validation data will hopefully provide biomarker test performance needed for effective measurement of the efficacy of new treatment and prevention therapeutic agents. PMID:18097156

  4. Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Donohue, Michael C.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Thompson, Paul M.; Toga, Arthur W.; Trojanowski, John Q.

    2015-01-01

    Introduction The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer’s disease (AD) by validating biomarkers for AD clinical trials. Methods We searched for ADNI publications using established methods. Results ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson’s disease and multiple sclerosis. Discussion ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. PMID:26194320

  5. The Alzheimer’s Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

    PubMed Central

    Kang, Ju-Hee; Korecka, Magdalena; Figurski, Michal J.; Toledo, Jon B.; Blennow, Kaj; Zetterberg, Henrik; Waligorska, Teresa; Brylska, Magdalena; Fields, Leona; Shah, Nirali; Soares, Holly; Dean, Robert A.; Vanderstichele, Hugo; Petersen, Ronald C.; Aisen, Paul S.; Saykin, Andrew J.; Weiner, Michael W.; Trojanowski, John Q.; Shaw, Leslie M.

    2016-01-01

    Introduction We describe Alzheimer’s Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1–42), t-tau, and p-tau181 analytical performance, definition of Alzheimer’s disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids. Methods Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1–42, t-tau, and p-tau181 data. Results CSFAD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies. Discussion Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials. PMID:26194312

  6. The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans

    PubMed Central

    Weiner, Michael W.; Aisen, Paul S.; Jack, Clifford R.; Jagust, William J.; Trojanowski, John Q.; Shaw, Leslie; Saykin, Andrew J.; Morris, John C.; Cairns, Nigel; Beckett, Laurel A.; Toga, Arthur; Green, Robert; Walter, Sarah; Soares, Holly; Snyder, Peter; Siemers, Eric; Potter, William; Cole, Patricia E.; Schmidt, Mark

    2010-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer’s disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD. PMID:20451868

  7. Cerebrospinal Fluid Biomarker Signature in Alzheimer’s Disease Neuroimaging Initiative Subjects

    PubMed Central

    Shaw, Leslie M.; Vanderstichele, Hugo; Knapik-Czajka, Malgorzata; Clark, Christopher M.; Aisen, Paul S.; Petersen, Ronald C.; Blennow, Kaj; Soares, Holly; Simon, Adam; Lewczuk, Piotr; Dean, Robert; Siemers, Eric; Potter, William; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2009-01-01

    Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer’s disease (AD) in Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid-β 1 to 42 peptide (Aβ1-42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and Aβ1-42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. Results CSF Aβ1-42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1-42, t-tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/Aβ1-42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation The CSF biomarker signature of AD defined by Aβ1-42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. PMID:19296504

  8. Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Russo, María Julieta; Cohen, Gabriela; Chrem Mendez, Patricio; Campos, Jorge; Nahas, Federico E; Surace, Ezequiel I; Vazquez, Silvia; Gustafson, Deborah; Guinjoan, Salvador; Allegri, Ricardo F; Sevlever, Gustavo

    2016-01-01

    Purpose Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P<0.001, showing a continuum in their neuropsychological performance. No significant correlations were found between the principal measures (long-delay recall, C-Pittsburgh compound-B scan, left hippocampal volume, and APOEε4) and either age, sex, or education (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). Conclusion Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country. PMID:27695331

  9. Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

    PubMed Central

    Mueller, Susanne G.; Weiner, Michael W.; Thal, Leon J.; Petersen, Ronald C.; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel

    2007-01-01

    With the increasing life expectancy in developed countries, the incidence of Alzheimer’s disease (AD) and thus its socioeconomic impact are growing. Increasing knowledge over the last years about the pathomechanisms involved in AD allow for the development of specific treatment strategies aimed at slowing down or even preventing neuronal death in AD. However, this requires also that (1) AD can be diagnosed with high accuracy, because non-AD dementias would not benefit from an AD-specific treatment; (2) AD can be diagnosed in very early stages when any intervention would be most effective; and (3) treatment efficacy can be reliably and meaningfully monitored. Although there currently is no ideal biomarker that would fulfill all these requirements, there is increasing evidence that a combination of currently existing neuroimaging and cerebrospinal fluid (CSF) and blood biomarkers can provide important complementary information and thus contribute to a more accurate and earlier diagnosis of AD. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is exploring which combinations of these biomarkers are the most powerful for diagnosis of AD and monitoring of treatment effects. PMID:17476317

  10. Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

    PubMed

    Crane, Paul K; Carle, Adam; Gibbons, Laura E; Insel, Philip; Mackin, R Scott; Gross, Alden; Jones, Richard N; Mukherjee, Shubhabrata; Curtis, S McKay; Harvey, Danielle; Weiner, Michael; Mungas, Dan

    2012-12-01

    We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.

  11. A Computational Neurodegenerative Disease Progression Score: Method and Results with the Alzheimer’s Disease Neuroimaging Initiative Cohort

    PubMed Central

    Jedynak, Bruno M.; Lang, Andrew; Liu, Bo; Katz, Elyse; Zhang, Yanwei; Wyman, Bradley T.; Raunig, David; Jedynak, C. Pierre; Caffo, Brian; Prince, Jerry L.

    2012-01-01

    While neurodegenerative diseases are characterized by steady degeneration over relatively long timelines, it is widely believed that the early stages are the most promising for therapeutic intervention, before irreversible neuronal loss occurs. Developing a therapeutic response requires a precise measure of disease progression. However, since the early stages are for the most part asymptomatic, obtaining accurate measures of disease progression is difficult. Longitudinal databases of hundreds of subjects observed during several years with tens of validated biomarkers are becoming available, allowing the use of computational methods. We propose a widely applicable statistical methodology for creating a disease progression score (DPS), using multiple biomarkers, for subjects with a neurodegenerative disease. The proposed methodology was evaluated for Alzheimer’s disease (AD) using the publicly available AD Neuroimaging Initiative (ADNI) database, yielding an Alzheimer’s DPS or ADPS score for each subject and each time-point in the database. In addition, a common description of biomarker changes was produced allowing for an ordering of the biomarkers. The Rey Auditory Verbal Learning Test delayed recall was found to be the earliest biomarker to become abnormal. The group of biomarkers comprising the volume of the hippocampus and the protein concentration amyloid beta and Tau were next in the timeline, and these were followed by three cognitive biomarkers. The proposed methodology thus has potential to stage individuals according to their state of disease progression relative to a population and to deduce common behaviors of biomarkers in the disease itself. PMID:22885136

  12. 2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception.

    PubMed

    Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Cedarbaum, Jesse; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Luthman, Johan; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie; Shen, Li; Schwarz, Adam; Toga, Arthur W; Trojanowski, John Q

    2015-06-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers,

  13. The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2012-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade [1] and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most

  14. The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Shen, Li; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2014-01-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates

  15. The pilot European Alzheimer’s Disease Neuroimaging Initiative (E-ADNI) of the European Alzheimer’s Disease Consortium

    PubMed Central

    Frisoni, Giovanni B; Henneman, Wouter JP; Weiner, Michael W; Scheltens, Philip; Vellas, Bruno; Reynish, Emma; Hudecova, Jaroslava; Hampel, Harald; Burger, Katharina; Blennow, Kaj; Waldemar, Gunhild; Johannsen, Peter; Wahlund, Lars-Olof; Zito, Giancarlo; Rossini, Paolo M; Winblad, Bengt; Barkhof, Frederik

    2008-01-01

    Background In North-America, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer’s disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). Methods Seven academic sites of the European Alzheimer’s Disease Consortium (EADC) enrolled 19 patients with MCI, 22 with AD, and 18 older healthy persons using the ADNI clinical and neuropsychological battery. ADNI compliant MR scans, CSF and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater using visual rating scales. Results Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioural and neuropsychological features of the European subjects were very similar to their US counterparts. 3D T1-weighted MRI sequences were successfully performed on all subjects and CSF samples obtained from 77%, 68%, and 83% of AD, MCI, and controls. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI (0.9, 0.8) to AD (2.3, 2.0), while mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US ADNI subjects. Conclusions Academic EADC centres can adopt the ADNI platform to enrol MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US ADNI. PMID:18631976

  16. Perspective: The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partner Scientific Board (PPSB).

    PubMed

    Liu, Enchi; Luthman, Johan; Cedarbaum, Jesse M; Schmidt, Mark E; Cole, Patricia E; Hendrix, James; Carrillo, Maria C; Jones-Davis, Dorothy; Tarver, Erika; Novak, Gerald; De Santi, Susan; Soares, Holly D; Potter, William Z; Siemers, Eric; Schwarz, Adam J

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partner Scientific Board (PPSB) is comprised of representatives of private, for-profit entities (including pharmaceutical, biotechnology, diagnostics, imaging companies, and imaging contract research organizations), and nonprofit organizations that provide financial and scientific support to ADNI through the Foundation for the National Institutes of Health. The PPSB serves as an independent, open, and precompetitive forum in which all private sector and not-for-profit partners in ADNI can collaborate, share information, and offer scientific and private-sector perspectives and expertise on issues relating to the ADNI project. In this article, we review and highlight the role, activities, and contributions of the PPSB within the ADNI project, and provide a perspective on remaining unmet needs and future directions.

  17. Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina-Alzheimer’s Disease Neuroimaging Initiative)

    PubMed Central

    Harris, Paula; Fernandez Suarez, Marcos; Surace, Ezequiel I; Chrem Méndez, Patricio; Martín, María Eugenia; Clarens, María Florencia; Tapajóz, Fernanda; Russo, Maria Julieta; Campos, Jorge; Guinjoan, Salvador M; Sevlever, Gustavo; Allegri, Ricardo F

    2015-01-01

    Background The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer’s disease, and in control subjects. Methods Thirty-three participants from the Argentina-Alzheimer’s Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. Results The CRQ significantly correlated with TAP-BA, education, and Aβ1-42. When considering Aβ1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aβ1-42 were associated with higher CRQ scores. Conclusion Reduced Aβ1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer’s disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aβ1-42 levels in individuals with more cognitive reserve. PMID:26504392

  18. Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Madsen, Sarah K; Rajagopalan, Priya; Joshi, Shantanu H; Toga, Arthur W; Thompson, Paul M

    2015-01-01

    A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor, high-homocysteine levels in the blood, is known to increase risk for Alzheimer's disease and vascular disorders. Here, we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, and surface area) computed from brain magnetic resonance imaging in 803 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative data set. Individuals with higher plasma levels of homocysteine had lower gray matter thickness in bilateral frontal, parietal, occipital, and right temporal regions and lower gray matter volumes in left frontal, parietal, temporal, and occipital regions, after controlling for diagnosis, age, and sex and after correcting for multiple comparisons. No significant within-group associations were found in cognitively healthy people, patients with mild cognitive impairment, or patients with Alzheimer's disease. These regional differences in gray matter structure may be useful biomarkers to assess the effectiveness of interventions, such as vitamin B supplements, that aim to prevent homocysteine-related brain atrophy by normalizing homocysteine levels.

  19. A composite score for executive functioning, validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment.

    PubMed

    Gibbons, Laura E; Carle, Adam C; Mackin, R Scott; Harvey, Danielle; Mukherjee, Shubhabrata; Insel, Philip; Curtis, S McKay; Mungas, Dan; Crane, Paul K

    2012-12-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) measures abilities broadly related to executive function (EF), including WAIS-R Digit Symbol Substitution, Digit Span Backwards, Trails A and B, Category Fluency, and Clock Drawing. This study investigates whether a composite executive function measure based on these multiple indicators has better psychometric characteristics than the widely used individual components. We applied item response theory methods to 800 ADNI participants to derive an EF composite score (ADNI-EF) from the above measures. We then compared ADNI-EF with component measures in 390 longitudinally-followed participants with mild cognitive impairment (MCI) with respect to: (1) Ability to detect change over time; (2) Ability to predict conversion to dementia; (3) Strength of cross-sectional association with MRI-derived measures of structures involved in frontal systems, and (4) Strength of baseline association with cerebrospinal fluid (CSF) levels of amyloid β₁₋₄₂, total tau, and phosphorylated tau(181P). ADNI-EF showed the greatest change over time, followed closely by Category Fluency. ADNI-EF needed a 40 % smaller sample size to detect change. ADNI-EF was the strongest predictor of AD conversion. ADNI-EF was the only measure significantly associated with all the MRI regions, though other measures were more strongly associated in a few of the regions. ADNI-EF was associated with all the CSF measures. ADNI-EF appears to be a useful composite measure of EF in MCI, as good as or better than any of its composite parts. This study demonstrates an approach to developing a psychometrically sophisticated composite score from commonly-used tests.

  20. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Weiner, Michael W; Veitch, Dallas P; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford; Jagust, William; Trojanowski, John Q; Shaw, Leslie M; Saykin, Andrew J; Green, Robert C; Harvey, Danielle; Toga, Arthur W; Friedl, Karl E; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2014-06-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  1. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Russo, María J; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ(2) = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

  2. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative

    PubMed Central

    Russo, María J.; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F.; Weiner, Michael W.

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI. PMID:28344552

  3. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    PubMed Central

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

  4. The impact of the Alzheimer's Disease Neuroimaging Initiative 2: What role do public-private partnerships have in pushing the boundaries of clinical and basic science research on Alzheimer's disease?

    PubMed

    Jones-Davis, Dorothy M; Buckholtz, Neil

    2015-07-01

    In the growing landscape of biomedical public-private-partnerships, particularly for Alzheimer's disease, the question is posed as to their value. What impacts do public-private-partnerships have on clinical and basic science research in Alzheimer's disease? The authors answer the question using the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a test case and example. ADNI is an exemplar of how public-private-partnerships can make an impact not only on clinical and basic science research and practice (including clinical trials), but also of how similar partnerships using ADNI as an example, can be designed to create a maximal impact within their fields.

  5. Low plasma ApoE levels are associated with smaller hippocampal size in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort

    PubMed Central

    Teng, Edmond; Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Gylys, Karen H.; Cole, Gregory M.; Jack, Clifford R.; Shaw, Leslie M.; Trojanowski, John Q.; Soares, Holly D.; Weiner, Michael W.; Apostolova, Liana G.

    2014-01-01

    Apoliproprotein E (APOE) genotype is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging (MRI) indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an APOE ε4 allele, and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals. PMID:25547651

  6. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).

    PubMed

    Cairns, Nigel J; Perrin, Richard J; Franklin, Erin E; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M; McLean, Catriona; Ghetti, Bernardino; Morris, John C

    2015-08-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared.

  7. Structural Neuroimaging Genetics Interactions in Alzheimer’s Disease

    PubMed Central

    Moon, Seok Woo; Dinov, Ivo D.; Kim, Jaebum; Zamanyan, Alen; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

    2016-01-01

    This article investigates late-onset cognitive impairment using neuroimaging and genetics biomarkers for subjects participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Eight hundred and eight ADNI subjects were identified and divided into three groups: those with Alzheimer’s Disease (AD), those with mild cognitive impairment (MCI), and asymptomatic normal control (NC) group. Two hundred of the subjects qualified for AD diagnosis at the baseline; three hundred and eighty-three had MCI; and 225 were included in the NC group. The structural magnetic resonance imaging (MRI) data were parcellated using BrainParser, and the 80 most important neuroimaging biomarkers were extracted using the Global Shape Analysis (GSA) Pipeline workflow. We obtained 80 SNPs using Plink analysis via the Pipeline environment. In the AD cohort, rs2137962 was significantly associated with changes in left and right hippocampi and bilaterally in parahippocampal gyri, and rs1498853, rs288503, and rs288496 were significantly associated with hippocampi bilaterally, the right parahippocampal gyrus, and left inferior temporal gyrus. In the MCI cohort, rs17028008 and rs17027976 were significantly associated with right caudate and right fusiform gyrus, and rs2075650 (TOMM40) was significantly associated with right caudate, rs1334496 and rs4829605 were significantly associated with right inferior temporal gyrus. In the NC cohort, Chromosome 15 [rs734854 (STOML1), rs11072463 (PML), rs4886844 (PML) and rs1052242 (PML)] was significantly associated with the both hippocampi and both insular cortex and rs4899412 (RGS6) was significantly associated with caudate related biomarkers. We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 808 subjects in terms of neuroimaging genetics. These results illustrate some of the neuroimaging-genetics associations between the AD, MCI and NC cohorts. PMID:26444770

  8. Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

    PubMed

    Savage, Mary J; Holder, Daniel J; Wu, Guoxin; Kaplow, June; Siuciak, Judith A; Potter, William Z

    2015-01-01

    β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-β (Aβ) N-terminus from the amyloid-β protein precursor (AβPP), the first step in Aβ formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sAβPPβ, the N-terminal secreted product of BACE1 (sBACE1) activity on AβPP. Here, sBACE1 enzymatic activity and secreted AβPPβ (sAβPPβ) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sAβPPβ demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aβ peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aβ₄₂ and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAβPPβ concentrations can be used to differentiate between healthy elderly and AD individuals.

  9. Neuroimaging in Alzheimer disease: an evidence-based review.

    PubMed

    Kantarci, Kejal; Jack, Clifford R

    2003-05-01

    Current clinical criteria (DSM-IIIR and NINCDS-ADRDA) for the diagnosis of dementia and AD are reliable; however, these criteria remain to be validated by clinicians of different levels of expertise at different clinical settings. Structural neuroimaging has an important role in initial evaluation of dementia for ruling out potentially treatable causes. Although CT is the appropriate choice when brain tumors, subdural hematoma, or normal pressure hydrocephalus is suspected, MR imaging is more sensitive to the white-matter changes in vascular dementia. The diagnostic accuracy of PET, SPECT, 1H MRS, and MR volumetry of the hippocampus for distinguishing patients with AD from healthy elderly individuals is comparable to the accuracy of a pathologically confirmed clinical diagnosis. Sensitivity of PET for distinguishing patients with dementia with Lewy bodies from AD, however, is higher than that of clinical evaluation; similarly, SPECT and 1H MRS may be adjuncts to clinical evaluation for distinguishing patients with frontotemporal dementia from those with AD. Neuroimaging is valuable in predicting future development of AD in patients with MCI and in carriers of the ApoE epsilon 4 allele who are at a higher risk of developing AD than are cognitively normal elderly individuals. Quantitative MR techniques (e.g., MR volumetry, DWI, magnetization transfer MR imaging, and 1H MRS) and PET are sensitive to the structural and functional changes in the brains of patients with MCI, and hippocampal volumes on MR imaging are associated with future development of AD in these individuals. PET is also sensitive to the regional metabolic decline in the brains of carriers of the ApoE epsilon 4 allele. The longitudinal decrease of whole brain and hippocampal volumes on MR imaging, NAA levels on 1H MRS, cerebral glucose metabolism on PET, and cerebral blood flow on SPECT are associated with rate of cognitive decline in patients with AD. These neuroimaging markers may be useful for

  10. Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical efficacy.

    PubMed

    Dustin, Derek; Hall, Benjamin M; Annapragada, Ananth; Pautler, Robia G

    2016-09-01

    The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal-based MRI contrast agents as well as fluorine 19 ((19)F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic.

  11. Neuroimaging of Parkinson’s Disease: Expanding views

    PubMed Central

    Weingarten, Carol P.; Sundman, Mark H.; Hickey, Patrick; Chen, Nankuei

    2015-01-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. PMID:26409344

  12. Alzheimer's disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition.

    PubMed

    Leow, Alex D; Yanovsky, Igor; Parikshak, Neelroop; Hua, Xue; Lee, Suh; Toga, Arthur W; Jack, Clifford R; Bernstein, Matt A; Britson, Paula J; Gunter, Jeffrey L; Ward, Chadwick P; Borowski, Bret; Shaw, Leslie M; Trojanowski, John Q; Fleisher, Adam S; Harvey, Danielle; Kornak, John; Schuff, Norbert; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2009-04-15

    Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental state exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (ABeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail.

  13. A review of β-amyloid neuroimaging in Alzheimer's disease

    PubMed Central

    Adlard, Paul A.; Tran, Bob A.; Finkelstein, David I.; Desmond, Patricia M.; Johnston, Leigh A.; Bush, Ashley I.; Egan, Gary F.

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments. Neuroimaging has enabled in vivo visualization of pathological changes in the brain associated with the disease, providing a greater understanding of its pathophysiological development and progression. However, neuroimaging biomarkers do not yet offer clear advantages over current clinical diagnostic criteria for them to be accepted into routine clinical use. Nonetheless, current insights from neuroimaging combined with the elucidation of biochemical and molecular processes in AD are informing the ongoing development of new imaging techniques and their application. Much of this research has been greatly assisted by the availability of transgenic mouse models of AD. In this review we summarize the main efforts of neuroimaging in AD in humans and in mouse models, with a specific focus on β-amyloid, and discuss the potential of new applications and novel approaches. PMID:25400539

  14. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    PubMed Central

    Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

  15. Neuroimaging of spinal diseases: a pictorial review.

    PubMed

    Kasdan, Richard B; Howard, Jaime L

    2008-09-01

    Magnetic resonance imaging (MRI) has become a valuable noninvasive, cost-effective tool for accurately evaluating spine disorders. This article affords a comprehensive review of normal anatomy as it relates to MRI interpretation with specific attention to accurately defining nerve root abnormalities. It gives in-depth detail on disc herniation nomenclature with specific examples of disc bulge, disc protrusion, disc extrusion, and disc sequestration. In addition, there are illustrations of various forms of degenerative spine disease, including intradiscal degenerative disease, reactive end plate changes, spinal stenosis, synovial cyst formation, and spinal instability. Differentiating features for separating osteoporotic spine fracture from underlying neoplastic pathologic fracture are illustrated. Finally, examples of both benign and malignant disease are illustrated in the spine with corresponding clinical and MRI examples.

  16. Cross-View Neuroimage Pattern Analysis in Alzheimer's Disease Staging

    PubMed Central

    Liu, Sidong; Cai, Weidong; Pujol, Sonia; Kikinis, Ron; Feng, Dagan D.

    2016-01-01

    The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD), is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC) to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed nine types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI, and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging. PMID:26941639

  17. [Neuroimaging for patients with Alzheimer disease in routine practice].

    PubMed

    Matsuda, Hiroshi

    2010-07-01

    In routine practice neuroimaging has been applied as an adjunct technique for early and differential diagnosis of Alzheimer disease in routine practice. Of the several neuroimaging modalities, magnetic resonance imaging (MRI) and brain perfusion single-photon emission computed tomography (SPECT) have been commonly used in Japan; further software programs are used to aid statistical analysis of the imaging results. For example voxel-based specific regional analysis system for Alzheimer disease (VSRAD) for MRI and easy Z-score imaging system (eZIS) are used for the analysis of MRI and SPECT. In the early stage of Alzheimer disease, specific findings of regional atrophy and perfusion reduction are observed in some areas. In the posterior cingulate gyrus precuneus and parietal cortex, perfusion reduction was more frequently observed than atrophy. On the other hand, in the medial temporal structures, perfusion reduction was less frequently observed than atrophy. Perfusion reduction in the the posterior cingulate gyrus precuneus and in the parietal cortex was more prominent in the case of patients with early-onset Alzheimer disease than in the case of patients with late-onset Alzheimer disease. Further, atrophy in the medial temporal structures was more prominent in the case of patients with late-onset Alzheimer disease than in the case of those with early-onset Alzheimer disease. These findings are helpful for differentiating of Alzheimer disease from other diseases characterized by dementia.

  18. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease.

    PubMed

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

  19. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  20. Neuroimaging studies of striatum in cognition part II: Parkinson's disease

    PubMed Central

    Hanganu, Alexandru; Provost, Jean-Sebastien; Monchi, Oury

    2015-01-01

    In recent years a gradual shift in the definition of Parkinson's disease (PD) has been established, from a classical akinetic-rigid movement disorder to a multi-system neurodegenerative disease. While the pathophysiology of PD is complex and goes much beyond the nigro-striatal degeneration, the striatum has been shown to be responsible for many cognitive functions. Patients with PD develop impairments in multiple cognitive domains and the PD model is probably the most extensively studied regarding striatum dysfunction and its influence on cognition. Up to 40% of PD patients present cognitive impairment even in the early stages of disease development. Thus, understanding the key patterns of striatum and connecting regions' influence on cognition will help develop more specific approaches to alleviate cognitive impairment and slow down its decline. This review focuses on the contribution of neuroimaging studies in understanding how striatum impairment affects cognition in PD. PMID:26500512

  1. Neuroimaging enrichment strategy for secondary prevention trials in Alzheimer disease.

    PubMed

    McEvoy, Linda K; Edland, Steven D; Holland, Dominic; Hagler, Donald J; Roddey, J Cooper; Fennema-Notestine, Christine; Salmon, David P; Koyama, Alain K; Aisen, Paul S; Brewer, James B; Dale, Anders M

    2010-01-01

    We examined the improvement in statistical power that could be obtained in therapeutic trials for early (predementia) Alzheimer disease by constraining enrollment to individuals with amnestic mild cognitive impairment (MCI) and an atrophy pattern on a screening magnetic resonance imaging (MRI) scan previously found to be predictive of clinical decline, or to individuals with MCI and the apolipoprotein E epsilon 4 genetic risk factor for Alzheimer disease. Treatable effects were defined as absolute change versus change relative to healthy controls (HCs). Data from 168 HC and 299 MCI participants were analyzed to determine sample sizes required to detect 25% slowing in mean rate of decline using global function, cognitive function, and structural measures as outcome variables. Reductions in estimated sample sizes of 10% to 43% were observed using the genetic enrichment strategy; reductions of 43% to 60% were observed with the neuroimaging enrichment strategy. Sample sizes needed to detect slowing in rate of atrophy in MCI relative to HC were dramatically larger than those needed to detect absolute change in atrophy rates. Constraining enrollment to MCI subjects with predictive atrophy on a screening MRI scan could improve the efficiency of clinical trials. Failure to take into account normal age-related changes risks under-powering trials designed to test disease-modifying properties of potential treatments.

  2. Neuroimaging and the search for a cure for Alzheimer disease.

    PubMed

    Petrella, Jeffrey R

    2013-12-01

    As radiologists, our role in the workup of the dementia patient has long been limited by the sensitivity of our imaging tools and lack of effective treatment options. Over the past 30 years, we have made tremendous strides in understanding the genetic, molecular, and cellular basis of Alzheimer disease (AD). We now know that the pathologic features of AD are present 1 to 2 decades prior to development of symptoms, though currently approved symptomatic therapies are administered much later in the disease course. The search for true disease-modifying therapy continues and many clinical trials are underway. Current outcome measures, based on cognitive tests, are relatively insensitive to pathologic disease progression, requiring long, expensive trials with large numbers of participants. Biomarkers, including neuroimaging, have great potential to increase the power of trials by matching imaging methodology with therapeutic mechanism. One of the most important advances over the past decade has been the development of in vivo imaging probes targeted to amyloid beta protein, and one agent is already available for clinical use. Additional advances include automated volumetric imaging methods to quantitate cerebral volume loss. Use of such techniques in small, early phase trials are expected to significantly increase the number and quality of candidate drugs for testing in larger trials. In addition to a critical role in trials, structural, molecular, and functional imaging techniques can give us a window on the etiology of AD and other neurodegenerative diseases. This combination of developments has potential to bring diagnostic radiology to the forefront in AD research, therapeutic trials, and patient care.

  3. Neuroimaging correlates of cognitive impairment and dementia in Parkinson's disease.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2015-08-01

    There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.

  4. Structural Neuroimaging of the Medial Temporal Lobe in Alzheimer's Disease Clinical Trials.

    PubMed

    Menéndez-González, Manuel; de Celis Alonso, Benito; Salas-Pacheco, José; Arias-Carrión, Oscar

    2015-01-01

    Atrophy in the medial temporal lobe (MTA) is being used as a criterion to support a diagnosis of Alzheimer's disease (AD). There are several structural neuroimaging approaches for quantifying MTA, including semiquantitative visual rating scales, volumetry (3D), planimetry (2D), and linear measures (1D). Current applications of structural neuroimaging in Alzheimer's disease clinical trials (ADCTs) incorporate it as a tool for improving the selection of subjects for enrollment or for stratification, for tracking disease progression, or providing evidence of target engagement for new therapeutic agents. It may also be used as a surrogate marker, providing evidence of disease-modifying effects. However, despite the widespread use of volumetric magnetic resonance imaging (MRI) in ADCTs, there are some important challenges and limitations, such as difficulties in the interpretation of results, limitations in translating results into clinical practice, and reproducibility issues, among others. Solutions to these issues may arise from other methodologies that are able to link the results of volumetric MRI from trials with conventional MRIs performed in routine clinical practice (linear or planimetric methods). Also of potential benefit are automated volumetry, using indices for comparing the relative rate of atrophy of different regions instead of absolute rates of atrophy, and combining structural neuroimaging with other biomarkers. In this review, authors present the existing structural neuroimaging approaches for MTA quantification. They then discuss solutions to the limitations of the different techniques as well as the current challenges of the field. Finally, they discuss how the current advances in AD neuroimaging can help AD diagnosis.

  5. Evolution of autobiographical memory impairments in Alzheimer's disease and frontotemporal dementia - A longitudinal neuroimaging study.

    PubMed

    Irish, Muireann; Landin-Romero, Ramon; Mothakunnel, Annu; Ramanan, Siddharth; Hsieh, Sharpley; Hodges, John R; Piguet, Olivier

    2017-03-10

    Compromised autobiographical memory (ABM) retrieval is well established in dementia, attributable to degeneration of a core memory brain network. It remains unclear, however, how the progressive spread of atrophy with advancing disease severity impacts ABM retrieval across life epochs. To this end, we conducted a longitudinal study of recent and remote ABM in Alzheimer's disease (AD, n =11), and a frontotemporal lobar degeneration group (FTD, n =13) comprising 7 behavioral variant FTD and 6 semantic dementia patients, in comparison with 23 healthy older Controls. Patients were re-assessed approximately one year following their initial visit and underwent repeat testing and brain imaging. Linear mixed modeling neuroimaging analyses explored disease-specific cortical changes driving ABM alterations over time. AD patients showed comparable ABM profiles across assessment periods however, follow-up performance correlated strongly with lateral temporal lobe integrity. In contrast, recent ABMs were disproportionately disrupted at follow-up relative to baseline in the FTD group, attributable to cortical thinning in posterior brain regions, including the right posterior cingulate cortex. Our findings offer new insights regarding the potential time-specific role of discrete cortical regions in ABM retrieval and the differential fate of formerly evocative memories with advancing disease severity in dementia syndromes.

  6. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    PubMed

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

  7. Physiological fluctuations in white matter are increased in Alzheimer's disease and correlate with neuroimaging and cognitive biomarkers.

    PubMed

    Makedonov, Ilia; Chen, J Jean; Masellis, Mario; MacIntosh, Bradley J

    2016-01-01

    The objective of this study was to determine whether physiological fluctuations in white matter (PFWM) on resting-state functional magnetic resonance images could be used as an index of neurodegeneration and Alzheimer's disease (AD). Using resting-state functional magnetic resonance image data from participants in the Alzheimer's Disease Neuroimaging Initiative, PFWM was compared across cohorts: cognitively healthy, mild cognitive impairment, or probable AD. Secondary regression analyses were conducted between PFWM and neuroimaging, cognitive, and cerebrospinal fluid biomarkers. There was an effect of cohort on PFWM (t = 5.08, degree of freedom [df] = 424, p < 5.7 × 10(-7)), after accounting for nuisance effects from head displacement and global signal (t > 6.16). From the neuroimaging data, PFWM was associated with glucose metabolism (t = -2.93, df = 96, p = 0.004) but not ventricular volume (p < 0.49) or hippocampal volume (p > 0.44). From the cognitive data, PFWM was associated with composite memory (t = -3.24, df = 149, p = 0.0015) but not executive function (p > 0.21). PFWM was not associated with cerebrospinal fluid biomarkers. In one final omnibus model to explain PFWM (n = 124), glucose metabolism (p = 0.04) and cohort (p = 0.008) remained significant, as were global and head motion root-mean-square terms, whereas memory was not (p = 0.64). PFWM likely reflects end-arteriole intracranial pulsatility effects that may provide additional diagnostic potential in the context of AD neurodegeneration.

  8. Multimodal neuroimaging of male and female brain structure in health and disease across the life span

    PubMed Central

    Thompson, Paul M.

    2016-01-01

    Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:27870421

  9. The Use of Neuroimaging in the Diagnosis of Mitochondrial Disease

    ERIC Educational Resources Information Center

    Friedman, Seth D.; Shaw, Dennis W. W.; Ishak, Gisele; Gropman, Andrea L.; Saneto, Russell P.

    2010-01-01

    Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation…

  10. Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

    PubMed

    Esopenko, Carrie; Levine, Brian

    2015-02-15

    Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

  11. The role of neuroimaging in the early diagnosis and evaluation of Parkinson's disease.

    PubMed

    Seibyl, J; Jennings, D; Tabamo, R; Marek, K

    2005-10-01

    The development of imaging biomarkers which target specific sites in the brain represents a significant advance in neurodegenerative diseases and Parkinson's disease with the promise of new and improved approaches for the early and accurate diagnosis of disease as well as novel ways to monitor patients and assess treatment. The 3 major applications of imaging may play a role in Parkinson's disease include: 1) the use of neuroimaging as a biomarker of disease in order to improve the accuracy, timeliness, and reliability of diagnosis; 2) objective monitoring of the progression of disease to provide a molecular phenotype of Parkinson's disease which may illuminate some of the sources of clinical variability; 3) the evaluation of so-called ''disease-modifying'' treatments designed to retard the progression of disease by interfering with pathways thought implicated in the ongoing neuronal loss or replace dopamine-producing cells. Each of these areas has shown a numbers of critical clinical investigations which have better defined the utility of the imaging tools to these tasks. Nonetheless, current unresolved issues around the clinical role of neuroimaging in monitoring patients over time and validation of quantitative imaging measures of dopaminergic function are immediate issues for the field and the subject of current research efforts and the extension of the lessons learned in Parkinson's to other neurodegenerative diseases including Alzheimer's dementia.

  12. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease

    PubMed Central

    Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

    2016-01-01

    Abstract Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings. The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and analyzed. Denervation changes in any single C5 to C7 root-innervated muscle (deltoid, biceps, triceps, or extensor digitorum communis) occurred more frequently in the 25 patients with cord atrophy than the 19 patients without cord atrophy (88% vs 53%, P = 0.02). Onset age, duration of disease progression, neurological examinations, nerve conduction study, and electromyographic findings from individual muscles were similar between patient groups. Compared with HD patients without cord atrophy, HD patients with cord atrophy experience a more severe denervation change in C5 to C7 root-innervated muscles. PMID:27428223

  13. Brain structure and function related to depression in Alzheimer's disease: contributions from neuroimaging research.

    PubMed

    Brommelhoff, Jessica A; Sultzer, David L

    2015-01-01

    The development of minimally invasive in vivo methods for imaging the brain has allowed for unprecedented advancement in our understanding of brain-behavior relationships. Structural, functional, and multimodal neuroimaging techniques have become more sophisticated in detecting structural and physiological abnormalities that may underlie various affective disorders and neurological illnesses such as depression in Alzheimer's disease (AD). In general, neuroimaging studies of depression in AD investigate whether depression is associated with damage to structures in specific neural networks involving frontal and subcortical structures or with functional disruption of cortical neural systems. This review provides an overview of how various imaging modalities have contributed to our understanding of the neurobiology of depression in AD. At present, the literature does not conclusively support any specific pathogenesis for depression, and it is not clear whether patients with AD and depression have histopathological and neurochemical characteristics that contribute to mood symptoms that are different from cognitively intact individuals with depression. Neuroimaging studies suggest that atrophy of temporal or frontal structures, white matter lesions in frontal lobe or subcortical systems, reduced activity in dorsolateral frontal cortex, or small vessel cerebrovascular disease may be associated with depression in AD. Conceptual, clinical, and methodological challenges in studying this relationship are discussed. Further work is needed to understand the specific brain structures, relevant white matter tracts, and interactions among them that are most important. This review concludes with potential directions for future research.

  14. The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques.

    PubMed

    Li, Tie-Qiang; Wahlund, Lars-Olof

    2011-03-01

    The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel-based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS).

  15. Multimodal Neuroimaging Feature Learning with Multimodal Stacked Deep Polynomial Networks for Diagnosis of Alzheimer's Disease.

    PubMed

    Shi, Jun; Zheng, Xiao; Li, Yan; Zhang, Qi; Ying, Shihui

    2017-01-19

    The accurate diagnosis of Alzheimer's disease (AD) and its early stage, i.e. mild cognitive impairment (MCI), is essential for timely treatment and possible delay of AD. Fusion of multimodal neuroimaging data, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), has shown its effectiveness for AD diagnosis. The deep polynomial networks (DPN) is a recently proposed deep learning algorithm, which performs well on both large-scale and small-size datasets. In this study, a multimodal stacked DPN (MM-SDPN) algorithm, which MM-SDPN consists of two-stage SDPNs, is proposed to fuse and learn feature representation from multimodal neuroimaging data for AD diagnosis. Specifically speaking, two SDPNs are first used to learn high-level features of MRI and PET, respectively, which are then fed to another SDPN to fuse multimodal neuroimaging information. The proposed MM-SDPN algorithm is applied to the ADNI dataset to conduct both binary classification and multiclass classification tasks. Experimental results indicate that MM-SDPN is superior over the state-of-the-art multimodal feature learning based algorithms for AD diagnosis.

  16. Applied Neuroimaging to the Diagnosis of Alzheimer's Disease: A Multicriteria Model

    NASA Astrophysics Data System (ADS)

    Tamanini, Isabelle; de Castro, Ana Karoline; Pinheiro, Plácido Rogério; Pinheiro, Mirian Calíope Dantas

    In the last few years, Alzheimer's disease has been the most frequent cause of dementia and it is responsible, alone or in association with other diseases, for 50% of the cases in western countries. Dementias are syndromes characterized by a decline in memory and other neuropsychological changes, especially occurring in elderly people and increasing exponentially along the aging process. The main focus of this work is to develop a multicriteria model for aiding in decision making on the diagnosis of Alzheimer's disease by using the Aranau Tool, structured on the Verbal Decision Analysis. In this work, the modeling and evaluation processes were conducted with the aid of a medical expert, bibliographic sources and questionnaires. The questionnaires taken into account were based mainly on patients' neuroimaging tests, and we analyzed wheter or not there were problems in the patients' brain that could be relevant to the diagnosis of Alzheimer's disease.

  17. Multi-Modal Neuroimaging Feature Learning for Multi-Class Diagnosis of Alzheimer’s Disease

    PubMed Central

    Liu, Siqi; Liu, Sidong; Cai, Weidong; Che, Hangyu; Pujol, Sonia; Kikinis, Ron; Feng, Dagan; Fulham, Michael J.

    2015-01-01

    The accurate diagnosis of Alzheimers disease (AD) is essential for patient care and will be increasingly important as disease modifying agents become available, early in the course of the disease. Although studies have applied machine learning methods for the computer aided diagnosis (CAD) of AD, a bottleneck in the diagnostic performance was shown in previous methods, due to the lacking of efficient strategies for representing neuroimaging biomarkers. In this study, we designed a novel diagnostic framework with deep learning architecture to aid the diagnosis of AD. This framework uses a zero-masking strategy for data fusion to extract complementary information from multiple data modalities. Compared to the previous state-of-the-art workflows, our method is capable of fusing multi-modal neuroimaging features in one setting and has the potential to require less labelled data. A performance gain was achieved in both binary classification and multi-class classification of AD. The advantages and limitations of the proposed framework are discussed. PMID:25423647

  18. Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.

    PubMed

    Locascio, Joseph J; Eberly, Shirley; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Hung, Albert Y; Flaherty, Alice W; Schwarzschild, Michael A; Hayes, Michael T; Wills, Anne-Marie; Shivraj Sohur, U; Mejia, Nicte I; Selkoe, Dennis J; Oakes, David; Shoulson, Ira; Dong, Xianjun; Marek, Ken; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T; Growdon, John H; Sudarsky, Lewis R; Schlossmacher, Michael G; Ravina, Bernard; Scherzer, Clemens R

    2015-09-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

  19. Contribution of neuroimaging to the diagnosis of Alzheimer's disease and vascular dementia.

    PubMed

    Román, Gustavo; Pascual, Belén

    2012-11-01

    The aim of this study was to review, summarize and analyze recent findings relevant to the contribution of neuroimaging to the diagnosis of Alzheimer's disease (AD) and vascular dementia (VaD). Computerized tomography (CT) or magnetic resonance imaging (MRI) provide accurate demonstration of the location and rate of progression of atrophic changes affecting the brain in AD and the different types of vascular lesions observed in mixed dementias and in pure VaD. Quantification of cortical thickness allows early diagnosis and rate of progression from mild cognitive impairment (MCI) to dementia. White matter involvement can also be quantified with diffusion tensor imaging (DTI) and functional methods including fMRI, functional connectivity, and MR spectroscopy (MRS). Isotope-based techniques such as positron emission tomography (PET) allow measurement of regional cerebral glucose metabolism using (18)F-2-fluoro-deoxy-D-glucose (FDG). Cerebral blood flow can be measured using PET with H(2)(15)O or with single photon emission computerized tomography (SPECT) with technetium ((99m)Tc-HMPAO) or, more recently, arterial spin label (ASL) imaging. There are isotope markers for amyloid-beta ((11)O-PIB, (18)F-florbetapir), tau ((18)FDDNP) and activated microglia ((11)C-PK11195). Neuroimaging markers are particularly useful at the early symptomatic and preclinical asymptomatic phases of AD, as well as serving as endpoints in clinical trials.

  20. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  1. The behavioural/dysexecutive variant of Alzheimer’s disease: clinical, neuroimaging and pathological features

    PubMed Central

    Pijnenburg, Yolande A. L.; Perry, David C.; Cohn-Sheehy, Brendan I.; Scheltens, Nienke M. E.; Vogel, Jacob W.; Kramer, Joel H.; van der Vlies, Annelies E.; Joie, Renaud La; Rosen, Howard J.; van der Flier, Wiesje M.; Grinberg, Lea T.; Rozemuller, Annemieke J.; Huang, Eric J.; van Berckel, Bart N. M.; Miller, Bruce L.; Barkhof, Frederik; Jagust, William J.; Scheltens, Philip; Seeley, William W.; Rabinovici, Gil D.

    2015-01-01

    A ‘frontal variant of Alzheimer’s disease’ has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer’s disease pathology. The description of this rare Alzheimer’s disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer’s disease with a behavioural-predominant presentation (behavioural Alzheimer’s disease) and a neuropathological diagnosis of high-likelihood Alzheimer’s disease (n = 17) and/or biomarker evidence of Alzheimer’s disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer’s disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer’s disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer’s disease: 53%; dysexecutive Alzheimer’s disease: 83%) than behavioural (behavioural Alzheimer’s disease: 25%; dysexecutive Alzheimer’s disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer’s disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer’s disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer’s disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer’s disease (typical Alzheimer’s disease, n = 58), autopsy-confirmed/Alzheimer’s disease biomarker-negative behavioural

  2. Identification of Early-Stage Alzheimer's Disease Using Sulcal Morphology and Other Common Neuroimaging Indices

    PubMed Central

    Cai, Kunpeng; Xu, Hong; Guan, Hao; Zhu, Wanlin; Jiang, Jiyang; Cui, Yue; Zhang, Jicong; Liu, Tao; Wen, Wei

    2017-01-01

    Identifying Alzheimer’s disease (AD) at its early stage is of major interest in AD research. Previous studies have suggested that abnormalities in regional sulcal width and global sulcal index (g-SI) are characteristics of patients with early-stage AD. In this study, we investigated sulcal width and three other common neuroimaging morphological measures (cortical thickness, cortical volume, and subcortical volume) to identify early-stage AD. These measures were evaluated in 150 participants, including 75 normal controls (NC) and 75 patients with early-stage AD. The global sulcal index (g-SI) and the width of five individual sulci (the superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure) were extracted from 3D T1-weighted images. The discriminative performances of the other three traditional neuroimaging morphological measures were also examined. Information Gain (IG) was used to select a subset of features to provide significant information for separating NC and early-stage AD subjects. Based on the four modalities of the individual measures, i.e., sulcal measures, cortical thickness, cortical volume, subcortical volume, and combinations of these individual measures, three types of classifiers (Naïve Bayes, Logistic Regression and Support Vector Machine) were applied to compare the classification performances. We observed that sulcal measures were either superior than or equal to the other measures used for classification. Specifically, the g-SI and the width of the Sylvian fissure were two of the most sensitive sulcal measures and could be useful neuroanatomical markers for detecting early-stage AD. There were no significant differences between the three classifiers that we tested when using the same neuroanatomical features. PMID:28129351

  3. APOE genotype and neuroimaging markers of Alzheimer’s disease: systematic review and meta-analysis

    PubMed Central

    Liu, Ying; Yu, Jin-Tai; Wang, Hui-Fu; Han, Pei-Ran; Tan, Chen-Chen; Wang, Chong; Meng, Xiang-Fei; Risacher, Shannon L; Saykin, Andrew J

    2015-01-01

    Objective We aimed to examine the association of apolipoprotein E (APOE) ε4 genotype with neuroimaging markers of Alzheimer’s disease: hippocampal volume, brain amyloid deposition and cerebral metabolism. Methods We performed a systematic review and meta-analysis of 14 cross-sectional studies identified in Pubmed from 1996 to 2014 (n=1628). The pooled standard mean difference (SMD) was used to estimate the association between APOE and hippocampal volume and amyloid deposition. Meta-analysis was performed using effect size signed differential mapping using coordinates extracted from clusters with statistically significant difference in cerebral metabolic rate for glucose between APOE ε4+ and ε4− groups. Results APOE ε4 carrier status was associated with atrophic hippocampal volume (pooled SMD: −0.47; 95% CI −0.82 to −0.13; p=0.007) and increased cerebral amyloid positron emission tomography tracer (pooled SMD: 0.62, 95% CI 0.27 to 0.98, p=0.0006). APOE ε4 was also associated with decreased cerebral metabolism, especially in right middle frontal gyrus. Conclusions APOE ε4 was associated with atrophic hippocampal volume in MRI markers, increased cerebral amyloid deposition and cerebral hypometabolism. Theses associations may indicate the potential role of the APOE gene in the pathophysiology of Alzheimer’s disease. PMID:24838911

  4. Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques

    PubMed Central

    Sundman, Mark H; Hall, Eric E; Chen, Nan-kuei

    2014-01-01

    Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern. PMID:25324979

  5. Neuroimaging of major depression in Parkinson's disease: Cortical thickness, cortical and subcortical volume, and spectroscopy findings.

    PubMed

    Chagas, Marcos Hortes N; Tumas, Vitor; Pena-Pereira, Márcio A; Machado-de-Sousa, João Paulo; Carlos Dos Santos, Antonio; Sanches, Rafael Faria; Hallak, Jaime E C; Crippa, José Alexandre S

    2017-02-13

    Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group. Regarding cortical thickness, the left rostral anterior cingulate gyrus of the group with previous MDD was thinner compared to the control group. There was a weak negative correlation between the NAA/Cre ratio in the right putamen and depressive symptoms. The results suggested current and lifetime MDD have a negative impact on the neurodegenerative process of PD, with decreased volume and/or reduction of cortical thickness in temporal and frontal areas, anterior cingulate cortex, amygdala, and cerebellar white matter.

  6. Multivariate Data Analysis for Neuroimaging Data: Overview and Application to Alzheimer’s Disease

    PubMed Central

    Stern, Yaakov

    2010-01-01

    As clinical and cognitive neuroscience mature, the need for sophisticated neuroimaging analysis becomes more apparent. Multivariate analysis techniques have recently received increasing attention as they have many attractive features that cannot be easily realized by the more commonly used univariate, voxel-wise, techniques. Multivariate approaches evaluate correlation/covariance of activation across brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their results can be more easily interpreted as a signature of neural networks. Univariate approaches, on the other hand, cannot directly address functional connectivity in the brain. The covariance approach can also result in greater statistical power when compared with univariate techniques, which are forced to employ very stringent, and often overly conservative, corrections for voxel-wise multiple comparisons. Multivariate techniques also lend themselves much better to prospective application of results from the analysis of one dataset to entirely new datasets. Multivariate techniques are thus well placed to provide information about mean differences and correlations with behavior, similarly to univariate approaches, with potentially greater statistical power and better reproducibility checks. In contrast to these advantages is the high barrier of entry to the use of multivariate approaches, preventing more widespread application in the community. To the neuroscientist becoming familiar with multivariate analysis techniques, an initial survey of the field might present a bewildering variety of approaches that, although algorithmically similar, are presented with different emphases, typically by people with mathematics backgrounds. We believe that multivariate analysis techniques have sufficient potential to warrant better dissemination. Researchers should be able to employ them in an informed and accessible manner. The following article attempts to provide a basic introduction with sample

  7. Pseudotumoral hemicerebellitis as a mimicker of Lhermitte-Duclos disease in children: does neuroimaging help to differentiate them?

    PubMed

    Bosemani, Thangamadhan; Steinlin, Maja; Toelle, Sandra P; Beck, Jürgen; Boltshauser, Eugen; Huisman, Thierry A G M; Poretti, Andrea

    2016-05-01

    The clinical presentation and neuroimaging findings of children with pseudotumoral hemicerebellitis (PTHC) and Lhermitte-Duclos disease (LDD) may be very similar. The differentiation between these entities, however, is important because their management and prognosis are different. We report on three children with PTHC. For all three children, in the acute situation, the differentiation between PTHC and LDD was challenging. A review of the literature shows that a detailed evaluation of conventional and neuroimaging data may help to differentiate between these two entities. A striated folial pattern, brainstem involvement, and prominent veins surrounding the thickened cerebellar foliae on susceptibility weighted imaging favor LDD, while post-contrast enhancement and an increased choline peak on (1)H-Magnetic resonance spectroscopy suggest PTHC.

  8. Cognitive and neuroimaging profiles in mild cognitive impairment and Alzheimer's disease: data from the Spanish Multicenter Normative Studies (NEURONORMA Project).

    PubMed

    Sánchez-Benavides, Gonzalo; Peña-Casanova, Jordi; Casals-Coll, Marta; Gramunt, Nina; Molinuevo, José L; Gómez-Ansón, Beatriz; Aguilar, Miguel; Robles, Alfredo; Antúnez, Carmen; Martínez-Parra, Carlos; Frank-García, Anna; Fernández-Martínez, Manuel; Blesa, Rafael

    2014-01-01

    The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2-18) using co-normed reference values. Medians were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects.

  9. The clinical value of large neuroimaging data sets in Alzheimer's disease.

    PubMed

    Toga, Arthur W

    2012-02-01

    Rapid advances in neuroimaging and cyberinfrastructure technologies have brought explosive growth in the Web-based warehousing, availability, and accessibility of imaging data on a variety of neurodegenerative and neuropsychiatric disorders and conditions. There has been a prolific development and emergence of complex computational infrastructures that serve as repositories of databases and provide critical functionalities such as sophisticated image analysis algorithm pipelines and powerful three-dimensional visualization and statistical tools. The statistical and operational advantages of collaborative, distributed team science in the form of multisite consortia push this approach in a diverse range of population-based investigations.

  10. Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.

    PubMed

    Tan, Lin; Wang, Hui-Fu; Tan, Meng-Shan; Tan, Chen-Chen; Zhu, Xi-Chen; Miao, Dan; Yu, Wan-Jiang; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2016-05-27

    The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD.

  11. Data sharing in neuroimaging research

    PubMed Central

    Poline, Jean-Baptiste; Breeze, Janis L.; Ghosh, Satrajit; Gorgolewski, Krzysztof; Halchenko, Yaroslav O.; Hanke, Michael; Haselgrove, Christian; Helmer, Karl G.; Keator, David B.; Marcus, Daniel S.; Poldrack, Russell A.; Schwartz, Yannick; Ashburner, John; Kennedy, David N.

    2012-01-01

    Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging. PMID:22493576

  12. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

    PubMed

    Ye, Zheng; Rae, Charlotte L; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle-Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R; Maxwell, Helen; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-03-01

    Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features.

  13. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

    PubMed Central

    Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037

  14. Alterations of Myelin Content in Parkinson’s Disease: A Cross-Sectional Neuroimaging Study

    PubMed Central

    Sojkova, Jitka; Hurley, Samuel; Kecskemeti, Steven; Okonkwo, Ozioma; Bendlin, Barbara B.; Theisen, Frances; Johnson, Sterling C.; Alexander, Andrew L.; Gallagher, Catherine L.

    2016-01-01

    Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain’s myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson’s disease. PMID:27706215

  15. Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease

    PubMed Central

    Grossman, M.; Payer, F.; Onishi, K.; White-Devine, T.; Morrison, D.; D'Esposito, M.; Robinson, K.; Alavi, A.

    1997-01-01

    OBJECTIVE—Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing.
METHODS—Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group.
RESULTS—Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing.
CONCLUSION—These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

 PMID:9285450

  16. Recent advances in biomarkers for Parkinson's disease focusing on biochemicals, omics and neuroimaging.

    PubMed

    Ren, Rutong; Sun, Yi; Zhao, Xin; Pu, Xiaoping

    2015-09-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, involving progressive loss of the nigro-striatal dopaminergic neurons. Cardinal symptoms including tremors, muscle rigidity, drooping posture, drooping, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons have already been destroyed. Hence, reliable biomarkers are needed for early and accurate diagnosis to measure disease progression and response to therapy. We review the current status of protein and small molecule biomarkers involved in oxidative stress, protein aggregation and inflammation etc. which are present in cerebrospinal fluid, human blood, urine or saliva. In recent years, advances in genomics, proteomics, metabolomics, and functional brain imaging techniques have led to new insights into the pathoetiology of PD. Further studies in the novel discovery of PD biomarkers will provide avenues to treat PD patients more effectively with few or no side effects.

  17. Clinical, genetic, and neuroimaging features of Early Onset Alzheimer Disease: the challenges of diagnosis and treatment.

    PubMed

    Alberici, Antonella; Benussi, Alberto; Premi, Enrico; Borroni, Barbara; Padovani, Alessandro

    2014-01-01

    Early Onset Alzheimer Disease (EOAD) is a rare condition, frequently associated with genetic causes. The dissemination of genetic testing along with biomarker determinations have prompted a wider recognition of EOAD in experienced clinical settings. However, despite the great efforts in establishing the contribution of causative genes to EOAD, atypical disease presentation and clinical features still makes its diagnosis and treatment a challenge for the clinicians. This review aims to provide an extensive evaluation of literature data on EOAD, in order to improve understanding and knowledge of EOAD, underscore its significant impact on patients and their caregivers and influence public policies. This would be crucial to define the urgency of evidence-based treatment approaches.

  18. A Pilot Study on Clinical and Neuroimaging Characteristics of Chinese Posterior Cortical Atrophy: Comparison with Typical Alzheimer’s Disease

    PubMed Central

    Shi, Zhihong; Cai, Li; Liu, Shuai; Liu, Shuling; Han, Tong; Wang, Ying; Zhou, Yuying; Wang, Xinping; Gao, Shuo; Ji, Yong

    2015-01-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer’s disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer’s disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11C-PIB PET scan and 18F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings. PMID:26267071

  19. The Southern Cone Initiative against Chagas disease.

    PubMed

    Schofield, C J; Dias, J C

    1999-01-01

    Chagas disease (also known as American trypanosomiasis) is now ranked as the most serious parasitic disease of the Americas, with an economic impact far outranking the combined effects of other parasitic diseases such as malaria, schistosomiasis and leishmaniasis. Although the chronic infection remains virtually incurable, transmission can be halted by eliminating the domestic insect vectors and screening blood donors to avoid transfusional transmission. In line with this strategy, governments of the six Southern Cone countries (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay) launched in 1991 an ambitious initiative to control Chagas disease through elimination of the main vector, Triatoma infestans, and large-scale screening of blood donors. Now at its mid-point, the programme has achieved remarkable success, with transmission halted over vast areas of the previously endemic regions. Well over 2 million rural houses have been sprayed to eliminate T. infestans, and the programme has already shown significant economic rates of return in addition to the medical and social benefits.

  20. Cholinesterase inhibitors are compatible with psychosocial intervention for Alzheimer disease patients suggested by neuroimaging findings.

    PubMed

    Meguro, Kenichi

    2017-01-30

    We previously reported that the frontal lobe was stimulated by psychosocial intervention for dementia patients, and that the parietal lobe was associated with logical judgment. We hypothesized that the combined therapeutic approach with symptomatic drug treatment can directly stimulate not only attention function but also judgment function indirectly to observing other participants' behaviors. Fifty-two patients with Alzheimer disease underwent the group reminiscence approach with reality orientation, as well as the donepezil treatment. The cerebral blood flow (CBF) was assessed with (99m)Tc-ECD SPECT. Two analyses were performed: Analysis 1 was to compare Responders vs. Non-responders as shown by MMSE scores, whereas Analysis 2 was to compare Good vs. Poor reminders of the intervention content. We found that the CBF in the frontal lobe was significantly higher in Responders (vs. Non-responders). The CBF in the parietal lobe, especially the left side, was significantly higher in the Good reminders (vs. Poor reminders). The donepezil stimulated the areas similar to where the psychosocial intervention was previously found to be stimulated directly, thus the drug was thought to be compatible for psychosocial intervention. The parietal lobe was stimulated indirectly, suggesting that the indirect effect of the intervention may be based on logical judgment function.

  1. Neuroimaging tools to rate regional atrophy, subcortical cerebrovascular disease, and regional cerebral blood flow and metabolism: consensus paper of the EADC

    PubMed Central

    Frisoni, G; Scheltens, P; Galluzzi, S; Nobili, F; Fox, N; Robert, P; Soininen, H; Wahlund, L; Waldemar, G; Salmon, E

    2003-01-01

    Neuroimaging is a mainstay in the differential diagnosis of patients with cognitive impairment. The often equivocal clinical pictures, the prognostic uncertainty of the earliest stages of mild cognitive impairment, and the subtle brain changes mean that neuroimaging techniques are of potentially great incremental diagnostic value. A number of methods, ranging from very simple subjective visual ratings to highly sophisticated computerised tools, have been developed, which allow rating of structural and functional brain changes. The choice of the method is not obvious, and current guidelines provide no indications on which tools should be preferred. In this paper, we give indications for tools with demonstrated accuracy for detecting regional atrophy, cerebrovascular disease, and regional brain function, and discuss these according to increasing technological complexity, ranging from those with high feasibility that can be used at the patient's bedside to highly technological ones that require trained personnel and specific hardware and software. PMID:14570828

  2. Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson’s Disease with Dementia and Dementia with Lewy Bodies

    PubMed Central

    Takemoto, Mami; Sato, Kota; Hatanaka, Noriko; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-01-01

    Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in “orientation to place” tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99mTc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients’ lower average scores for “repetition” (MMSE), “recent memory” (HDS-R), and “lexical fluency” (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients’ poorer average subscale scores of “orientation to place” (MMSE) and “similarities”, “conflicting instructions”, and “go-no go” (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD. PMID:27060948

  3. Typical and atypical appearance of early-onset Alzheimer's disease: A clinical, neuroimaging and neuropathological study.

    PubMed

    Kawakatsu, Shinobu; Kobayashi, Ryota; Hayashi, Hiroshi

    2017-04-01

    The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia. We reported MRI, single-photon emission CT and neuropathological findings in six representative cases. We also described a "left temporal variant" of AD presenting with transcortical cortical sensory aphasia, which has not been reported previously and is another subtype of the posterior variant of AD. We found a significant correlation between regional cerebral blood flow and counts of NFTs in the cerebral cortices. An atypical presentation with focal neuropsychological symptoms roughly correlated with the density of NFTs in the cerebral cortex and more directly related to spongiform changes in the superficial layers of these areas. In contrast, the distribution of amyloid depositions was diffuse and did not necessarily correlate with focal neuropsychological symptoms. Braak staging or ABC score is not necessarily appropriate to evaluate atypical AD, and instead, spongiform changes in addition to tau pathology in the association cortices better explain the diversity of atypical AD. Interestingly, another patient with a posterior variant of AD had a novel type of atypical plaque, which we referred to as "lucent plaque". They were recognizable with HE staining in the circumference and dystrophic neurites were abundant with Gallyas-Braak staining. These plaques demonstrated intense immunoreactivity to both tau AT-8 and amyloid β (Aβ), suggesting a peculiar coexistence pattern of amyloid and tau in these plaques. Clinicopathological studies

  4. Neuroimaging over the course of Parkinson's disease: from early detection of the at-risk patient to improving pharmacotherapy of later-stage disease.

    PubMed

    Seibyl, John; Russell, David; Jennings, Danna; Marek, Kenneth

    2012-11-01

    Brain imaging of striatal dopamine terminal degeneration serves an important role in the clinical management of Parkinson's disease (PD). Imaging biomarkers for interrogating dopaminergic systems are used for clarifying diagnosis when only subtle motor symptoms are present. However, motor dysfunction is not the earliest symptom of PD. There is increasing interest in identifying premotor PD patients, particularly because potential disease-modifying therapies are developed and the clinical imperative becomes early and accurate diagnosis. On the other end of the spectrum of the disease course, during later stages of PD, significant clinical challenges like levo-dopa-induced dyskinesias and medication on-off phenomenon become more prevalent. In this instance, better understanding of altered PD motor pathways suggests the potential utility of novel treatments targeting neuronal systems that are impacted by degenerating dopamine neurons and chronic dopamine replacement treatment. Molecular neuroimaging serves unique roles in both very early PD and later-stage disease, in the former, potentially pushing back the time of diagnosis, and in the latter, elucidating pathology relevant to new drug development.

  5. The Co-evolution of Neuroimaging and Psychiatric Neurosurgery

    PubMed Central

    Dyster, Timothy G.; Mikell, Charles B.; Sheth, Sameer A.

    2016-01-01

    The role of neuroimaging in psychiatric neurosurgery has evolved significantly throughout the field’s history. Psychiatric neurosurgery initially developed without the benefit of information provided by modern imaging modalities, and thus lesion targets were selected based on contemporary theories of frontal lobe dysfunction in psychiatric disease. However, by the end of the 20th century, the availability of structural and functional magnetic resonance imaging (fMRI) allowed for the development of mechanistic theories attempting to explain the anatamofunctional basis of these disorders, as well as the efficacy of stereotactic neuromodulatory treatments. Neuroimaging now plays a central and ever-expanding role in the neurosurgical management of psychiatric disorders, by influencing the determination of surgical candidates, allowing individualized surgical targeting and planning, and identifying network-level changes in the brain following surgery. In this review, we aim to describe the coevolution of psychiatric neurosurgery and neuroimaging, including ways in which neuroimaging has proved useful in elucidating the therapeutic mechanisms of neuromodulatory procedures. We focus on ablative over stimulation-based procedures given their historical precedence and the greater opportunity they afford for post-operative re-imaging, but also discuss important contributions from the deep brain stimulation (DBS) literature. We conclude with a discussion of how neuroimaging will transition the field of psychiatric neurosurgery into the era of precision medicine. PMID:27445706

  6. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer’s disease patients at an early disease stage

    PubMed Central

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer’s disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  7. Clinical neuroimaging

    SciTech Connect

    Gilman, S.; Mazziotta, J.C.

    1989-01-01

    Designed for practicing neurologists and neurosurgeons, this reference focuses on the newest techniques in computed assisted tomography. Text material covers basic principles of computed tomography, as well as the clinical advantages and disadvantages of each modality. The anatomical and/or physiological processes measured by XCT, PET, SPECT and MRI are first discussed in terms of the normal patient, and then applied to the diagnosis and treatment of patients with neurological disease (primarily of the brain). Emphasis is placed on areas of difficult diagnosis, such as differentiating recurrent tumor from radiation necrosis, early diagnosis of dementia, selection of patients for extracranial-intracranial bypass procedures, and localization of epileptic foci.

  8. Initial Staging of Hodgkin’s Disease

    PubMed Central

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-01-01

    Abstract The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD). Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard. No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor). Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID:25121354

  9. Structural brain network constrained neuroimaging marker identification for predicting cognitive functions.

    PubMed

    De, Wang; Nie, Feiping; Huang, Heng; Yan, Jingwen; Risacher, Shannon L; Saykin, Andrew J; Shen, Li

    2013-01-01

    Neuroimaging markers have been widely used to predict the cognitive functions relevant to the progression of Alzheimer's disease (AD). Most previous studies identify the imaging markers without considering the brain structural correlations between neuroimaging measures. However, many neuroimaging markers interrelate and work together to reveal the cognitive functions, such that these relevant markers should be selected together as the phenotypic markers. To solve this problem, in this paper, we propose a novel network constrained feature selection (NCFS) model to identify the neuroimaging markers guided by the structural brain network, which is constructed by the sparse representation method such that the interrelations between neuroimaging features are encoded into probabilities. Our new methods are evaluated by the MRI and AV45-PET data from ADNI-GO and ADNI-2 (Alzheimer's Disease Neuroimaging Initiative). In all cognitive function prediction tasks, our new NCFS method outperforms other state-of-the-art regression approaches. Meanwhile, we show that the new method can select the correlated imaging markers, which are ignored by the competing approaches.

  10. Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

    PubMed Central

    Albaugh, Daniel L.

    2014-01-01

    Abstract Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) represents a powerful clinical tool for the alleviation of many motor symptoms that are associated with Parkinson's disease. Despite its extensive use, the underlying therapeutic mechanisms of STN-DBS remain poorly understood. In the present review, we integrate and discuss recent literature examining the network effects of STN-DBS for Parkinson's disease, placing emphasis on neuroimaging findings, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These techniques enable the noninvasive detection of brain regions that are modulated by DBS on a whole-brain scale, representing a key experimental strength given the diffuse and far-reaching effects of electrical field stimulation. By examining these data in the context of multiple hypotheses of DBS action, generally developed through clinical and physiological observations, we define a multitude of consistencies and inconsistencies in the developing literature of this rapidly moving field. PMID:24147633

  11. Functional Neuroimaging: A Physiological Perspective

    PubMed Central

    Lin, Ai-Ling; Gao, Jia-Hong; Duong, Timonthy Q.; Fox, Peter T.

    2010-01-01

    Metabolic physiology and functional neuroimaging have played important and complementary roles over the past two decades. In particular, investigations of the mechanisms underlying functional neuroimaging signals have produced fundamental new insights into hemodynamic and metabolic regulation. However, controversies were also raised as regards the metabolic pathways (oxidative vs. non-oxidative) for meeting the energy demand and driving the increases in cerebral blood flow (CBF) during brain activation. In a recent study, with the concurrent functional MRI-MRS measurements, we found that task-evoked energy demand was predominately met through oxidative metabolism (approximately 98%), despite a small increase in cerebral metabolic rate of oxygen (12–17%). In addition, the task-induced increases in CBF were most likely mediated by anaerobic glycolysis rather than oxygen demand. These observations and others from functional neuroimaging support the activation-induced neuron-astrocyte interactions portrayed by the astrocyte-neuron lactate shuttle model. The concurrent developments of neuroimaging methods and metabolic physiology will also pave the way for the future investigation of cerebral hemodynamics and metabolism in disease states. PMID:20725632

  12. Parkinson's disease: initial treatment of motor disorders.

    PubMed

    2015-09-01

    Parkinson's disease is characterised by three main symptoms: slowness and paucity of movements, rigidity, and resting tremor. Rapid improvement in these symptoms after levodopa administration supports the diagnosis of Parkinson's disease. It is important to inform the patient tactfully, allowing him or her to control the pace at which information on the diagnosis, symptoms and prognosis is conveyed. Patients with minimal discomfort or mild disability derive little benefit from drug therapy. Physiotherapy and physical exercises are sometimes useful. Previously untreated patients with marked functional impairment should receive medication. The choice is essentially between levodopa and ropinirole, and mainly depends on the patient's age.

  13. Neuroimaging of epilepsy

    PubMed Central

    Cendes, Fernando; Theodore, William H.; Brinkmann, Benjamin H.; Sulc, Vlastimil; Cascino, Gregory D.

    2017-01-01

    Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454

  14. Neuroimaging in Cockayne syndrome.

    PubMed

    Koob, M; Laugel, V; Durand, M; Fothergill, H; Dalloz, C; Sauvanaud, F; Dollfus, H; Namer, I J; Dietemann, J-L

    2010-10-01

    CS is an autosomal recessive multisystem disorder, which is mainly characterized by neurologic and sensory impairment, cachectic dwarfism, and photosensitivity. We describe the neuroimaging features (MR imaging, ¹H-MR spectroscopy, and CT) in the various clinical subtypes of CS from a cohort of genetically and biochemically proved cases. Hypomyelination, calcifications, and brain atrophy were the main imaging features. Calcifications were typically found in the putamen and less often in the cortex and dentate nuclei. Severe progressive atrophy was seen in the supratentorial white matter, the cerebellum, the corpus callosum, and the brain stem. Patients with early-onset disease displayed more severe hypomyelination and prominent calcifications in the sulcal depth of the cerebral cortex, but atrophy was less severe in late-onset patients. On proton MR spectroscopy, lactate was detected and Cho and NAA values were decreased. These combined neuroradiologic findings can help in the differential diagnosis of CS, distinguishing it from other leukoencephalopathies and/or cerebral calcifications in childhood.

  15. Functional neuroimaging in psychiatry.

    PubMed Central

    Fu, C H; McGuire, P K

    1999-01-01

    Functional neuroimaging is one of the most powerful means available for investigating the pathophysiology of psychiatric disorders. In this review, we shall focus on the different ways that it can be employed to this end, describing the major findings in the field in the context of different methodological approaches. We will also discuss practical issues that are particular to studying psychiatric disorders and the potential contribution of functional neuroimaging to future psychiatric research. PMID:10466156

  16. Human neuroimaging as a "Big Data" science.

    PubMed

    Van Horn, John Darrell; Toga, Arthur W

    2014-06-01

    The maturation of in vivo neuroimaging has led to incredible quantities of digital information about the human brain. While much is made of the data deluge in science, neuroimaging represents the leading edge of this onslaught of "big data". A range of neuroimaging databasing approaches has streamlined the transmission, storage, and dissemination of data from such brain imaging studies. Yet few, if any, common solutions exist to support the science of neuroimaging. In this article, we discuss how modern neuroimaging research represents a multifactorial and broad ranging data challenge, involving the growing size of the data being acquired; sociological and logistical sharing issues; infrastructural challenges for multi-site, multi-datatype archiving; and the means by which to explore and mine these data. As neuroimaging advances further, e.g. aging, genetics, and age-related disease, new vision is needed to manage and process this information while marshalling of these resources into novel results. Thus, "big data" can become "big" brain science.

  17. The Road Ahead to Cure Alzheimer’s Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations

    PubMed Central

    Cavedo, E.; Lista, S.; Khachaturian, Z.; Aisen, P.; Amouyel, P.; Herholz, K.; Jack, C.R.; Sperling, R.; Cummings, J.; Blennow, K.; O’Bryant, S.; Frisoni, G.B.; Khachaturian, A.; Kivipelto, M.; Klunk, W.; Broich, K.; Andrieu, S.; de Schotten, M. Thiebaut; Mangin, J.-F.; Lammertsma, A.A.; Johnson, K.; Teipel, S.; Drzezga, A.; Bokde, A.; Colliot, O.; Bakardjian, H.; Zetterberg, H.; Dubois, B.; Vellas, B.; Schneider, L.S.; Hampel, H.

    2015-01-01

    Alzheimer’s disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group’s revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard (“core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and “mild cognitive impairment due to AD” include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis

  18. Familial Creutzfeldt-Jakob disease with the E200K mutation: longitudinal neuroimaging from asymptomatic to symptomatic CJD.

    PubMed

    Cohen, Oren S; Chapman, Joab; Korczyn, Amos D; Nitsan, Zeev; Appel, Shmuel; Hoffmann, Chen; Rosenmann, Hanna; Kahana, Esther; Lee, Hedok

    2015-03-01

    Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. While carriers are born with this mutation, they usually remain asymptomatic until middle age. Early detection of conversion is crucial for understanding and eventually for the treatment of the disease. The aim of this study was to report longitudinal MRI data in E200K individuals who eventually converted from healthy mutation carriers to clinically symptomatic CJD. As a part of a prospective study, asymptomatic E200K mutation carriers were scanned annually until their conversion to symptomatic disease. Standardized diffusion and anatomical MR sequences were performed before and after clinical conversion in the subjects and those were compared to 15 non-carrier siblings ("healthy controls"). Blinded radiological readings and region of interest analyses were performed. Radiological readings of individual cases failed to detect characteristic changes in the scans taken before the conversion. Region of interest analysis of diffusion changes in pre-symptomatic stage was inconclusive; however, ADC reduction was found in early and late stages of the disease. Computerized volumetric analysis revealed monotonic volume reductions in thalamus, putamen and caudate following conversion, and the lateral ventricles showed dilatation of up to 62 % after clinical conversion. Although the clinical manifestations at disease onset are variable, the diffusion abnormalities and/or volume changes in the thalamus and basal ganglia during conversion may indicate early involvement of the thalamostriatal neuronal circuit.

  19. A review of neuroimaging studies of stressor-evoked blood pressure reactivity: Emerging evidence for a brain-body pathway to coronary heart disease risk

    PubMed Central

    Gianaros, Peter J.; Sheu, Lei K.

    2009-01-01

    An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the ‘brain-body’ pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala—as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the ‘brain-body’ pathways that mechanistically link stressful experiences with CHD risk. PMID:19410652

  20. Computer-assisted initial diagnosis of rare diseases

    PubMed Central

    Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

  1. Computer-assisted initial diagnosis of rare diseases.

    PubMed

    Alves, Rui; Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient's symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.

  2. Exploring yawning with neuroimaging.

    PubMed

    Nahab, Fatta B

    2010-01-01

    The neural mechanisms responsible for spontaneous yawning as well as contagious yawning are not well characterized. Neuroimaging is an essential tool for helping to identify the seminal neural structures and their inter-related functions to carry out this complex stereotyped motor program. Studies to date have explored the structural neural correlates of yawning through a series of lesion-based case reports and identified participatory structures at various levels of the central nervous system. Functional neuroimaging methods like fMRI have also shed led on the genesis of contagious yawning, though cohesive models explaining the neural mechanisms of contagious motor programs such as yawning remain limited.

  3. Neuroimaging and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

  4. Neuroimaging and Psychopharmacology

    ERIC Educational Resources Information Center

    Semrud-Clikeman, Margaret; Pliszka, Steve R.

    2005-01-01

    This review presents the most recent research concerning neuroimaging in developmental disabilities. Changes in structure and activation have been found in children with ADHD and learning disabilities, following intervention. For the children with learning disabilities changes in activation have been found following intensive behavioral and…

  5. Introduction to neuroimaging

    SciTech Connect

    Orrison, W.W.

    1989-01-01

    The author focuses on neuroradiology with emphasis on the current imaging modalities. There are chapters on angiography, myelography, nuclear medicine, ultrasonography, computer tomography (CT), and magnetic resonance (MR) imaging. The other chapters are dedicated to the spine, skull, head and neck, and pediatric neuroimaging.

  6. Neuroimaging and Aggression.

    ERIC Educational Resources Information Center

    Mills, Shari; Raine, Adrian

    1994-01-01

    Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

  7. Neuroimaging and Fetal Alcohol Spectrum Disorders

    PubMed Central

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2012-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and central nervous system (CNS) disorganization, with specific structural abnormalities of the corpus callosum, cerebellum, caudate, and hippocampus. Advances in neuroimaging techniques have allowed detection of regional increases in cortical thickness and gray matter volume along with decreased volume and disorganization of white matter in individuals with FASD. In addition, functional imaging studies have found functional and neurochemical differences in those prenatally exposed to alcohol. Behavioral alterations noted in individuals with FASD are consistent with the findings noted in the brain imaging studies. Continued neuroimaging studies are needed to further advance understanding of the neuroteratogenic effects of alcohol. PMID:19731391

  8. The Relationship Between Parkinson's Disease and Essential Tremor: Review of Clinical, Epidemiologic, Genetic, Neuroimaging and Neuropathological Data, and Data on the Presence of Cardinal Signs of Parkinsonism in Essential Tremor

    PubMed Central

    Jiménez-Jiménez, Félix Javier; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

    2012-01-01

    Background The possible relationship between essential tremor (ET) and Parkinson's disease (PD) has been controversial since the first description of PD. However, there is increasing evidence suggesting an overlap between these two disorders. The aim of this review is to examine the relationship between PD and ET, focusing on clinical, epidemiologic, genetic, neuroimaging, and neuropathological data, and the presence of cardinal parkinsonism symptoms in ET. Methods We conducted a PubMed search for articles published between 1966 and November 2011 regarding the relationship between ET and PD and the presence of postural tremor in PD patients; the presence of rest tremor, rigidity, and slowed movements in ET patients is reviewed. Results Clinical series, follow-up studies of ET patients, and case–control and genetic epidemiological studies indicate that ET is associated with increased risk for PD. Some neuroimaging studies and neuropathological reports suggest an association between the two diseases. ET patients show high prevalence of rest tremor, and at least seven studies described slowed movements (possibly related to cerebellar dysfunction and/or bradykinesia) in patients with ET. Discussion There is reasonable epidemiological and clinical evidence to support a link between ET and PD, although it is not clear what factors predict ET patient risk for developing PD or, more rarely, of PD patients developing ET. Future multicentric and multidisciplinary studies including epidemiological, clinical, neuroimaging, genetic, and neuropathological assessments are required to understand these associations. PMID:23439992

  9. Development of Alzheimer-disease neuroimaging-biomarkers using mouse models with amyloid-precursor protein-transgene expression.

    PubMed

    Teipel, Stefan J; Buchert, Ralph; Thome, Johannes; Hampel, Harald; Pahnke, Jens

    2011-12-01

    There are important recent developments in Alzheimer's disease (AD) translational research, especially with respect to the imaging of amyloid pathology in vivo using MRI and PET technologies. Here we exploit the most widely used transgenic mouse models of amyloid pathology in order to relate the imaging findings to our knowledge about the histopathological phenotype of these models. The development of new diagnostic criteria of AD necessitates the use of biological markers to diagnose AD even in the absence of overt dementia or early symptomatic mild cognitive impairment. The validity of the diagnosis will depend on the availability of an in vivo marker to reflect underlying neurobiological changes of AD. Transgenic models with essential features of AD pathology and mechanisms provide a test setting for the development and evaluation of new biological imaging markers. Among the best established imaging markers of amyloid pathology in transgenic animals are high-field MRI of brain atrophy, proton spectroscopy of neurochemical changes, high-field MRI of amyloid plaque load, and in vivo plaque imaging using radio-labelled ligands with PET. We discuss the implications of the findings as well as the methodological limitations and the specific requirements of these technologies. We furthermore outline future directions of transgene-imaging research. Transgene imaging is an emerging area of translational research that implies strong multi- and interdisciplinary collaborations. It will become ever more valuable with the introduction of new diagnostic standards and novel treatment approaches which will require valid and reliable biological markers to improve the diagnosis and early treatment of AD patients.

  10. Longitudinal change of neuroimaging and clinical markers in autosomal dominant Alzheimer’s disease: a prospective cohort study

    PubMed Central

    Yau, Wai-Ying Wendy; Tudorascu, Dana L.; McDade, Eric M.; Ikonomovic, Snezana; James, Jeffrey A.; Minhas, Davneet; Mowrey, Wenzhu; Sheu, Lei K.; Snitz, Beth E.; Weissfeld, Lisa; Gianaros, Peter J.; Aizenstein, Howard J.; Price, Julie C.; Mathis, Chester A.; Lopez, Oscar L.; Klunk, William E.

    2015-01-01

    Background The biomarker model of Alzheimer’s disease (AD) hypothesizes a dynamic sequence of amyloidosis, neurodegeneration, and cognitive decline, as an individual progresses from preclinical AD to dementia. Despite supportive evidence from cross-sectional studies, verification with long-term within-individual data is needed. Methods Autosomal dominant AD (ADAD) mutation carriers, aged 21 years or older (no cognitive restrictions), were recruited from across the United States via referral by colleagues or ADAD families themselves. Sixteen individuals with mutations in PSEN1, PSEN2 or APP, aged 28 to 56, were assessed longitudinally every one to two years, between March 23, 2003 and August 1, 2014. Participants completed two to eight assessments (total=83), over a period of two to eleven years. We measured global amyloid-beta load with Pittsburgh Compound-B PET, posterior cortical metabolism with [18F]fluorodeoxyglucose PET, hippocampal volume (age-, and gender-corrected) with T1 MRI, verbal memory with 10-item delayed word recall, and general cognition with Mini Mental State Exam. We estimated overall biomarker trajectories across estimated years from symptom onset (EYO) using linear mixed models, and compared ADAD estimates to cross-sectional data from cognitively normal, older controls selected to be negative for amyloidosis, hypometabolism, and hippocampal atrophy. In seven individuals with the longest follow-up (seven/eight assessments spanning six to eleven years), we further examined the within-individual progression of amyloidosis, metabolism, hippocampal volume, and cognition, to identify progressive within-individual change in these markers (increase/decrease of greater than two Z-scores standardized to controls). Findings Significant differences in ADAD compared to controls (p<0·01) were detected in the following order: increased amyloidosis (−7.5 EYO), decreased metabolism (0 EYO), decreased hippocampal volume and verbal memory (+7.5 EYO

  11. Neuroimaging in anxiety disorders.

    PubMed

    Engel, Kirsten; Bandelow, Borwin; Gruber, Oliver; Wedekind, Dirk

    2009-06-01

    Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, "normal anxiety" does not equal "pathological anxiety" although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors.

  12. Excessive blinking as an initial manifestation of juvenile Huntington's disease.

    PubMed

    Xing, Shihui; Chen, Ling; Chen, Xi; Pei, Zhong; Zeng, Jinsheng; Li, Jinru

    2008-09-01

    Juvenile Huntington's disease (JHD) is mostly characterized by rigidity, myoclonus, bradykinesia, dystonia and seizure. We report a 9-year-old male JHD patient presenting excessive blinking as the initial symptom two years prior to typical JHD symptoms. Genetic analysis revealed expansion of 108 CAG repeats and magnetic resonance imaging showed caudate atrophy with lateral ventricular enlargement.

  13. Psychotherapy and Neuroimaging

    PubMed Central

    Fournier, Jay C.; Price, Rebecca B.

    2014-01-01

    Technological advances in neuroimaging have enabled researchers to examine, in vivo, the relationship between psychotherapeutic interventions and markers of brain activity. This review focuses on two kinds of neuroimaging studies in psychotherapy: those that examine the patterns of brain activity associated with response to treatments and those that examine the changes that occur in brain activity during treatment. A general, hypothetical neural model of psychotherapy is presented, and support for the model is evaluated across anxiety disorders and major depression. Neuroimaging studies are broadly consistent in observing associations between response to psychotherapy and baseline activity in several key regions within the prefrontal cortex, basal ganglia, and limbic areas. These regions are involved in the generation and regulation of emotion, fear responding, and response to reward. Pre-post examinations of change following psychotherapy also typically observe that psychological treatments for anxiety and depression can affect neural activity in these regions. Despite general consensus that activity in these regions is associated with psychotherapy, substantial discrepancy persists regarding the precise direction of the observed relationships. Methodological challenges of the existing literature are considered, and future directions are discussed. PMID:25346646

  14. Retrospective study on structural neuroimaging in first-episode psychosis

    PubMed Central

    Silva-dos-Santos, Amilcar; Talina, Miguel Cotrim

    2016-01-01

    Background. No consensus between guidelines exists regarding neuroimaging in first-episode psychosis. The purpose of this study is to assess anomalies found in structural neuroimaging exams (brain computed tomography (CT) and magnetic resonance imaging (MRI)) in the initial medical work-up of patients presenting first-episode psychosis. Methods. The study subjects were 32 patients aged 18–48 years (mean age: 29.6 years), consecutively admitted with first-episode psychosis diagnosis. Socio-demographic and clinical data and neuroimaging exams (CT and MRI) were retrospectively studied. Diagnostic assessments were made using the Operational Criteria Checklist +. Neuroimaging images (CT and MRI) and respective reports were analysed by an experienced consultant psychiatrist. Results. None of the patients had abnormalities in neuroimaging exams responsible for psychotic symptoms. Thirty-seven percent of patients had incidental brain findings not causally related to the psychosis (brain atrophy, arachnoid cyst, asymmetric lateral ventricles, dilated lateral ventricles, plagiocephaly and falx cerebri calcification). No further medical referral was needed for any of these patients. No significant differences regarding gender, age, diagnosis, duration of untreated psychosis, in-stay and cannabis use were found between patients who had neuroimaging abnormalities versus those without. Discussion. This study suggests that structural neuroimaging exams reveal scarce abnormalities in young patients with first-episode psychosis. Structural neuroimaging is especially useful in first-episode psychosis patients with neurological symptoms, atypical clinical picture and old age. PMID:27257547

  15. Initiation of acute graft-versus-host disease by angiogenesis.

    PubMed

    Riesner, Katarina; Shi, Yu; Jacobi, Angela; Kraeter, Martin; Kalupa, Martina; McGearey, Aleixandria; Mertlitz, Sarah; Cordes, Steffen; Schrezenmeier, Jens-Florian; Mengwasser, Jörg; Westphal, Sabine; Perez-Hernandez, Daniel; Schmitt, Clemens; Dittmar, Gunnar; Guck, Jochen; Penack, Olaf

    2017-01-17

    The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes. However, it is not known if angiogenesis has an active role during the initiation of inflammation or if it is merely a secondary effect occurring in response to stimuli by tissue infiltrating leukocytes. Here we show that angiogenesis precedes leukocyte infiltration in experimental models of inflammatory bowel disease and acute graft-versus-host disease (GVHD). We found that angiogenesis occurred as early as day+2 after allogeneic transplantation mainly in GVHD typical target organs skin, liver and intestines whereas no angiogenic changes appeared due to conditioning or syngeneic transplantation. The initiation phase of angiogenesis was not associated to classical endothelial cell (EC) activation signs, such as Vegfa/VEGFR1+2 upregulation or increased adhesion molecule expression. During early GVHD at day+2, we found significant metabolic and cytoskeleton changes in target organ ECs in gene array- and proteomic analyses. These modifications have significant functional consequences as indicated by profoundly higher deformation in Real-time deformability cytometry. Our results demonstrate that metabolic changes trigger alterations in cell mechanics leading to enhanced migratory and proliferative potential of ECs during the initiation of inflammation. Our study adds evidence to the hypothesis that angiogenesis is involved in the initiation of tissue inflammation during GVHD.

  16. A probabilistic functional atlas of the VIM nucleus constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients.

    PubMed

    Nowinski, Wieslaw L; Belov, Dmitry; Thirunavuukarasuu, A; Benabid, Alim Louis

    2005-01-01

    We have previously introduced a concept of a probabilistic functional atlas (PFA) to overcome limitations of the current electronic stereotactic brain atlases: anatomical nature, spatial sparseness, inconsistency and lack of population information. The PFA for the STN has already been developed. This work addresses construction of the PFA for the ventrointermediate nucleus (PFA-VIM). The PFA-VIM is constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients. The data contain the positions of the chronically implanted electrodes and their best contacts. For each patient, the intercommissural distance, height of the thalamus and width of the third ventricle were measured. An algorithm was developed to convert these data into the PFA-VIM, and to present them on axial, coronal and sagittal planes and in 3-D. The PFA-VIM gives a spatial distribution of the best contacts, and its probability is proportional to best contact concentration in a given location. The region with the highest probability corresponds to the best target. The PFA-VIM is calculated with 0.25-mm3 resolution from 107 best contacts in two situations: with and without lateral compensation against the width of the third ventricle. For the PFA-VIM compensated laterally, the anterior, lateral and dorsal coordinates of the mean value are (in mm) 6.24, 13.83, 1.68 for the left VIM and 6.54, -13.84, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts (P) are: 6.25, 14.25, 1.75, P = 16, for the left VIM, and 6.0, -14.0, 1.00, P = 18, for the right VIM. The coordinate system origin is at the posterior commissure. For the PFA-VIM not compensated laterally, the coordinates of the mean value are 6.24, 13.99, 1.68 for the left VIM and 6.53, -14.13, 2.10 for the right VIM. The coordinates of the mean value of the highest

  17. Giardia and Cryptosporidium join the 'Neglected Diseases Initiative'.

    PubMed

    Savioli, L; Smith, H; Thompson, A

    2006-05-01

    Giardia and Cryptosporidium are ubiquitous enteric protozoan pathogens that infect humans, domestic animals and wildlife worldwide. Both pathogens are significant causes of diarrhea and nutritional disorders in institutional and community settings. They are also significant waterborne pathogens. In developing regions of the world, Giardia and Cryptosporidium constitute part of the complex group of parasitic, bacterial and viral diseases that impair the ability to achieve full potential and impair development and socio-economic improvements. All diseases included in the WHO Neglected Diseases Initiative have a common link with poverty and, as the current view is to take a comprehensive approach to all these diseases, both Giardia and Cryptosporidium were included in 2004. Our current state of knowledge of Giardia and Cryptosporidium is summarized here, and some important questions are raised that need to be addressed if control strategies are to be effective.

  18. Systematic Redaction for Neuroimage Data

    PubMed Central

    Matlock, Matt; Schimke, Nakeisha; Kong, Liang; Macke, Stephen; Hale, John

    2013-01-01

    In neuroscience, collaboration and data sharing are undermined by concerns over the management of protected health information (PHI) and personal identifying information (PII) in neuroimage datasets. The HIPAA Privacy Rule mandates measures for the preservation of subject privacy in neuroimaging studies. Unfortunately for the researcher, the management of information privacy is a burdensome task. Wide scale data sharing of neuroimages is challenging for three primary reasons: (i) A dearth of tools to systematically expunge PHI/PII from neuroimage data sets, (ii) a facility for tracking patient identities in redacted datasets has not been produced, and (iii) a sanitization workflow remains conspicuously absent. This article describes the XNAT Redaction Toolkit—an integrated redaction workflow which extends a popular neuroimage data management toolkit to remove PHI/PII from neuroimages. Quickshear defacing is also presented as a complementary technique for deidentifying the image data itself. Together, these tools improve subject privacy through systematic removal of PII/PHI. PMID:24179597

  19. Multiple lymphadenopathy as an initial sign of extramammary Paget disease.

    PubMed

    Hirakawa, S; Tanemura, A; Mori, H; Katayama, I; Hashimoto, K

    2011-01-01

    Extramammary Paget disease (EMPD) often develops in external genitalia. Paget cells can, however, adopt an invasive phenotype and metastasize to regional lymph nodes and beyond, leading to poor patient outcomes. Based on this clinical observation, multiple lymphadenopathy may represent an initial sign of EMPD. To address the potential significance of multiple lymph node swelling in EMPD, we report two patients with cutaneous primary EMPD who showed multiple lymphadenopathy as an initial sign during the clinical course of the disease as well as tumour metastasis. Significantly, marked lymphatic vessel growth was observed in regional lymph nodes that underwent massive tumour cell invasion. Therefore, nodal lymphangiogenesis may promote tumour cell invasion and metastasis to distant organs, including the lymph nodes, emphasizing the clinical relevance of multiple lymphadenopathy.

  20. Neuroimaging Study Designs, Computational Analyses and Data Provenance Using the LONI Pipeline

    PubMed Central

    Dinov, Ivo; Lozev, Kamen; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Pierce, Jonathan; Zamanyan, Alen; Chakrapani, Shruthi; Van Horn, John; Parker, D. Stott; Magsipoc, Rico; Leung, Kelvin; Gutman, Boris; Woods, Roger; Toga, Arthur

    2010-01-01

    Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges—management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu. PMID:20927408

  1. Preeclampsia or initial diagnosis of chronic renal disease during pregnancy.

    PubMed

    Iavazzo, C; Kalmantis, K; Bozemberg, T; Ntziora, F; Ioakeimidis, A; Paschalinopoulos, D

    2008-01-01

    An unusual case of early nephrotic syndrome without hypertension which slightly resolved after delivery is documented. Renal biopsy was performed postpartum and the diagnosis was focal and segmental glomerulosclerosis with moderate chronic renal changes. It is questioned whether the case was due to preeclampsia or was the initial diagnosis of chronic renal disease which was made during pregnancy. The role of renal biopsy in such cases is briefly discussed (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

  2. Neuroimaging of Cognition

    PubMed Central

    Dolan, R.J.

    2009-01-01

    Neuroimaging, particularly that based upon functional magnetic resonance (fMRI), has become a dominant tool in cognitive neuroscience. This review provides a personal and selective perspective on its past, present, and future. Two trends currently characterize the field that broadly reflect a pursuit of “where”- and “how”-type questions. The latter addresses basic mechanisms related to the expression of task-induced neural activity and is likely to be an increasingly important theme in the future. This trend entails an enhanced symbiosis among investigators pursuing similar questions in fields such as computational and theoretical neuroscience as well as through the detailed analysis of microcircuitry. PMID:18995825

  3. Motor initiation versus execution in normal and Parkinson's disease subjects.

    PubMed

    Montgomery, E B; Gorman, D S; Nuessen, J

    1991-09-01

    We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way.

  4. Microscopic features for initial diagnosis and disease activity evaluation in inflammatory bowel disease.

    PubMed

    Bressenot, Aude; Geboes, Karel; Vignaud, Jean-Michel; Guéant, Jean-Louis; Peyrin-Biroulet, Laurent

    2013-07-01

    Inflammatory bowel disease is characterized by 2 major entities: Crohn's disease (CD) and ulcerative colitis (UC). In clinical practice, separation of UC and CD has been based on a variety of clinical features, symptoms, endoscopic and radiological, gross and microscopic characteristics. The microscopic diagnosis of inflammatory bowel disease is based on a combination of 2 types of lesions: architectural abnormalities and inflammatory features. However, microscopic distinction between these 2 entities can be difficult and often results in an interim diagnosis of "indeterminate colitis." Recommendations are made to encourage pathologists to give an indication of the activity of the disease: in UC, biopsies are used to discriminate between quiescent disease, inactive disease, and different grades of activity; in CD, evaluation of disease activity is limited and inactivity in the biopsy may not reflect inactivity in the patient. The aim of this review was to summarize microscopic features of inflammatory bowel disease for initial diagnosis and evaluation of disease activity in both CD and UC.

  5. 4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2

    ClinicalTrials.gov

    2016-11-15

    Corticobasal Degeneration (CBD); Corticobasal Syndrome (CBS); Cortical-basal Ganglionic Degeneration (CBGD); Progressive Supranuclear Palsy (PSP); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); Oligosymptomatic/Variant Progressive Supranuclear Palsy (o/vPSP)

  6. Provenance in Neuroimaging

    PubMed Central

    MacKenzie-Graham, Allan J.; Van Horn, John D.; Woods, Roger P.; Crawford, Karen L.

    2008-01-01

    Provenance, the description of the history of a set of data, has grown more important with the proliferation of research consortia-related efforts in neuroimaging. Knowledge about the origin and history of an image is crucial for establishing data and results quality; detailed information about how it was processed, including the specific software routines and operating systems that were used, is necessary for proper interpretation, high fidelity replication and re-use. We have drafted a mechanism for describing provenance in a simple and easy to use environment, alleviating the burden of documentation from the user while still providing a rich description of an image’s provenance. This combination of ease of use and highly descriptive metadata should greatly facilitate the collection of provenance and subsequent sharing of data. PMID:18519166

  7. How the EUCERD Joint Action supported initiatives on Rare Diseases.

    PubMed

    Lynn, Stephen; Hedley, Victoria; Atalaia, Antonio; Evangelista, Teresinha; Bushby, Kate

    2017-03-01

    Joint Actions are successful initiatives from the European Commission (EC) that have helped to raise awareness and to bring significant benefit to those suffering from a rare disease (RD). In this paper, we will focus on the activities developed by the EUCERD Joint Action (EJA) and by the Orphanet Joint Action ("Orphanet Europe"). EUCERD Joint Action was co-funded by the EC and the Member States between 2012 and 2015 to help to define the activities and policies in the field of RD and foster exchange of experiences amongst Member States. This project is the continuation of previous efforts to turn RD a priority in the EC Health Programmes. "Orphanet Europe" was a Joint Action co-funded by INSERM, the French Directorate General for Health and the EC to address the need for a common portal that would gather the most update information regarding RD. This need was identified in the European Commission report "Rare Diseases: Europe's challenge" and in the Recommendation of the Council for a European RD portal. These joint actions have supported the policy development work of the European Commission, through the support of their committees for rare diseases. In this paper, the authors aim to raise awareness of the work done by the EUCERD Joint Action on behalf of the rare disease community and the policies established.

  8. Investigating motor initiation and inhibition deficits in patients with Parkinson's disease and freezing of gait using a virtual reality paradigm.

    PubMed

    Georgiades, Matthew J; Gilat, Moran; Ehgoetz Martens, Kaylena A; Walton, Courtney C; Bissett, Patrick G; Shine, James M; Lewis, Simon J G

    2016-11-19

    Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD) that is associated with deficits in motor initiation and inhibition. Understanding of underlying neurobiological mechanisms has been limited by difficulties in eliciting and objectively characterizing such gait phenomena in the clinical setting. However, recent work suggests that virtual reality (VR) techniques might offer the potential to study motor control. This study utilized a VR paradigm to explore deficits in motor initiation and stopping performance, including stop failure in PD patients with (Freezers, 31) and without (Non-Freezers, 23) FOG, and healthy age-matched Controls (15). The VR task required subjects to respond to a series of start and stop cues while navigating a corridor using ankle flexion/extension movements on foot pedals. We found that Freezers experienced slower motor output initiation and more frequent start hesitations (SHs) (initiations greater than twice a subject's usual initiation latency) compared to Non-Freezers and Controls. Freezers also showed more marked inhibitory impairments, taking significantly longer to execute motor inhibition, and experiencing an increased frequency of failed stopping in response to stop cues compared to Non-Freezers and Controls. Stopping impairments were exacerbated by stop cues requiring additional cognitive processing. These results suggest that PD patients with FOG have marked impairments in motor initiation and inhibition that are not prominent in patients without FOG, nor healthy controls. Future work combining such VR paradigms with neuroimaging techniques and intra-operative deep brain recordings may increase our understanding of these phenomena, promoting the development of novel technologies and therapeutic approaches.

  9. Neuroimaging distinction between neurological and psychiatric disorders†

    PubMed Central

    Crossley, Nicolas A.; Scott, Jessica; Ellison-Wright, Ian; Mechelli, Andrea

    2015-01-01

    Background It is unclear to what extent the traditional distinction between neurological and psychiatric disorders reflects biological differences. Aims To examine neuroimaging evidence for the distinction between neurological and psychiatric disorders. Method We performed an activation likelihood estimation meta-analysis on voxel-based morphometry studies reporting decreased grey matter in 14 neurological and 10 psychiatric disorders, and compared the regional and network-level alterations for these two classes of disease. In addition, we estimated neuroanatomical heterogeneity within and between the two classes. Results Basal ganglia, insula, sensorimotor and temporal cortex showed greater impairment in neurological disorders; whereas cingulate, medial frontal, superior frontal and occipital cortex showed greater impairment in psychiatric disorders. The two classes of disorders affected distinct functional networks. Similarity within classes was higher than between classes; furthermore, similarity within class was higher for neurological than psychiatric disorders. Conclusions From a neuroimaging perspective, neurological and psychiatric disorders represent two distinct classes of disorders. PMID:26045351

  10. Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases.

    PubMed

    Viswanathan, S; Botross, N; Rusli, B N; Riad, A

    2016-11-01

    Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients.

  11. Functional neuroimaging of extraversion-introversion.

    PubMed

    Lei, Xu; Yang, Tianliang; Wu, Taoyu

    2015-12-01

    Neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography have provided an unprecedented neurobiological perspective for research on personality traits. Evidence from task-related neuroimaging has shown that extraversion is associated with activations in regions of the anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and the amygdala. Currently, resting-state neuroimaging is being widely used in cognitive neuroscience. Initial exploration of extraversion has revealed correlations with the medial prefrontal cortex, anterior cingulate cortex, insular cortex, and the precuneus. Recent research work has indicated that the long-range temporal dependence of the resting-state spontaneous oscillation has high test-retest reliability. Moreover, the long-range temporal dependence of the resting-state networks is highly correlated with personality traits, and this can be used for the prediction of extraversion. As the long-range temporal dependence reflects real-time information updating in individuals, this method may provide a new approach to research on personality traits.

  12. Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome.

    PubMed

    Jung, Young-Chul; Chanraud, Sandra; Sullivan, Edith V

    2012-06-01

    There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke's encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff's syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.

  13. Molecular neuroimaging in degenerative dementias.

    PubMed

    Jiménez Bonilla, J F; Carril Carril, J M

    2013-01-01

    In the context of the limitations of structural imaging, brain perfusion and metabolism using SPECT and PET have provided relevant information for the study of cognitive decline. The introduction of the radiotracers for cerebral amyloid imaging has changed the diagnostic strategy regarding Alzheimer's disease, which is currently considered to be a "continuum." According to this new paradigm, the increasing amyloid load would be associated to the preclinical phase and mild cognitive impairment. It has been possible to observe "in vivo" images using 11C-PIB and PET scans. The characteristics of the 11C-PIB image include specific high brain cortical area retention in the positive cases with typical distribution pattern and no retention in the negative cases. This, in combination with 18F-FDG PET, is the basis of molecular neuroimaging as a biomarker. At present, its prognostic value is being evaluated in longitudinal studies. 11C-PIB-PET has become the reference radiotracer to evaluate the presence of cerebral amyloid. However, its availability is limited due to the need for a nearby cyclotron. Therefore, 18F labeled radiotracers are being introduced. Our experience in the last two years with 11C-PIB, first in the research phase and then as being clinically applied, has shown the utility of the technique in the clinical field, either alone or in combination with FDG. Thus, amyloid image is a useful tool for the differential diagnosis of dementia and it is a potentially useful method for early diagnosis and evaluation of future treatments.

  14. Deep Vein Thrombosis as Initial Manifestation of Whipple Disease

    PubMed Central

    Henriques, Mônica Souza de Miranda; da Paz, Alexandre Rolim; Gaertner, Ana Beatriz Person; Melo, Cibelle Ingrid Stephen; Filgueiras, Priscyanne Lins; Jerome, Rafaella Alencar

    2016-01-01

    Introduction Wipple disease (WD) is a rare chronic disease caused by the bacillus Tropheryma whipplei. Constitutive, rheumatologic, gastrointestinal, cardiac, cerebral, lymphatic, cutaneous, and ophthalmological signs are possible systemic symptoms. However, thrombotic manifestations are rarely described as “stroke-like syndrome” or arterial thrombosis. Diagnosis is based on clinical manifestations and pathological examination. Laboratory findings may include anemia, leukocytosis, and thrombocytosis. Objective We report a case of venous thrombosis as initial manifestation of WD. Case Report We describe the case of a 53-year-old male with iliofemoral vein thrombosis followed by intermittent diarrhea, loss of appetite, abdominal distension, and bloating. A mild malnutrition state with a weight loss of 13 kg, pallor (+/4 +), presence of lower-limb edema (+/4 +), and hypertympanic distended abdomen occurred. Laboratory tests on admission revealed anemia, positive inflammatory activity tests, and normal coagulation. Endoscopic examination showed villous edema with white dotted infiltrates in the second duodenal portion and intestinal lymphangiectasia in the terminal ileum. Pathological examination revealed numerous macrophages with positive periodic acid-Schiff inclusions. Venous Doppler ultrasound showed extensive deep thrombosis on the left lower limb and recanalization of the femoral vein in the right lower limb. The patient was treated with ceftriaxone and enoxaparin sodium, which led to an improvement of gastrointestinal and thrombosis symptoms. Comments Hypercoagulability, endothelial damage, vasculitis, and blood stasis are present in T. whipplei infection, which are associated with the activation of inflammatory mechanisms as well as procoagulant and thromboembolic events. WD should be part of the differential diagnosis of diseases that cause venous thrombosis of unknown origin. PMID:27920655

  15. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    PubMed

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation.

  16. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia.

    PubMed

    Dong, Y; Sun, Y-M; Liu, Z-J; Ni, W; Shi, S-S; Wu, Z-Y

    2013-04-01

    Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 ± 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes.

  17. PET neuroimaging studies of [18F]CABS13 in a double transgenic mouse model of Alzheimer’s disease and non-human primates

    PubMed Central

    Liang, Steven H.; Holland, Jason P.; Stephenson, Nickeisha A.; Kassenbrock, Alina; Rotstein, Benjamin H.; Daignault, Cory P.; Lewis, Rebecca; Collier, Lee; Hooker, Jacob M.; Vasdev, Neil

    2016-01-01

    Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([18F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the “metal hypothesis of Alzheimer’s disease”. Herein, a practical radiosynthesis of [18F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [18F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [18F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 minutes. Temporal PET neuroimaging studies were carried out in female transgenic B6C3- Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7 and 10 months of age. [18F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal non-human primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable 18F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

  18. Neuroimaging findings in primary insomnia.

    PubMed

    O'Byrne, J N; Berman Rosa, M; Gouin, J-P; Dang-Vu, T T

    2014-10-01

    State-of-the-art neuroimaging techniques have accelerated progress in the study and understanding of sleep in humans. Neuroimaging studies in primary insomnia remain relatively few, considering the important prevalence of this disorder in the general population. This review examines the contribution of functional and structural neuroimaging to our current understanding of primary insomnia. Functional studies during sleep provided support for the hyperarousal theory of insomnia. Functional neuroimaging also revealed abnormalities in cognitive and emotional processing in primary insomnia. Results from structural studies suggest neuroanatomical alterations in primary insomnia, mostly in the hippocampus, anterior cingulate cortex and orbitofrontal cortex. However, these results are not well replicated across studies. A few magnetic resonance spectroscopy studies revealed abnormalities in neurotransmitter concentrations and bioenergetics in primary insomnia. The inconsistencies among neuroimaging findings on insomnia are likely due to clinical heterogeneity, differences in imaging and overall diversity of techniques and designs employed. Larger samples, replication, as well as innovative methodologies are necessary for the progression of this perplexing, yet promising area of research.

  19. LSTGEE: longitudinal analysis of neuroimaging data

    NASA Astrophysics Data System (ADS)

    Li, Yimei; Zhu, Hongtu; Chen, Yasheng; An, Hongyu; Gilmore, John; Lin, Weili; Shen, Dinggang

    2009-02-01

    Longitudinal imaging studies are essential to understanding the neural development of neuropsychiatric disorders, substance use disorders, and normal brain. Using appropriate image processing and statistical tools to analyze the imaging, behavioral, and clinical data is critical for optimally exploring and interpreting the findings from those imaging studies. However, the existing imaging processing and statistical methods for analyzing imaging longitudinal measures are primarily developed for cross-sectional neuroimaging studies. The simple use of these cross-sectional tools to longitudinal imaging studies will significantly decrease the statistical power of longitudinal studies in detecting subtle changes of imaging measures and the causal role of time-dependent covariate in disease process. The main objective of this paper is to develop longitudinal statistics toolbox, called LSTGEE, for the analysis of neuroimaging data from longitudinal studies. We develop generalized estimating equations for jointly modeling imaging measures with behavioral and clinical variables from longitudinal studies. We develop a test procedure based on a score test statistic and a resampling method to test linear hypotheses of unknown parameters, such as associations between brain structure and function and covariates of interest, such as IQ, age, gene, diagnostic groups, and severity of disease. We demonstrate the application of our statistical methods to the detection of the changes of the fractional anisotropy across time in a longitudinal neonate study. Particularly, our results demonstrate that the use of longitudinal statistics can dramatically increase the statistical power in detecting the changes of neuroimaging measures. The proposed approach can be applied to longitudinal data with multiple outcomes and accommodate incomplete and unbalanced data, i.e., subjects with different number of measurements.

  20. Heart Rate and Initial Presentation of Cardiovascular Diseases (Caliber)

    ClinicalTrials.gov

    2013-09-17

    Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Coronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

  1. Efficient, Distributed and Interactive Neuroimaging Data Analysis Using the LONI Pipeline

    PubMed Central

    Dinov, Ivo D.; Van Horn, John D.; Lozev, Kamen M.; Magsipoc, Rico; Petrosyan, Petros; Liu, Zhizhong; MacKenzie-Graham, Allan; Eggert, Paul; Parker, Douglas S.; Toga, Arthur W.

    2009-01-01

    The LONI Pipeline is a graphical environment for construction, validation and execution of advanced neuroimaging data analysis protocols (Rex et al., 2003). It enables automated data format conversion, allows Grid utilization, facilitates data provenance, and provides a significant library of computational tools. There are two main advantages of the LONI Pipeline over other graphical analysis workflow architectures. It is built as a distributed Grid computing environment and permits efficient tool integration, protocol validation and broad resource distribution. To integrate existing data and computational tools within the LONI Pipeline environment, no modification of the resources themselves is required. The LONI Pipeline provides several types of process submissions based on the underlying server hardware infrastructure. Only workflow instructions and references to data, executable scripts and binary instructions are stored within the LONI Pipeline environment. This makes it portable, computationally efficient, distributed and independent of the individual binary processes involved in pipeline data-analysis workflows. We have expanded the LONI Pipeline (V.4.2) to include server-to-server (peer-to-peer) communication and a 3-tier failover infrastructure (Grid hardware, Sun Grid Engine/Distributed Resource Management Application API middleware, and the Pipeline server). Additionally, the LONI Pipeline provides three layers of background-server executions for all users/sites/systems. These new LONI Pipeline features facilitate resource-interoperability, decentralized computing, construction and validation of efficient and robust neuroimaging data-analysis workflows. Using brain imaging data from the Alzheimer's Disease Neuroimaging Initiative (Mueller et al., 2005), we demonstrate integration of disparate resources, graphical construction of complex neuroimaging analysis protocols and distributed parallel computing. The LONI Pipeline, its features, specifications

  2. Disease progression in non-erosive reflux disease (NERD): impact of initial esophageal acid exposure.

    PubMed

    Chen, C L; Liu, T T; Yi, C H

    2010-11-01

    We investigated the 5-year clinical course in a cohort of patients with typical reflux symptoms and negative endoscopy. Prospective follow-up was conducted in patients with non-erosive reflux disease (NERD) for at least 5 years after initial evaluation with esophageal pH monitoring and upper gastrointestinal endoscopy. Within the last year of follow-up, reflux symptoms occurred in 27 of the 30 patients (90%). Twenty-five of twenty-seven symptomatic patients (93%) were on acid suppression therapy. The majority of our patients (70%) remained unchanged regarding their endoscopic status over 5 years. Progression to erosive esophagitis occurred in four patients with Los Angeles (LA) A (13%), three patients with LA B (10%), and two patients with LA C (7%). The presence of pathological acid exposure did not alter the presence of reflux symptoms over 5 years. Disease progression to erosive esophagitis occurred more frequently in patients with pathological acid exposure than those without pathological acid exposure (P= 0.025). Most NERD patients have symptoms and require acid suppression therapy 5 years after their initial diagnosis. Initial pathological acid exposure does not influence the use of acid suppression; however, it does influence the progression of NERD within 5 years of follow-up.

  3. Neuroimaging evaluation in refractory epilepsy

    PubMed Central

    Granados, Ana M; Orejuela, Juan F

    2015-01-01

    Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

  4. Building better biomarkers: brain models in translational neuroimaging.

    PubMed

    Woo, Choong-Wan; Chang, Luke J; Lindquist, Martin A; Wager, Tor D

    2017-02-23

    Despite its great promise, neuroimaging has yet to substantially impact clinical practice and public health. However, a developing synergy between emerging analysis techniques and data-sharing initiatives has the potential to transform the role of neuroimaging in clinical applications. We review the state of translational neuroimaging and outline an approach to developing brain signatures that can be shared, tested in multiple contexts and applied in clinical settings. The approach rests on three pillars: (i) the use of multivariate pattern-recognition techniques to develop brain signatures for clinical outcomes and relevant mental processes; (ii) assessment and optimization of their diagnostic value; and (iii) a program of broad exploration followed by increasingly rigorous assessment of generalizability across samples, research contexts and populations. Increasingly sophisticated models based on these principles will help to overcome some of the obstacles on the road from basic neuroscience to better health and will ultimately serve both basic and applied goals.

  5. Disease management. A global cost-containing initiative?

    PubMed

    Bloor, K; Maynard, A

    2000-06-01

    Disease management has been marketed by healthcare industry providers as a way of improving resource allocation in healthcare and containing costs. However, to achieve improved efficiency in healthcare requires the guidelines and protocols in the disease management process to be based on sound evidence of effectiveness and cost effectiveness. This has not always been the case. The approach itself has an inadequate evidence base in terms of randomised controlled trials, other rigorous methods of evaluation and the results of economic evaluation. Disease management can be viewed as an attempt by pharmaceutical companies to undertake forward vertical integration into other parts of the healthcare process. This could reduce uncertainty for purchasers and reduce transaction costs, thereby potentially facilitating both healthcare expenditure control and efficiency. However, such cost savings may be outweighed by a concentration of power in disease management (pharmaceutical) companies, and the exploitation of such power to inflate expenditure and misallocate resources. Disease management must be appraised with care.

  6. 78 FR 17412 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... Diseases in Africa, FOA GH13-002, initial review. In accordance with Section 10(a)(2) of the Federal... and Evaluation of Programs for the Elimination and Control of Neglected Tropical Diseases in...

  7. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... and Disease Prevention Research Centers, Funding Opportunity Announcement (FOA) DP14-001, initial... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times And Dates 8...

  8. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... and Disease Prevention Research Centers, Funding Opportunity Announcement (FOA) DP14-001, initial... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times and Dates 8...

  9. Advanced Neuroimaging of Tinnitus.

    PubMed

    Raghavan, Prashant; Steven, Andrew; Rath, Tanya; Gandhi, Dheeraj

    2016-05-01

    Although tinnitus may originate in damage to the peripheral auditory apparatus, its perception and distressing symptomatology are consequences of alterations to auditory, sensory, and limbic neural networks. This has been described in several studies, some using advanced structural MR imaging techniques such as diffusion tensor imaging. An understanding of these complex changes could enable development of targeted treatment. New MR imaging techniques enabling detailed depiction of the labyrinth may be useful when diagnosis of Meniere disease is equivocal. Advances in computed tomography and MR imaging have enabled noninvasive diagnosis of dural arteriovenous fistulae.

  10. Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative

    PubMed Central

    Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

    2002-01-01

    Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined. PMID:11932231

  11. Dracunculiasis (Guinea worm disease) and the eradication initiative.

    PubMed

    Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

    2002-04-01

    Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined.

  12. [Correlation between EEG and neuroimaging].

    PubMed

    Tobimatsu, Shozo

    2012-01-01

    The present state of knowledge of physiological mechanisms underlying nonepileptiform EEG abnormalities is reviewed to clarify the correlation between EEG and neuroimaging. Focal and widespread slow waves, background abnormalities, and bursts of rhythmic slow activity are discussed. EEG phenomena were correlated with lesion size, location, type (white matter vs. gray matter, high density vs. low density), and mass effect. Clinical and experimental accumulated over the past five decades suggest that polymorphic slow activity is generated in cerebral cortex by layers of pyramidal cells and is probably due to partial deafferentation from subcortical areas. Unilateral background activity changes are probably thalamic dysfunction, and bilateral paroxysmal slow activity is due to abnormal thalamocortical circuits combined with cortical pathology. Paroxysmal discharges indicate the presence of epilepsy with possible brain lesion(s). The EEG is a functional test and provides us complementary information to neuroimaging studies.

  13. Initial studies on "six months disease" in sheep.

    PubMed

    Pyakural, S; Singh, N B

    1976-01-17

    Enterotoxaemia in sheep due to Clostridium welchii type D was indicated by field and laboratory investigations in Nepal. Morphological, cultural, biochemical, biological and toxin-producing characteristics observed were used to type the isolates. In anaerobic meat medium, all isolates produced pinkish discoloration of meat. All the strains fermented lactose, maltose, dextrose and sucrose whereas, salicine was fermented only by 17 strains. All but five strains were MR negative. Out of 200 isolated, 166 produced both alpha and epsilon toxins and the remaining 34 non-toxogenic strains are likely to be variants which have lost their toxogenicity. Epidemiologically the local name "Six months disease" and enterotoxaemia are considered to be identical diseases.

  14. [Obstructive uropathy as initial manifestation of Crohn disease].

    PubMed

    Hernández Jaras, J; García-Samaniego Rey, J; Paraiso Cuevas, V; Castaños-Mollor Penalva, R; Pajares García, J M; Traver Aguilar, J A

    1990-10-01

    A patient with renal colicky pain caused by urinary tract obstruction, as a result of psoas abscess, is presented. It was the first manifestation of Crohn's disease. A Gram negative bacteria was isolated from the abscess. The CT images performed to evaluate the abscess suggested this etiology, even though there were no previous symptoms.

  15. 78 FR 66938 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: This notice concerns.... Department of Health and Human Services, Centers for Disease Control and Prevention, from October 1-16,...

  16. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned SEP: Times and...

  17. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Occupational... 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control...

  18. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: This notice concerns.... Department of Health and Human Services, Centers for Disease Control and Prevention, from October 1-16,...

  19. The Human Connectome Project's neuroimaging approach.

    PubMed

    Glasser, Matthew F; Smith, Stephen M; Marcus, Daniel S; Andersson, Jesper L R; Auerbach, Edward J; Behrens, Timothy E J; Coalson, Timothy S; Harms, Michael P; Jenkinson, Mark; Moeller, Steen; Robinson, Emma C; Sotiropoulos, Stamatios N; Xu, Junqian; Yacoub, Essa; Ugurbil, Kamil; Van Essen, David C

    2016-08-26

    Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease.

  20. A review of neuroimaging findings in repetitive brain trauma.

    PubMed

    Koerte, Inga K; Lin, Alexander P; Willems, Anna; Muehlmann, Marc; Hufschmidt, Jakob; Coleman, Michael J; Green, Isobel; Liao, Huijun; Tate, David F; Wilde, Elisabeth A; Pasternak, Ofer; Bouix, Sylvain; Rathi, Yogesh; Bigler, Erin D; Stern, Robert A; Shenton, Martha E

    2015-05-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE.

  1. Neuroimaging Endophenotypes in Autism Spectrum Disorder

    PubMed Central

    Mahajan, Rajneesh; Mostofsky, Stewart H.

    2015-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response and lead to the development of new therapies. PMID:26234701

  2. Tinnitus: perspectives from human neuroimaging.

    PubMed

    Elgoyhen, Ana Belén; Langguth, Berthold; De Ridder, Dirk; Vanneste, Sven

    2015-10-01

    Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients.

  3. Neuroimaging findings in late-onset schizophrenia and bipolar disorder.

    PubMed

    Hahn, Changtae; Lim, Hyun Kook; Lee, Chang Uk

    2014-03-01

    In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimaging studies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were "(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset." Articles that were published in English before October 2013 were included. There were a few neuroimaging studies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimaging studies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB.

  4. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    PubMed

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S; Toledo, Jon B; Weintraub, Daniel; Galasko, Douglas R; Irwin, David J; Van Deerlin, Vivianna; Chen-Plotkin, Alice S; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W; Chowdhury, Sohini; Trojanowski, John Q; Shaw, Leslie M

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

  5. Neuroimaging Week: A Novel, Engaging, and Effective Curriculum for Teaching Neuroimaging to Junior Psychiatric Residents

    ERIC Educational Resources Information Center

    Downar, Jonathan; Krizova, Adriana; Ghaffar, Omar; Zaretsky, Ari

    2010-01-01

    Objective: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice.…

  6. A simple tool for neuroimaging data sharing

    PubMed Central

    Haselgrove, Christian; Poline, Jean-Baptiste; Kennedy, David N.

    2014-01-01

    Data sharing is becoming increasingly common, but despite encouragement and facilitation by funding agencies, journals, and some research efforts, most neuroimaging data acquired today is still not shared due to political, financial, social, and technical barriers to sharing data that remain. In particular, technical solutions are few for researchers that are not a part of larger efforts with dedicated sharing infrastructures, and social barriers such as the time commitment required to share can keep data from becoming publicly available. We present a system for sharing neuroimaging data, designed to be simple to use and to provide benefit to the data provider. The system consists of a server at the International Neuroinformatics Coordinating Facility (INCF) and user tools for uploading data to the server. The primary design principle for the user tools is ease of use: the user identifies a directory containing Digital Imaging and Communications in Medicine (DICOM) data, provides their INCF Portal authentication, and provides identifiers for the subject and imaging session. The user tool anonymizes the data and sends it to the server. The server then runs quality control routines on the data, and the data and the quality control reports are made public. The user retains control of the data and may change the sharing policy as they need. The result is that in a few minutes of the user’s time, DICOM data can be anonymized and made publicly available, and an initial quality control assessment can be performed on the data. The system is currently functional, and user tools and access to the public image database are available at http://xnat.incf.org/. PMID:24904398

  7. Neuroimaging of Freezing of Gait

    PubMed Central

    Fasano, Alfonso; Herman, Talia; Tessitore, Alessandro; Strafella, Antonio P.; Bohnen, Nicolaas I.

    2015-01-01

    Abstract Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the “executive-attention” network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping. In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon. PMID:25757831

  8. What's new in neuroimaging methods?

    PubMed Central

    Bandettini, Peter A.

    2009-01-01

    The rapid advancement of neuroimaging methodology and availability has transformed neuroscience research. The answers to many questions that we ask about how the brain is organized depend on the quality of data that we are able to obtain about the locations, dynamics, fluctuations, magnitudes, and types of brain activity and structural changes. In this review, an attempt is made to take a snapshot of the cutting edge of a small component of the very rapidly evolving field of neuroimaging. For each area covered, a brief context is provided along with a summary of a few of the current developments and issues. Then, several outstanding papers, published in the past year or so, are described, providing an example of the directions in which each area is progressing. The areas covered include functional MRI (fMRI), voxel based morphometry (VBM), diffusion tensor imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG), optical imaging, and positron emission tomography (PET). More detail is included on fMRI, as subsections include: functional MRI interpretation, new functional MRI contrasts, MRI technology, MRI paradigms and processing, and endogenous oscillations in functional MRI. PMID:19338512

  9. Neuroimaging in repetitive brain trauma

    PubMed Central

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. PMID:25031630

  10. Neuroimaging in repetitive brain trauma.

    PubMed

    Ng, Thomas Sc; Lin, Alexander P; Koerte, Inga K; Pasternak, Ofer; Liao, Huijun; Merugumala, Sai; Bouix, Sylvain; Shenton, Martha E

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.

  11. Finger movement improves ankle control for gait initiation in patients with Parkinson's disease.

    PubMed

    Hiraoka, K; Kamata, N; Iwata, A; Minamida, F; Abe, K

    2008-01-01

    The purpose of this study was to investigate the effect of finger movement on ankle control for gait initiation in patients with Parkinson's disease (PD patients). The subjects were 13 PD patients and 6 age-matched healthy adults. The subjects moved fingers before or after gait initiation, or initiated gait without finger movement. Ankle joint movement in the stance leg was recorded to estimate the duration of ankle dorsiflexion (DIF duration), which reflects the degree of disturbance in ankle control for gait initiation in PD patients. In the PD patients with prolonged D/F duration, finger movement that preceded gait initiation shortened the D/F duration, but in the PD patients without prolonged D/F duration and in healthy subjects, the effect was not found. Accordingly, finger movement that precedes gait initiation improves ankle control for gait initiation in PD patients who suffer disturbance in ankle control for gait initiation.

  12. Effects of cognitive task on gait initiation in Parkinson disease: evidence of motor prioritization?

    PubMed

    Nocera, Joe R; Roemmich, Ryan; Elrod, Jonathan; Altmann, Lori J P; Hass, Chris J

    2013-01-01

    While much is known about the effects of dual tasking on cyclical and continuous motor performance (e.g., locomotion), there is a paucity of information on the effect of dual tasking on the initiation of movement. Therefore, the purpose of this study was to investigate the effect of a concurrent cognitive task on gait initiation in three groups: patients with Parkinson disease, healthy older adults, and healthy young adults. We examined the anticipatory postural adjustment displacements and velocities during single-task gait initiation as well as two dual-task conditions: (1) 0-back + gait initiation and (2) 2-back + gait initiation. The Parkinson disease group exhibited less anticipatory postural adjustment displacement and velocity than their aged-matched healthy peers and young adults during the single- and dual-task gait initiation settings (p < 0.05). Of interest was the finding of no additional effect on anticipatory postural adjustment displacement or velocity of gait initiation during the dual-task conditions in any group, including the Parkinson disease group. More traditionally studied gait/balance dual-task paradigms have demonstrated both motor and cognitive decline. Therefore, our results may suggest a prioritization of more "intentional" movement task (e.g., gait initiation) while dual tasking in Parkinson disease.

  13. Intergenerational Neuroimaging of Human Brain Circuitry.

    PubMed

    Ho, Tiffany C; Sanders, Stephan J; Gotlib, Ian H; Hoeft, Fumiko

    2016-10-01

    Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed light on the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here we highlight recent intergenerational neuroimaging studies and provide recommendations for future work.

  14. Neuroimaging of Cognitive Load in Instructional Multimedia

    ERIC Educational Resources Information Center

    Whelan, Robert R.

    2007-01-01

    This paper reviews research literature on cognitive load measurement in learning and neuroimaging, and describes a mapping between the main elements of cognitive load theory and findings in functional neuroanatomy. It is argued that these findings may lead to the improved measurement of cognitive load using neuroimaging. The paper describes how…

  15. Neuroimaging and Research into Second Language Acquisition

    ERIC Educational Resources Information Center

    Sabourin, Laura

    2009-01-01

    Neuroimaging techniques are becoming not only more and more sophisticated but are also coming to be increasingly accessible to researchers. One thing that one should take note of is the potential of neuroimaging research within second language acquisition (SLA) to contribute to issues pertaining to the plasticity of the adult brain and to general…

  16. Commentary: Applications of functional neuroimaging to civil litigation of mild traumatic brain injury.

    PubMed

    Granacher, Robert P

    2008-01-01

    The current definition of mild traumatic brain injury (MTBI) is in flux. Presently, there are at least three working definitions of this disorder in the United States, with no clear consensus. Functional neuroimaging, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), initially showed promise in their ability to improve the diagnostic credibility of MTBI. Over the past decade, that promise has not been fulfilled and there is a paucity of quality studies or standards for the application of functional neuroimaging to traumatic brain injury, particularly in litigation. The legal profession is ahead of the science in this matter. The emergence of neurolaw is driving a growing use of functional neuroimaging, as a sole imaging modality, used by lawyers in an attempt to prove MTBI at trial. The medical literature on functional neuroimaging and its applications to MTBI is weak scientifically, sparse in quality publications, lacking in well-designed controlled studies, and currently does not meet the complete standards of Daubert v. Merrell Dow Pharmaceuticals, Inc., for introduction of scientific evidence at trial. At the present time, there is a clear lack of clinical correlation between functional neuroimaging of MTBI and behavioral, neuropsychological, or structural neuroimaging deficits. The use of SPECT or PET, without concurrent clinical correlation with structural neuroimaging (CT or MRI), is not recommended to be offered as evidence of MTBI in litigation.

  17. 77 FR 31358 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial Review The meeting announced below concerns Research...

  18. 78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity Building Assistance for High Impact...

  19. Vitamin D deficiency and the lung: disease initiator or disease modifier?

    PubMed

    Foong, Rachel E; Zosky, Graeme R

    2013-07-26

    Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing. This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms? In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease.

  20. The role of neuroimaging in the diagnosis of headache disorders

    PubMed Central

    Obermann, Mark

    2013-01-01

    Headache is a common clinical feature in patients in the emergency room and in general neurology clinics. For physicians not experienced in headache disorders it might be difficult sometimes to decide in which patients neuroimaging is necessary to diagnose an underlying brain pathology and in which patients cerebral imaging is unnecessary. Most patients presenting to the primary-care physician with a nonacute headache and no further neurological signs or symptoms will not be suffering from an underlying serious condition. This review focuses on the main primary headache diseases, including migraine, tension-type headache and cluster headache, as well as frequent secondary headache entities with common clinical presentation and appropriate diagnostic and therapeutic algorithms to help guide the decision on the utilization of neuroimaging in the diagnostic workup. PMID:24228072

  1. Burning Tongue as Initial Presentation of Celiac Disease in an Elderly Woman: A Case Report.

    PubMed

    Sherman, Andrea; Zamulko, Alla

    2016-06-01

    There are few reports in the literature where celiac disease presents with tongue manifestations, although atypical presentations of celiac disease are not uncommon. This case report highlights an atypical presentation of celiac disease in an elderly female. Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Complete symptom improvement was noted by 10 weeks into the initiation of a gluten free diet. Celiac disease can present at any age and should be considered as a differential in findings of malabsorption and gastrointestinal symptoms.

  2. Workflow-based approaches to neuroimaging analysis.

    PubMed

    Fissell, Kate

    2007-01-01

    Analysis of functional and structural magnetic resonance imaging (MRI) brain images requires a complex sequence of data processing steps to proceed from raw image data to the final statistical tests. Neuroimaging researchers have begun to apply workflow-based computing techniques to automate data analysis tasks. This chapter discusses eight major components of workflow management systems (WFMSs): the workflow description language, editor, task modules, data access, verification, client, engine, and provenance, and their implementation in the Fiswidgets neuroimaging workflow system. Neuroinformatics challenges involved in applying workflow techniques in the domain of neuroimaging are discussed.

  3. The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome

    PubMed Central

    Rafii, Michael S.; Wishnek, Hannah; Brewer, James B.; Donohue, Michael C.; Ness, Seth; Mobley, William C.; Aisen, Paul S.; Rissman, Robert A.

    2015-01-01

    To gain further knowledge on the preclinical phase of Alzheimer’s disease (AD), we sought to characterize cognitive performance, neuroimaging and plasma-based AD biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30–60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid positron emission tomography (PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and retinal amyloid imaging. In addition, plasma beta-amyloid (Aβ) species were measured and Apolipoprotein E (ApoE) genotyping was performed. Results from our multimodal analysis suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971. PMID:26441570

  4. Molecular Neuroimaging in Posttraumatic Stress Disorder

    PubMed Central

    Im, Jooyeon Jamie; Namgung, Eun; Choi, Yejee; Kim, Jung Yoon; Rhie, Sandy Jeong

    2016-01-01

    Over the past decade, an increasing number of neuroimaging studies have provided insight into the neurobiological mechanisms of posttraumatic stress disorder (PSTD). In particular, molecular neuroimaging techniques have been employed in examining metabolic and neurochemical processes in PTSD. This article reviews molecular neuroimaging studies in PTSD and focuses on findings using three imaging modalities including positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS). Although there were some inconsistences in the findings, patients with PTSD showed altered cerebral metabolism and perfusion, receptor bindings, and metabolite profiles in the limbic regions, medial prefrontal cortex, and temporal cortex. Studies that have investigated brain correlates of treatment response are also reviewed. Lastly, the limitations of the molecular neuroimaging studies and potential future research directions are discussed. PMID:28035179

  5. Developments in functional neuroimaging techniques

    SciTech Connect

    Aine, C.J.

    1995-03-01

    A recent review of neuroimaging techniques indicates that new developments have primarily occurred in the area of data acquisition hardware/software technology. For example, new pulse sequences on standard clinical imagers and high-powered, rapidly oscillating magnetic field gradients used in echo planar imaging (EPI) have advanced MRI into the functional imaging arena. Significant developments in tomograph design have also been achieved for monitoring the distribution of positron-emitting radioactive tracers in the body (PET). Detector sizes, which pose a limit on spatial resolution, have become smaller (e.g., 3--5 mm wide) and a new emphasis on volumetric imaging has emerged which affords greater sensitivity for determining locations of positron annihilations and permits smaller doses to be utilized. Electromagnetic techniques have also witnessed growth in the ability to acquire data from the whole head simultaneously. EEG techniques have increased their electrode coverage (e.g., 128 channels rather than 16 or 32) and new whole-head systems are now in use for MEG. But the real challenge now is in the design and implementation of more sophisticated analyses to effectively handle the tremendous amount of physiological/anatomical data that can be acquired. Furthermore, such analyses will be necessary for integrating data across techniques in order to provide a truly comprehensive understanding of the functional organization of the human brain.

  6. Functional near-infrared neuroimaging.

    PubMed

    Izzetoglu, Kurtulus; Bunce, Scott; Izzetoglu, Meltem; Onaral, Banu; Pourrezaei, Kambiz

    2004-01-01

    Functional near-infrared (fNIR) spectroscopy is a wearable neuroimaging device that enables the continuous, non-invasive, and portable monitoring of changes in blood oxygen and blood volume related to human brain function. Over the last three years, studies in the laboratory and under field conditions have established the positive correlation between a participant's performance and oxygenation responses as a function of task load. Our findings indicate that fNIR can effectively monitor attention and working memory in real-life situations. These experimental outcomes compare favorably with functional magnetic resonance imaging (fMRI) studies, and in particular, with the blood oxygenation level dependent (BOLD) signal. The capacity to monitor brain hemodynamics with a wearable device holds promise for the use of fNIR in the creation of a symbiotic relationship between the user and his/her everyday environment. Moreover, under operational conditions, the fNIR system is amenable to integration with other established physiological and neurobehavioral measures, including EEG, eye tracking, pupil reflex, heart rate variability, respiration and electrodermal activity.

  7. Neonatal Neuroimaging Findings in Inborn Errors of Metabolism

    PubMed Central

    Poretti, Andrea; Blaser, Susan I.; Lequin, Maarten H.; Fatemi, Ali; Meoded, Avner; Northington, Frances J.; Boltshauser, Eugen; Huisman, Thierry A.G.M.

    2014-01-01

    Individually, metabolic disorders are rare, but overall they account for a significant number of neonatal disorders affecting the central nervous system. The neonatal clinical manifestations of inborn errors of metabolism (IEMs) are characterized by nonspecific systemic symptoms that may mimic more common acute neonatal disorders like sepsis, severe heart insufficiency, or neonatal hypoxic-ischemic encephalopathy. Certain IEMs presenting in the neonatal period may also be complicated by sepsis and cardiomyopathy. Early diagnosis is mandatory to prevent death and permanent long-term neurological impairments. Although neuroimaging findings are rarely specific, they play a key role in suggesting the correct diagnosis, limiting the differential diagnosis, and may consequently allow early initiation of targeted metabolic and genetic laboratory investigations and treatment. Neuroimaging may be especially helpful to distinguish metabolic disorders from other more common causes of neonatal encephalopathy, as a newborn may present with an IEM prior to the availability of the newborn screening results. It is therefore important that neonatologists, pediatric neurologists, and pediatric neuroradiologists are familiar with the neuroimaging findings of metabolic disorders presenting in the neonatal time period. PMID:22566357

  8. Neuroimaging characteristics of dementia with Lewy bodies.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2014-01-01

    This review summarises the findings and applications from neuroimaging studies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our

  9. Visual systems for interactive exploration and mining of large-scale neuroimaging data archives.

    PubMed

    Bowman, Ian; Joshi, Shantanu H; Van Horn, John D

    2012-01-01

    While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimaging studies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining.

  10. Visual Systems for Interactive Exploration and Mining of Large-Scale Neuroimaging Data Archives

    PubMed Central

    Bowman, Ian; Joshi, Shantanu H.; Van Horn, John D.

    2012-01-01

    While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimaging studies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining. PMID:22536181

  11. Neuroimaging essentials in essential tremor: A systematic review

    PubMed Central

    Sharifi, Sarvi; Nederveen, Aart J.; Booij, Jan; van Rootselaar, Anne-Fleur

    2014-01-01

    Background Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. Methods We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, MRI, VBM, DWI, fMRI, PET and SPECT, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. Results A total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Discussion and conclusion Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily

  12. Yield of Emergent Neuroimaging in Children with New-Onset Seizure and Status Epilepticus

    PubMed Central

    Lyons, Todd W.; Johnson, Kara B.; Michelson, Kenneth A.; Nigrovic, Lise E.; Loddenkemper, Tobias; Prabhu, Sanjay P.; Kimia MD, Amir A.

    2017-01-01

    PURPOSE To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. METHOD We performed a cross-sectional study of children seen at a single ED between 1995–2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 minutes or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. RESULTS We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29–43%) children with 15 (8.5%, 95% confidence interval 5.2–14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. CONCLUSION A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. PMID:26773658

  13. Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

  14. 76 FR 33305 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ..., initial review.'' Contact Person for More Information: J. Felix Rogers, Ph.D., M.P.H., Scientific Review...: Time and Date: 8 a.m.--5 p.m., July 11, 2011 (Closed). Place: Intercontinental Hotel Buckhead, 3315... for Disease Control and Prevention. BILLING CODE 4163-18-P...

  15. 77 FR 5257 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... Indonesia, FOA CK12-002, initial review.'' Contact Person for More Information: Greg Anderson, M.P.H., M.S... Date: 1 p.m.-5 p.m., March 26, 2012 (Closed). Place: Teleconference. Status: The meeting will be closed... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  16. 78 FR 17411 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ...-005, initial review.'' Contact Person for More Information: Hylan D. Shoob, Ph.D., M.S.P.H... and Prevention (CDC) announces the aforementioned meeting: Time and Date: 11:00 a.m.-3:00 p.m., May 21... Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  17. Source counting in MEG neuroimaging

    NASA Astrophysics Data System (ADS)

    Lei, Tianhu; Dell, John; Magee, Ralphy; Roberts, Timothy P. L.

    2009-02-01

    Magnetoencephalography (MEG) is a multi-channel, functional imaging technique. It measures the magnetic field produced by the primary electric currents inside the brain via a sensor array composed of a large number of superconducting quantum interference devices. The measurements are then used to estimate the locations, strengths, and orientations of these electric currents. This magnetic source imaging technique encompasses a great variety of signal processing and modeling techniques which include Inverse problem, MUltiple SIgnal Classification (MUSIC), Beamforming (BF), and Independent Component Analysis (ICA) method. A key problem with Inverse problem, MUSIC and ICA methods is that the number of sources must be detected a priori. Although BF method scans the source space on a point-to-point basis, the selection of peaks as sources, however, is finally made by subjective thresholding. In practice expert data analysts often select results based on physiological plausibility. This paper presents an eigenstructure approach for the source number detection in MEG neuroimaging. By sorting eigenvalues of the estimated covariance matrix of the acquired MEG data, the measured data space is partitioned into the signal and noise subspaces. The partition is implemented by utilizing information theoretic criteria. The order of the signal subspace gives an estimate of the number of sources. The approach does not refer to any model or hypothesis, hence, is an entirely data-led operation. It possesses clear physical interpretation and efficient computation procedure. The theoretical derivation of this method and the results obtained by using the real MEG data are included to demonstrates their agreement and the promise of the proposed approach.

  18. Analysis of residual disease following preoperative radiotherapy versus initial surgery in endometrial carcinoma

    SciTech Connect

    Chung, C.K.; Stryker, J.A.; Nahhas, W.A.; Cunningham, D.E.; Mortel, R.

    1982-02-01

    A clinicopathologic study of residual disease following pre-operative radiotherapy (RT) in 67 patients and initial surgery in 40 patients with early invasive endometrial carcinoma is presented. In 10%, extrauterine spread was found at operation. In 10% of patients, the histologic type, and in 19% the grade of tumor, differed between the curettage and hysterectomy specimens. Pre-op RT altered the depth of myometrial invasion and frequency of vascular invasion, but there was no evidence that irradiation itself affected the histologic type or grade of tumor. The patients with residual tumor after pre-op RT had significantly more cancer-related deaths than those without residual disease. The high risk factors were deep myometrial invasion and residual disease outside the uterus. Vascular invasion did not affect the prognosis in this series. The importance of surgical-pathologic staging by initial surgery is discussed.

  19. Gene Interactions and Structural Brain Change in Early-Onset Alzheimer's Disease Subjects Using the Pipeline Environment

    PubMed Central

    Dinov, Ivo D.; Zamanyan, Alen; Shi, Ran; Genco, Alex; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

    2015-01-01

    Objective This article investigates subjects aged 55 to 65 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to broaden our understanding of early-onset (EO) cognitive impairment using neuroimaging and genetics biomarkers. Methods Nine of the subjects had EO-AD (Alzheimer's disease) and 27 had EO-MCI (mild cognitive impairment). The 15 most important neuroimaging markers were extracted with the Global Shape Analysis (GSA) Pipeline workflow. The 20 most significant single nucleotide polymorphisms (SNPs) were chosen and were associated with specific neuroimaging biomarkers. Results We identified associations between the neuroimaging phenotypes and genotypes for a total of 36 subjects. Our results for all the subjects taken together showed the most significant associations between rs7718456 and L_hippocampus (volume), and between rs7718456 and R_hippocampus (volume). For the 27 MCI subjects, we found the most significant associations between rs6446443 and R_superior_frontal_gyrus (volume), and between rs17029131 and L_Precuneus (volume). For the nine AD subjects, we found the most significant associations between rs16964473 and L_rectus gyrus (surface area), and between rs12972537 and L_rectus_gyrus (surface area). Conclusion We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 36 EO subjects in terms of neuroimaging genetics. However, larger sample sizes are needed to ensure that the effects will be detectable for a reasonable false-positive error rate using the GSA and Plink Pipeline workflows. PMID:25670955

  20. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    PubMed Central

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  1. Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

    PubMed

    Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

    2017-04-01

    Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P < 0.001) with the age of healthy subjects, while this defined trend was disrupted by disease. Microbiota-for-age Z-scores (MAZ, here defined as immaturity) were relative stable among healthy shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators.

  2. Tobacco-related disease burden and preventive initiatives in China. Global health and the chronic diseases: perspective, policy and practice.

    PubMed

    Niu, Bolin

    2011-06-01

    The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year.

  3. Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity

    PubMed Central

    Hegde, Ganapati V.; de la Cruz, Cecile; Eastham-Anderson, Jeffrey; Zheng, Yanyan; Sweet-Cordero, E. Alejandro; Jackson, Erica L.

    2012-01-01

    Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell’s ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell’s ability to drive disease recurrence. PMID:23115623

  4. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    PubMed

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  5. Multimodal neuroimaging computing: the workflows, methods, and platforms.

    PubMed

    Liu, Sidong; Cai, Weidong; Liu, Siqi; Zhang, Fan; Fulham, Michael; Feng, Dagan; Pujol, Sonia; Kikinis, Ron

    The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms.

  6. Multimodal neuroimaging computing: the workflows, methods, and platforms.

    PubMed

    Liu, Sidong; Cai, Weidong; Liu, Siqi; Zhang, Fan; Fulham, Michael; Feng, Dagan; Pujol, Sonia; Kikinis, Ron

    2015-09-01

    The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms.

  7. Neuroimaging Coordination Dynamics in the Sport Sciences

    PubMed Central

    Jantzen, Kelly J.; Oullier, Olivier; Kelso, J.A. Scott

    2008-01-01

    Key methodological issues for designing, analyzing, and interpreting neuroimaging experiments are presented from the perspective of the framework of Coordination Dynamics. To this end, a brief overview of Coordination Dynamics is introduced, including the main concepts of control parameters and collective variables, theoretical modeling, novel experimental paradigms, and cardinal empirical findings. Basic conceptual and methodological issues for the design and implementation of coordination experiments in the context of neuroimaging are discussed. The paper concludes with a presentation of neuroimaging findings central to understanding the neural basis of coordination and addresses their relevance for the sport sciences. The latter include but are not restricted to learning and practice-related issues, the role of mental imagery, and the recovery of function following brain injury. PMID:18602998

  8. Molecular neuroimaging of emotional decision-making.

    PubMed

    Takahashi, Hidehiko

    2013-04-01

    With the dissemination of non-invasive human neuroimaging techniques such as fMRI and the advancement of cognitive science, neuroimaging studies focusing on emotions and social cognition have become established. Along with this advancement, behavioral economics taking emotional and social factors into account for economic decisions has been merged with neuroscientific studies, and this interdisciplinary approach is called neuroeconomics. Past neuroeconomics studies have demonstrated that subcortical emotion-related brain structures play an important role in "irrational" decision-making. The research field that investigates the role of central neurotransmitters in this process is worthy of further development. Here, we provide an overview of recent molecular neuroimaging studies to further the understanding of the neurochemical basis of "irrational" or emotional decision-making and the future direction, including clinical implications, of the field.

  9. Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin.

    PubMed

    Youn, Youngmin; Kim, Jisoo; Hong, Young Mi; Sohn, Sejung

    2016-04-01

    Forty-three patients with Kawasaki disease who were resistant to initial intravenous immunoglobulin (IVIG) were randomized to receive either a second dose of IVIG (n = 32) or an infliximab (n = 11). With IVIG retreatment 21 patients (65.6%) responded, and with infliximab 10 patients (90.9%) responded. The infliximab group had shorter duration of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar.

  10. [Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use].

    PubMed

    Arbizu, J; Luquin, M R; Abella, J; de la Fuente-Fernández, R; Fernandez-Torrón, R; García-Solís, D; Garrastachu, P; Jiménez-Hoyuela, J M; Llaneza, M; Lomeña, F; Lorenzo-Bosquet, C; Martí, M J; Martinez-Castrillo, J C; Mir, P; Mitjavila, M; Ruiz-Martínez, J; Vela, L

    2014-01-01

    Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression.

  11. Proliferation-Independent Initiation of Biliary Cysts in Polycystic Liver Diseases.

    PubMed

    Beaudry, Jean-Bernard; Cordi, Sabine; Demarez, Céline; Lepreux, Sébastien; Pierreux, Christophe E; Lemaigre, Frédéric P

    2015-01-01

    Biliary cysts in adult patients affected by polycystic liver disease are lined by cholangiocytes that proliferate, suggesting that initiation of cyst formation depends on proliferation. Here, we challenge this view by analyzing cyst-lining cell proliferation and differentiation in Cpk mouse embryos and in livers from human fetuses affected by Autosomal Recessive Polycystic Kidney Disease (ARPKD), at early stages of cyst formation. Proliferation of fetal cholangiocyte precursors, measured by immunostaining in human and mouse livers, was low and did not differ between normal and ARPKD or Cpk livers, excluding excessive proliferation as an initiating cause of liver cysts. Instead, our analyses provide evidence that the polycystic livers exhibit increased and accelerated differentiation of hepatoblasts into cholangiocyte precursors, eventually coalescing into large biliary cysts. Lineage tracing experiments, performed in mouse embryos, indicated that the cholangiocyte precursors in Cpk mice generate cholangiocytes and periportal hepatocytes, like in wild-type animals. Therefore, contrary to current belief, cyst formation in polycystic liver disease does not necessarily depend on overproliferation. Combining our prenatal data with available data from adult livers, we propose that polycystic liver can be initiated by proliferation-independent mechanisms at a fetal stage, followed by postnatal proliferation-dependent cyst expansion.

  12. Neuroimaging and Recovery of Language in Aphasia

    PubMed Central

    Thompson, Cynthia K.; den Ouden, Dirk-Bart

    2010-01-01

    The use of functional neuroimaging techniques has advanced what is known about the neural mechanisms used to support language processing in aphasia resulting from brain damage. This paper highlights recent findings derived from neuroimaging studies focused on neuroplasticity of language networks, the role of the left and right hemispheres in this process, and studies examining how treatment affects the neurobiology of recovery. We point out variability across studies as well as factors related to this variability, and we emphasize challenges that remain for research. PMID:18957184

  13. Model-based neuroimaging for cognitive computing.

    PubMed

    Poznanski, Roman R

    2009-09-01

    The continuity of the mind is suggested to mean the continuous spatiotemporal dynamics arising from the electrochemical signature of the neocortex: (i) globally through volume transmission in the gray matter as fields of neural activity, and (ii) locally through extrasynaptic signaling between fine distal dendrites of cortical neurons. If the continuity of dynamical systems across spatiotemporal scales defines a stream of consciousness then intentional metarepresentations as templates of dynamic continuity allow qualia to be semantically mapped during neuroimaging of specific cognitive tasks. When interfaced with a computer, such model-based neuroimaging requiring new mathematics of the brain will begin to decipher higher cognitive operations not possible with existing brain-machine interfaces.

  14. [Treatment and outcome of Crohn's disease without initial complications. Results of a retrospective, multicenter Tunisian study].

    PubMed

    Cheikh, Imed; Ben Ammar, Ahmed; Essid, Mejda; Azzouz, Messadak; Ettahri, Nabil; Krichene, Mohamed; Bouzaidi, Slim; Ennajar, Taoufik

    2002-04-01

    The purpose of this study was to estimate and achieve the factors that have an influence on the evolution of the Chron's disease. This study was done in 124 patients reaching the diagnosis of Chron's disease between 1988 and 1997. The evolution of this disease was achieved in 87 patients. The Chron's disease was inactive among 31 patients (35-6%)--with discontinous evolution in 42 patients (48.3%) and active chronic in 14 patients (16-1%). The active chronic form of Chron's disease was twice more frequent among the smokers and the patients with age above 40 years--but this difference has no statistical significance. The indication of surgical treatment was realised in 21 patients and it takes place as result of failure of medical treatment in 16 patients (76-2%)--an abcess in 2 patents (9-5%) and iatrogenic perforation in 1 patient (4-8%). The age-sexe-smoke--the intensity of the initial attack and the nature of the treatment had no influence in the need of the surgical interfference. The Chron's disease showed the less severe evolution in this study--the age above 40 years and the consumption of smoke increased the frequency of active chronic form.

  15. Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma.

    PubMed

    Sánchez-Sánchez, Francisco; Ramírez-Castillejo, Carmen; Weekes, Daniel B; Beneyto, Magdalena; Prieto, Félix; Nájera, Carmen; Mittnacht, Sibylle

    2007-02-01

    Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait. In the majority of cases disease develops in greater than 90% of carriers. However, reduced penetrance with a large portion of disease-free carrier is seen in some families. Unambiguous identification of the predisposing mutation in these families is important for accurate risk prediction in relatives and their genetic counseling but also provides conceptual information regarding the relationship between the RB1 genotype and the disease phenotype. In this study we report a novel mutation detected in 10 individuals of an extended family, only three of whom are affected by RB disease. The mutation comprises a 23-basepair (bp) duplication in the first exon of RB1 (c.43_65dup) producing a frameshift in exon 1 and premature chain termination in exon 2. Mutations resulting in premature chain termination classically are associated with high penetrance disease, as message translation may not generate functional product and nonsense mediated RNA decay (NMD) frequently eliminates the mutant transcript. However, appreciable NMD does not follow from the mutation described here and transcript expression in tissue culture cells and translation in vitro reveals that alternative in-frame translation start sites involving Met113 and possibly Met233 are used to generate truncated RB1 products (pRB94 and pRB80), known and suspected to exhibit tumor suppressor activity. These results strongly suggest that modulation of disease penetrance in this family is achieved by internal translation initiation. Our observations provide the first example for rescue of a chain-terminating mutation in RB1 through alternative translation initiation.

  16. Loss of executive function after dialysis initiation in adults with chronic kidney disease.

    PubMed

    Kurella Tamura, Manjula; Vittinghoff, Eric; Hsu, Chi-Yuan; Tam, Karman; Seliger, Stephen L; Sozio, Stephen; Fischer, Michael; Chen, Jing; Lustigova, Eva; Strauss, Louise; Deo, Rajat; Go, Alan S; Yaffe, Kristine

    2017-04-01

    The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m(2) or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation.

  17. Perturbations of ground support alter posture and locomotion coupling during step initiation in Parkinson's disease.

    PubMed

    Rogers, Mark W; Hilliard, Marjorie Johnson; Martinez, Katherine M; Zhang, Yunhui; Simuni, Tanya; Mille, Marie-Laure

    2011-02-01

    During the initiation of stepping, anticipatory postural adjustments (APAs) for lateral weight transfer and propulsion normally precede the onset of locomotion. In Parkinson's disease (PD), impaired step initiation typically involves altered APA ground force production with delayed step onset and deficits in stepping performance. If, as in stance and gait, sensory information about lower limb load is important for the control of stepping, then perturbations influencing loading conditions could affect the step initiation process. This study investigated the influence of changes in lower limb loading during step initiation in patients with PD and healthy control subjects. Participants performed rapid self-triggered step initiation with the impending single stance limb positioned over a pneumatically actuated platform. In perturbation trials, the stance limb ground support surface was either moved vertically downward (DROP) or upward (ELEVATE) by 1.5 cm shortly after the onset of the APA phase. Overall, PD patients demonstrated a longer APA duration, longer time to first step onset, and slower step speed than controls. In both groups, the DROP perturbation reinforced the intended APA kinetic changes for lateral weight transfer and resulted in a significant reduction in APA duration, increase in peak amplitude, and earlier time to first step onset compared with other conditions. During ELEVATE trials that opposed the intended weight transfer forces both groups rapidly adapted their stepping to preserve standing stability by decreasing step length and duration, and increasing step height and foot placement laterally. The findings suggested that sensory information associated with limb load and/or foot pressure modulates the spatial and temporal parameters of posture and locomotion components of step initiation in interaction with a centrally generated feedforward mode of neural control. Moreover, impaired step initiation in PD may at least acutely be enhanced by

  18. A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

    PubMed

    Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

    2017-04-01

    After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

  19. Neuroimaging the brain-gut axis in patients with irritable bowel syndrome

    PubMed Central

    Weaver, Kristen R; Sherwin, LeeAnne B; Walitt, Brian; Melkus, Gail D’Eramo; Henderson, Wendy A

    2016-01-01

    AIM: To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome (IBS). METHODS: A database search for relevant literature was conducted using PubMed, Scopus and Embase in February 2015. Date filters were applied from the year 2009 and onward, and studies were limited to those written in the English language and those performed upon human subjects. The initial search yielded 797 articles, out of which 38 were pulled for full text review and 27 were included for study analysis. Investigations were reviewed to determine study design, methodology and results, and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations. RESULTS: Analysis of study data resulted in the abstraction of four key themes: Neurohormonal differences, anatomic measurements of brain structure and connectivity, differences in functional responsiveness of the brain during rectal distention, and confounding/correlating patient factors. Studies in this review noted alterations of glutamate in the left hippocampus (HIPP), commonalities across IBS subjects in terms of brain oscillation patterns, cortical thickness/gray matter volume differences, and neuroanatomical regions with increased activation in patients with IBS: Anterior cingulate cortex, mid cingulate cortex, amygdala, anterior insula, posterior insula and prefrontal cortex. A striking finding among interventions was the substantial influence that patient variables (e.g., sex, psychological and disease related factors) had upon the identification of neuroanatomical differences in structure and connectivity. CONCLUSION: The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population. PMID:27158548

  20. Multimodal Neuroimaging-Informed Clinical Applications in Neuropsychiatric Disorders

    PubMed Central

    O’Halloran, Rafael; Kopell, Brian H.; Sprooten, Emma; Goodman, Wayne K.; Frangou, Sophia

    2016-01-01

    Recent advances in neuroimaging data acquisition and analysis hold the promise to enhance the ability to make diagnostic and prognostic predictions and perform treatment planning in neuropsychiatric disorders. Prior research using a variety of types of neuroimaging techniques has confirmed that neuropsychiatric disorders are associated with dysfunction in anatomical and functional brain circuits. We first discuss current challenges associated with the identification of reliable neuroimaging markers for diagnosis and prognosis in mood disorders and for neurosurgical treatment planning for deep brain stimulation (DBS). We then present data on the use of neuroimaging for the diagnosis and prognosis of mood disorders and for DBS treatment planning. We demonstrate how multivariate analyses of functional activation and connectivity parameters can be used to differentiate patients with bipolar disorder from those with major depressive disorder and non-affective psychosis. We also present data on connectivity parameters that mediate acute treatment response in affective and non-affective psychosis. We then focus on precision mapping of functional connectivity in native space. We describe the benefits of integrating anatomical fiber reconstruction with brain functional parameters and cortical surface measures to derive anatomically informed connectivity metrics within the morphological context of each individual brain. We discuss how this approach may be particularly promising in psychiatry, given the clinical and etiological heterogeneity of the disorders, and particularly in treatment response prediction and planning. Precision mapping of connectivity is essential for DBS. In DBS, treatment electrodes are inserted into positions near key gray matter nodes within the circuits considered relevant to disease expression. However, targeting white matter tracts that underpin connectivity within these circuits may increase treatment efficacy and tolerability therefore relevant

  1. Multimodal Neuroimaging-Informed Clinical Applications in Neuropsychiatric Disorders.

    PubMed

    O'Halloran, Rafael; Kopell, Brian H; Sprooten, Emma; Goodman, Wayne K; Frangou, Sophia

    2016-01-01

    Recent advances in neuroimaging data acquisition and analysis hold the promise to enhance the ability to make diagnostic and prognostic predictions and perform treatment planning in neuropsychiatric disorders. Prior research using a variety of types of neuroimaging techniques has confirmed that neuropsychiatric disorders are associated with dysfunction in anatomical and functional brain circuits. We first discuss current challenges associated with the identification of reliable neuroimaging markers for diagnosis and prognosis in mood disorders and for neurosurgical treatment planning for deep brain stimulation (DBS). We then present data on the use of neuroimaging for the diagnosis and prognosis of mood disorders and for DBS treatment planning. We demonstrate how multivariate analyses of functional activation and connectivity parameters can be used to differentiate patients with bipolar disorder from those with major depressive disorder and non-affective psychosis. We also present data on connectivity parameters that mediate acute treatment response in affective and non-affective psychosis. We then focus on precision mapping of functional connectivity in native space. We describe the benefits of integrating anatomical fiber reconstruction with brain functional parameters and cortical surface measures to derive anatomically informed connectivity metrics within the morphological context of each individual brain. We discuss how this approach may be particularly promising in psychiatry, given the clinical and etiological heterogeneity of the disorders, and particularly in treatment response prediction and planning. Precision mapping of connectivity is essential for DBS. In DBS, treatment electrodes are inserted into positions near key gray matter nodes within the circuits considered relevant to disease expression. However, targeting white matter tracts that underpin connectivity within these circuits may increase treatment efficacy and tolerability therefore relevant

  2. Functional neuroimaging: technical, logical, and social perspectives.

    PubMed

    Aguirre, Geoffrey K

    2014-01-01

    Neuroscientists have long sought to study the dynamic activity of the human brain-what's happening in the brain, that is, while people are thinking, feeling, and acting. Ideally, an inside look at brain function would simultaneously and continuously measure the biochemical state of every cell in the central nervous system. While such a miraculous method is science fiction, a century of progress in neuroimaging technologies has made such simultaneous and continuous measurement a plausible fiction. Despite this progress, practitioners of modern neuroimaging struggle with two kinds of limitations: those that attend the particular neuroimaging methods we have today and those that would limit any method of imaging neural activity, no matter how powerful. In this essay, I consider the liabilities and potential of techniques that measure human brain activity. I am concerned here only with methods that measure relevant physiologic states of the central nervous system and relate those measures to particular mental states. I will consider in particular the preeminent method of functional neuroimaging: BOLD fMRI. While there are several practical limits on the biological information that current technologies can measure, these limits-as important as they are-are minor in comparison to the fundamental logical restraints on the conclusions that can be drawn from brain imaging studies.

  3. The open-source neuroimaging research enterprise.

    PubMed

    Marcus, Daniel S; Archie, Kevin A; Olsen, Timothy R; Ramaratnam, Mohana

    2007-11-01

    While brain imaging in the clinical setting is largely a practice of looking at images, research neuroimaging is a quantitative and integrative enterprise. Images are run through complex batteries of processing and analysis routines to generate numeric measures of brain characteristics. Other measures potentially related to brain function - demographics, genetics, behavioral tests, neuropsychological tests - are key components of most research studies. The canonical scanner - PACS - viewing station axis used in clinical practice is therefore inadequate for supporting neuroimaging research. Here, we model the neuroimaging research enterprise as a workflow. The principal components of the workflow include data acquisition, data archiving, data processing and analysis, and data utilization. We also describe a set of open-source applications to support each step of the workflow and the transitions between these steps. These applications include DIGITAL IMAGING AND COMMUNICATIONS IN MEDICINE viewing and storage tools, the EXTENSIBLE NEUROIMAGING ARCHIVE TOOLKIT data archiving and exploration platform, and an engine for running processing/analysis pipelines. The overall picture presented is aimed to motivate open-source developers to identify key integration and communication points for interoperating with complimentary applications.

  4. Neuroimaging studies of social cognition in schizophrenia.

    PubMed

    Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya

    2015-05-01

    Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology.

  5. Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease.

    PubMed

    Qian, Ye; Culton, Donna A; Jeong, Joseph S; Trupiano, Nicole; Valenzuela, Jesus G; Diaz, Luis A

    2016-09-01

    Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.

  6. Neuroimaging of Lipid Storage Disorders

    ERIC Educational Resources Information Center

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  7. Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative.

    PubMed

    Borrow, Ray; Lee, Jin-Soo; Vázquez, Julio A; Enwere, Godwin; Taha, Muhamed-Kheir; Kamiya, Hajime; Kim, Hwang Min; Jo, Dae Sun

    2016-11-21

    The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014. The GMI reviewed the epidemiology of MD, surveillance, and prevention strategies, and outbreak control practices from participating countries in the Asia-Pacific region.Although, in general, MD is underreported in this region, serogroup A disease is most prominent in low-income countries such as India and the Philippines, while Taiwan, Japan, and Korea reported disease from serogroups C, W, and Y. China has a mixed epidemiology of serogroups A, B, C, and W. Perspectives from countries outside of the region were also provided to provide insight into lessons learnt. Based on the available data and meeting discussions, a number of challenges and data gaps were identified and, as a consequence, several recommendations were formulated: strengthen surveillance; improve diagnosis, typing and case reporting; standardize case definitions; develop guidelines for outbreak management; and promote awareness of MD among healthcare professionals, public health officials, and the general public.

  8. The impact of birth weight on cardiovascular disease risk in the Women's Health Initiative

    PubMed Central

    Smith, CJ; Ryckman, KK; Barnabei, Vanessa M.; Howard, Barbara; Isasi, Carmen R.; Sarto, Gloria; Tom, Sarah E.; Van Horn, Linda; Wallace, Robert; Robinson, Jennifer G

    2016-01-01

    Background and Aims Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction. Methods and Results The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63 815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (< 6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR=1.086, p=0.009). LBW was a significant covariate in the BMI-based model (HR=1.128, p<0.0001) but not in the lipid-based models. Conclusion LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease. PMID:26708645

  9. Heritability and Genetic Association Analysis of Neuroimaging Measures in the Diabetes Heart Study

    PubMed Central

    Raffield, Laura M; Cox, Amanda J; Hugenschmidt, Christina E; Freedman, Barry I; Langefeld, Carl D; Williamson, Jeff D; Hsu, Fang-Chi; Maldjian, Joseph A; Bowden, Donald W

    2014-01-01

    Patients with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Neuroimaging measures such as white matter lesion volume, brain volume, and fractional anisotropy may reflect the pathogenesis of these cognitive declines, and genetic factors may contribute to variability in these measures. This study examined multiple neuroimaging measures in 465 participants from 238 families with extensive genotype data in the type 2 diabetes enriched Diabetes Heart Study-Mind cohort. Heritability of these phenotypes and their association with candidate single nucleotide polymorphisms (SNPs) and SNP data from genome-and exome-wide arrays was explored. All neuroimaging measures analysed were significantly heritable (ĥ2 =0.55–0.99 in unadjusted models). Seventeen candidate SNPs (from 16 genes/regions) associated with neuroimaging phenotypes in prior studies showed no significant evidence of association. A missense variant (rs150706952, A432V) in PLEKHG4B from the exome-wide array was significantly associated with white matter mean diffusivity (p=3.66×10−7) and gray matter mean diffusivity (p=2.14×10−7). This analysis suggests genetic factors contribute to variation in neuroimaging measures in a population enriched for metabolic disease and other associated comorbidities. PMID:25523635

  10. Sparse kernel entropy component analysis for dimensionality reduction of neuroimaging data.

    PubMed

    Jiang, Qikun; Shi, Jun

    2014-01-01

    The neuroimaging data typically has extremely high dimensions. Therefore, dimensionality reduction is commonly used to extract discriminative features. Kernel entropy component analysis (KECA) is a newly developed data transformation method, where the key idea is to preserve the most estimated Renyi entropy of the input space data set via a kernel-based estimator. Despite its good performance, KECA still suffers from the problem of low computational efficiency for large-scale data. In this paper, we proposed a sparse KECA (SKECA) algorithm with the recursive divide-and-conquer based solution, and then applied it to perform dimensionality reduction of neuroimaging data for classification of the Alzheimer's disease (AD). We compared the SKECA with KECA, principal component analysis (PCA), kernel PCA (KPCA) and sparse KPCA. The experimental results indicate that the proposed SKECA has most superior performance to all other algorithms when extracting discriminative features from neuroimaging data for AD classification.

  11. Mind-Body Practices and the Adolescent Brain: Clinical Neuroimaging Studies

    PubMed Central

    Sharma, Anup; Newberg, Andrew B

    2016-01-01

    Background Mind-Body practices constitute a large and diverse group of practices that can substantially affect neurophysiology in both healthy individuals and those with various psychiatric disorders. In spite of the growing literature on the clinical and physiological effects of mind-body practices, very little is known about their impact on central nervous system (CNS) structure and function in adolescents with psychiatric disorders. Method This overview highlights findings in a select group of mind-body practices including yoga postures, yoga breathing techniques and meditation practices. Results Mind-body practices offer novel therapeutic approaches for adolescents with psychiatric disorders. Findings from these studies provide insights into the design and implementation of neuroimaging studies for adolescents with psychiatric disorders. Conclusions Clinical neuroimaging studies will be critical in understanding how different practices affect disease pathogenesis and symptomatology in adolescents. Neuroimaging of mind-body practices on adolescents with psychiatric disorders will certainly be an open and exciting area of investigation. PMID:27347478

  12. Tubulointerstitial Nephritis as the Initial Presentation of Crohn’s Disease and Successful Treatment with Infliximab

    PubMed Central

    Caza, Tiffany; Huang, Dongmei; Beg, Mirza B.

    2017-01-01

    Tubulointerstitial nephritis (TIN) is not commonly associated in aminosalicylate-naïve patients with Crohn’s disease (CD). Our case describes the initial presentation, diagnosis, and management of an adolescent presenting with TIN and underlying CD. Our case emphasizes that CD should be considered in the differential diagnosis of interstitial nephritis as not only a medication-related effect, but also as an extraintestinal manifestation of CD. We also describe successful management of undiagnosed recurring and symptomatic CD-related TIN with infliximab. PMID:28286790

  13. Pulmonary Nodules as an Initial Manifestation of Behçet's Disease

    PubMed Central

    Malekmohammad, M.; Emamifar, A.

    2014-01-01

    Behçet's disease (BD) is a systemic vasculopathy, characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions. Although vascular involvement, including venous and arteries of any size, is a usual manifestation, cases with pulmonary thrombosis as the initial symptom are not common in the absence of pulmonary artery aneurysm (PAA). This report describes a 36-year-old man with recurrent fever, nonmassive hemoptysis, and persistent cough with lung nodules in CT scan who had undergone open lung biopsy. On the basis of morphological findings, BD was suggested and more precise evaluation confirmed the diagnosis. PMID:25436168

  14. Chylothorax and chylopericardium as the initial clinical manifestation of Behcet's disease.

    PubMed

    Moon, H; Lee, Y J; Lee, S I; Yoo, W H

    2008-02-01

    Behcet's disease (BD) is a chronic relapsing systemic vasculitic disorder affecting the arteries, veins, and vessels of any size. Large vein thrombosis in BD is not commonly developed and most commonly observed in the veins in the lower extremities and inferior or superior vena cava. In this report, a 18-year-old male patient with large vein thrombosis involving superior vena cava was presented. He was treated due to chylothorax and chylopericardium with SVC syndrome before diagnosis of BD. SVC thrombosis complicated by chylothorax and chyolpericardium can be a rare presenting initial symptom of BD.

  15. Moving forward with prisms: sensory-motor adaptation improves gait initiation in Parkinson's disease.

    PubMed

    Bultitude, Janet H; Rafal, Robert D; Tinker, Corinne

    2012-01-01

    It is postulated that the decreased walking speed; small, shuffling steps; and "freezing" shown by patients with Parkinson's disease could stem from an inability to tilt the body forward enough to provide sufficient forward propulsion. In two repeated-measures studies we examined whether adaptation to upward-shifting prisms, resulting in a downward after-effect, could improve gait initiation in healthy participants and patients with Parkinson's disease. Faster forward stepping followed a brief (5 min) exposure period for patients, and a longer (20 min) exposure period for age-matched controls. Backward stepping was unchanged, and adaptation to downward-shifting prisms with control participants showed no effect on forward or backward stepping. These results suggest that adaptation of arm proprioception in the vertical plane may generalize to anterior-posterior postural control, presenting new possibilities for the treatment of gait disturbance in basal ganglia disorders.

  16. Calcium in the initiation, progression and as an effector of Alzheimer’s disease pathology

    PubMed Central

    Green, Kim N

    2009-01-01

    The cause(s) of sporadic Alzheimer’s disease (sAD) are complex and currently poorly understood. They likely result from a combination of genetic, environmental, proteomic and lipidomic factors that crucially occur only in the aged brain. Age-related changes in calcium levels and dynamics have the potential to increase the production and accumulation of both amyloid-β peptide (Aβ) and τ pathologies in the AD brain, although these two pathologies themselves can induce calcium dyshomeostasis, particularly at synaptic membranes. This review discuses the evidence for a role for calcium dyshomeostasis in the initiation of pathology, as well as the evidence for these pathologies themselves disrupting normal calcium homeostasis, which lead to synaptic and neuronal dysfunction, synaptotoxicity and neuronal loss, underlying the dementia associated with the disease. PMID:19650832

  17. Neuromarketing: the hope and hype of neuroimaging in business.

    PubMed

    Ariely, Dan; Berns, Gregory S

    2010-04-01

    The application of neuroimaging methods to product marketing - neuromarketing - has recently gained considerable popularity. We propose that there are two main reasons for this trend. First, the possibility that neuroimaging will become cheaper and faster than other marketing methods; and second, the hope that neuroimaging will provide marketers with information that is not obtainable through conventional marketing methods. Although neuroimaging is unlikely to be cheaper than other tools in the near future, there is growing evidence that it may provide hidden information about the consumer experience. The most promising application of neuroimaging methods to marketing may come before a product is even released - when it is just an idea being developed.

  18. Systematic Review of Structural and Functional Neuroimaging Findings in Children and Adults with CKD

    PubMed Central

    Reiser, Kathryn A.; Detre, John A.; Schultz, Robert T.; Herrington, John D.; Davatzikos, Christos; Doshi, Jimit J.; Erus, Guray; Liu, Hua-Shan; Radcliffe, Jerilynn; Furth, Susan L.; Hooper, Stephen R.

    2013-01-01

    Summary CKD has been linked with cognitive deficits and affective disorders in multiple studies. Analysis of structural and functional neuroimaging in adults and children with kidney disease may provide additional important insights into the pathobiology of this relationship. This paper comprehensively reviews neuroimaging studies in both children and adults. Major databases (PsychLit, MEDLINE, WorldCat, ArticleFirst, PubMed, Ovid MEDLINE) were searched using consistent search terms, and studies published between 1975 and 2012 were included if their samples focused on CKD as the primary disease process. Exclusion criteria included case reports, chapters, and review articles. This systematic process yielded 43 studies for inclusion (30 in adults, 13 in children). Findings from this review identified several clear trends: (1) presence of cerebral atrophy and cerebral density changes in patients with CKD; (2) cerebral vascular disease, including deep white matter hyperintensities, white matter lesions, cerebral microbleeds, silent cerebral infarction, and cortical infarction, in patients with CKD; and (3) similarities in regional cerebral blood flow between patients with CKD and those with affective disorders. These findings document the importance of neuroimaging procedures in understanding the effect of CKD on brain structure, function, and associated behaviors. Results provide a developmental linkage between childhood and adulthood, with respect to the effect of CKD on brain functioning across the lifespan, with strong implications for a cerebrovascular mechanism contributing to this developmental linkage. Use of neuroimaging methods to corroborate manifest neuropsychological deficits or perhaps to indicate preventive actions may prove useful to individuals with CKD. PMID:23723341

  19. Systematic review of structural and functional neuroimaging findings in children and adults with CKD.

    PubMed

    Moodalbail, Divya G; Reiser, Kathryn A; Detre, John A; Schultz, Robert T; Herrington, John D; Davatzikos, Christos; Doshi, Jimit J; Erus, Guray; Liu, Hua-Shan; Radcliffe, Jerilynn; Furth, Susan L; Hooper, Stephen R

    2013-08-01

    CKD has been linked with cognitive deficits and affective disorders in multiple studies. Analysis of structural and functional neuroimaging in adults and children with kidney disease may provide additional important insights into the pathobiology of this relationship. This paper comprehensively reviews neuroimaging studies in both children and adults. Major databases (PsychLit, MEDLINE, WorldCat, ArticleFirst, PubMed, Ovid MEDLINE) were searched using consistent search terms, and studies published between 1975 and 2012 were included if their samples focused on CKD as the primary disease process. Exclusion criteria included case reports, chapters, and review articles. This systematic process yielded 43 studies for inclusion (30 in adults, 13 in children). Findings from this review identified several clear trends: (1) presence of cerebral atrophy and cerebral density changes in patients with CKD; (2) cerebral vascular disease, including deep white matter hyperintensities, white matter lesions, cerebral microbleeds, silent cerebral infarction, and cortical infarction, in patients with CKD; and (3) similarities in regional cerebral blood flow between patients with CKD and those with affective disorders. These findings document the importance of neuroimaging procedures in understanding the effect of CKD on brain structure, function, and associated behaviors. Results provide a developmental linkage between childhood and adulthood, with respect to the effect of CKD on brain functioning across the lifespan, with strong implications for a cerebrovascular mechanism contributing to this developmental linkage. Use of neuroimaging methods to corroborate manifest neuropsychological deficits or perhaps to indicate preventive actions may prove useful to individuals with CKD.

  20. Initial and long-term costs of patients hospitalized with West Nile virus disease.

    PubMed

    Staples, J Erin; Shankar, Manjunath B; Sejvar, James J; Meltzer, Martin I; Fischer, Marc

    2014-03-01

    There are no published data on the economic burden for specific West Nile virus (WNV) clinical syndromes (i.e., fever, meningitis, encephalitis, and acute flaccid paralysis [AFP]). We estimated initial hospital and lost-productivity costs from 80 patients hospitalized with WNV disease in Colorado during 2003; 38 of these patients were followed for 5 years to determine long-term medical and lost-productivity costs. Initial costs were highest for patients with AFP (median $25,117; range $5,385-$283,381) and encephalitis (median $20,105; range $3,965-$324,167). Long-term costs were highest for patients with AFP (median $22,628; range $624-$439,945) and meningitis (median $10,556; range $0-$260,748). Extrapolating from this small cohort to national surveillance data, we estimated the total cumulative costs of reported WNV hospitalized cases from 1999 through 2012 to be $778 million (95% confidence interval $673 million-$1.01 billion). These estimates can be used in assessing the cost-effectiveness of interventions to prevent WNV disease.

  1. The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases.

    PubMed

    Rabaa, Maia A; Tue, Ngo Tri; Phuc, Tran My; Carrique-Mas, Juan; Saylors, Karen; Cotten, Matthew; Bryant, Juliet E; Nghia, Ho Dang Trung; Cuong, Nguyen Van; Pham, Hong Anh; Berto, Alessandra; Phat, Voong Vinh; Dung, Tran Thi Ngoc; Bao, Long Hoang; Hoa, Ngo Thi; Wertheim, Heiman; Nadjm, Behzad; Monagin, Corina; van Doorn, H Rogier; Rahman, Motiur; Tra, My Phan Vu; Campbell, James I; Boni, Maciej F; Tam, Pham Thi Thanh; van der Hoek, Lia; Simmonds, Peter; Rambaut, Andrew; Toan, Tran Khanh; Van Vinh Chau, Nguyen; Hien, Tran Tinh; Wolfe, Nathan; Farrar, Jeremy J; Thwaites, Guy; Kellam, Paul; Woolhouse, Mark E J; Baker, Stephen

    2015-12-01

    The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to

  2. Molecular neuroimaging in rodents: assessing receptor expression and function.

    PubMed

    Mueggler, Thomas; Baltes, Christof; Rudin, Markus

    2009-11-01

    Multimodal non-invasive neuroimaging in rodents constitutes an attractive tool for studying neurobiological processes in vivo. At present, imaging studies of brain anatomy and function as well as the investigation of structure-function relationships belong to the standard repertoire of neuroscientists. Molecular imaging adds a new perspective. The mapping of the receptor distribution and receptor occupancy can nowadays be complemented by specific readouts of receptor function either by visualizing the activity of signaling pathways or mapping the physiological consequences of receptor stimulation. Molecular information is obtained through the use of imaging probes that combine a target-specific ligand with a reporter moiety that generates a signal that can be detected from outside the body. For imaging probes targeting the central nervous system, penetration of the intact blood-brain barrier constitutes a major hurdle. Molecular imaging generates specific information and therefore has a large potential for disease phenotyping (diagnostics), therapy development and monitoring of treatment response. Molecular imaging is still in its infancy and major developments in imaging technology, probe design and data analysis are required in order to make an impact. Rodent molecular neuroimaging will play an important role in the development of these tools.

  3. Disease-modifying drug initiation patterns in commercially insured multiple sclerosis patients: a retrospective cohort study

    PubMed Central

    2011-01-01

    Background The goal of this research was to compare the demographics, clinical characteristics and treatment patterns for newly diagnosed multiple sclerosis (MS) patients in a commercial managed care population who received disease-modifying drug (DMD) therapy versus those not receiving DMD therapy. Methods A retrospective cohort study using US administrative healthcare claims identified individuals newly diagnosed with MS (no prior MS diagnosis 12 months prior using ICD-9-CM 340) and ≥ 18 years old during 2001-2007 to characterize them based on demographics, clinical characteristics, and pharmacologic therapy for one year prior to and a minimum of one year post-index. The index date was the first MS diagnosis occurring in the study period. Follow-up of subjects was done by ICD-9-CM code identification and not by actual chart review. Multivariate analyses were conducted to adjust for confounding variables. Results Patients were followed for an average of 35.7 ± 17.5 months after their index diagnosis. Forty-three percent (n = 4,462) of incident patients received treatment with at least one of the DMDs during the post-index period. Treated patients were primarily in the younger age categories of 18-44 years of age, with DMD therapy initiated an average of 5.3 ± 9.1 months after the index diagnosis. Once treatment was initiated, 27.7% discontinued DMD therapy after an average of 17.6 ± 14.6 months, and 16.5% had treatment gaps in excess of 60 days. Conclusions Nearly 60% of newly-diagnosed MS patients in this commercial managed care population remained untreated while over a quarter of treated patients stopped therapy and one-sixth experienced treatment gaps despite the risk of disease progression or a return of pre-treatment disease activity. PMID:21974973

  4. Neuroimage evidence and the insanity defense.

    PubMed

    Schweitzer, N J; Saks, Michael J

    2011-01-01

    The introduction of neuroscientific evidence in criminal trials has given rise to fears that neuroimagery presented by an expert witness might inordinately influence jurors' evaluations of the defendant. In this experiment, a diverse sample of 1,170 community members from throughout the U.S. evaluated a written mock trial in which psychological, neuropsychological, neuroscientific, and neuroimage-based expert evidence was presented in support of a not guilty by reason of insanity (NGRI) defense. No evidence of an independent influence of neuroimagery was found. Overall, neuroscience-based evidence was found to be more persuasive than psychological and anecdotal family history evidence. These effects were consistent across different insanity standards. Despite the non-influence of neuroimagery, however, jurors who were not provided with a neuroimage indicated that they believed neuroimagery would have been the most helpful kind of evidence in their evaluations of the defendant.

  5. Deep learning for neuroimaging: a validation study.

    PubMed

    Plis, Sergey M; Hjelm, Devon R; Salakhutdinov, Ruslan; Allen, Elena A; Bockholt, Henry J; Long, Jeffrey D; Johnson, Hans J; Paulsen, Jane S; Turner, Jessica A; Calhoun, Vince D

    2014-01-01

    Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager's toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building block the restricted Boltzmann machine. We also describe a novel constraint-based approach to visualizing high dimensional data. We use it to analyze the effect of parameter choices on data transformations. Our results show that deep learning methods are able to learn physiologically important representations and detect latent relations in neuroimaging data.

  6. Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

    PubMed Central

    Makimoto, Go; Manabe, Yasuhiro; Yamakawa, Chizuru; Fujii, Daiki; Ikeda-Sakai, Yasuko; Narai, Hisashi; Omori, Nobuhiko; Abe, Koji

    2012-01-01

    We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR), magnetic resonance imaging (MRI) and diffusion-weighted images (DWI) showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions. PMID:22593809

  7. [The control of the transmission by transfusion of Chagas' disease in the Southern Cone Initiative].

    PubMed

    Dias, J C; Schofield, C J

    1998-01-01

    The Southern Cone Initiative against Chagas' disease, was launched in 1991. The aim was to interrupt the transmission of Chagas disease by elimination of domestic populations of the major vector, Triatoma infestans, and by improved screening of blood donors. As a result of these activities, a marked reduction in the risk of transfusional transmission can now be seen throughout the programme area. In addition to specific legislation concerning the quality of transfused blood, a series of national and regional reference laboratories have been set up with the help of PAHO in order to improve the quality of pre-transfusional serodiagnosis. Results indicate a progressive reduction in the overall infection prevalence of blood donors, and show that the age-prevalence curve has shifted towards older age-groups. In this paper we analyse the changes in infection prevalence in the Southern Cone countries, drawing attention to the situation in Bolivia which has the highest indices of infection and lowest levels of coverage by the control programme. In this situation chemoprophylaxis of blood prior to transfusion may be recommended in accordance with PAHO criteria. In the medium term however, interruption of human Chagas disease transmission may be expected over most of the Southern Cone region, as long as the control activities are continued and consolidated through effective epidemiological surveillance.

  8. Adrenal medullary transplantation to the caudate nucleus in Parkinson's disease. Initial clinical results in 18 patients.

    PubMed

    Allen, G S; Burns, R S; Tulipan, N B; Parker, R A

    1989-05-01

    Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

  9. Clinical Predictors of Diagnostic Testing Utility in the Initial Evaluation of Chronic Kidney Disease

    PubMed Central

    Mendu, Mallika L.; Lundquist, Andrew; Aizer, Ayal A.; Leaf, David E.; Robinson, Emily; Steele, David J.R.; Waikar, Sushrut S.

    2016-01-01

    Aim No evidence-based approach to the evaluation of CKD has been established. We sought to identify clinical criteria to guide a rational diagnostic approach for the initial evaluation of CKD. Methods We conducted a retrospective cohort study of 1,487 patients presenting for initial evaluation of CKD over three years (1/2010–1/2013) to academic nephrology clinics. We utilized the electronic medical record to determine tests ordered, abnormal results, and testing that affected diagnosis and/or management. Diagnostic and management yield of testing was defined as the percentage of tests that affected diagnosis and/or management. High yield for a given test was defined as an increased likelihood of the test affecting diagnosis and/or management. Results We identified clinical criteria predictive of high yield for paraprotein-related testing (one of the following: history of monoclonal disease, high risk of CKD progression, hypercalcemia or hemoglobin <10.6), and clinical criteria predictive of high yield for glomerulonephritis testing (one of the following: abnormal urine sediment, 3+ or greater hematuria or proteinuria >500mg/gm). A prior history of hydronephrosis and renal artery stenosis was predictive of high yield of abnormal renal ultrasound. Higher yield of testing was associated with higher risk progression categories for ANA, SPEP, urine sediment, calcium, PTH, hemoglobin, iron, and ferritin. We estimate that initial CKD evaluation costs range from $28 to $109 million/year in US-Medicare expenditure. Conclusion Numerous tests without significant clinical utility are obtained in initial CKD evaluation. Identifying criteria that can guide diagnostic testing may lead to a more informed and cost-effective approach to evaluation. PMID:26610178

  10. Human auditory neuroimaging of intensity and loudness.

    PubMed

    Uppenkamp, Stefan; Röhl, Markus

    2014-01-01

    The physical intensity of a sound, usually expressed in dB on a logarithmic ratio scale, can easily be measured using technical equipment. Loudness is the perceptual correlate of sound intensity, and is usually determined by means of some sort of psychophysical scaling procedure. The interrelation of sound intensity and perceived loudness is still a matter of debate, and the physiological correlate of loudness perception in the human auditory pathway is not completely understood. Various studies indicate that the activation in human auditory cortex is more a representation of loudness sensation rather than of physical sound pressure level. This raises the questions (1), at what stage or stages in the ascending auditory pathway is the transformation of the physical stimulus into its perceptual correlate completed, and (2), to what extent other factors affecting individual loudness judgements might modulate the brain activation as registered by auditory neuroimaging. An overview is given about recent studies on the effects of sound intensity, duration, bandwidth and individual hearing status on the activation in the human auditory system, as measured by various approaches in auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

  11. Neuroimaging: beginning to appreciate its complexities.

    PubMed

    Parens, Erik; Johnston, Josephine

    2014-01-01

    For over a century, scientists have sought to see through the protective shield of the human skull and into the living brain. Today, an array of technologies allows researchers and clinicians to create astonishingly detailed images of our brain's structure as well as colorful depictions of the electrical and physiological changes that occur within it when we see, hear, think and feel. These technologies-and the images they generate-are an increasingly important tool in medicine and science. Given the role that neuroimaging technologies now play in biomedical research, both neuroscientists and nonexperts should aim to be as clear as possible about how neuroimages are made and what they can-and cannot-tell us. Add to this that neuroimages have begun to be used in courtrooms at both the determination of guilt and sentencing stages, that they are being employed by marketers to refine advertisements and develop new products, that they are being sold to consumers for the diagnosis of mental disorders and for the detection of lies, and that they are being employed in arguments about the nature (or absence) of powerful concepts like free will and personhood, and the need for citizens to have a basic understanding of how this technology works and what it can and cannot tell us becomes even more pressing.

  12. Advanced Neuroimaging in Traumatic Brain Injury

    PubMed Central

    Edlow, Brian L.; Wu, Ona

    2013-01-01

    Advances in structural and functional neuroimaging have occurred at a rapid pace over the past two decades. Novel techniques for measuring cerebral blood flow, metabolism, white matter connectivity, and neural network activation have great potential to improve the accuracy of diagnosis and prognosis for patients with traumatic brain injury (TBI), while also providing biomarkers to guide the development of new therapies. Several of these advanced imaging modalities are currently being implemented into clinical practice, whereas others require further development and validation. Ultimately, for advanced neuroimaging techniques to reach their full potential and improve clinical care for the many civilians and military personnel affected by TBI, it is critical for clinicians to understand the applications and methodological limitations of each technique. In this review, we examine recent advances in structural and functional neuroimaging and the potential applications of these techniques to the clinical care of patients with TBI. We also discuss pitfalls and confounders that should be considered when interpreting data from each technique. Finally, given the vast amounts of advanced imaging data that will soon be available to clinicians, we discuss strategies for optimizing data integration, visualization and interpretation. PMID:23361483

  13. Sports concussions and aging: a neuroimaging investigation.

    PubMed

    Tremblay, Sebastien; De Beaumont, Louis; Henry, Luke C; Boulanger, Yvan; Evans, Alan C; Bourgouin, Pierre; Poirier, Judes; Théoret, Hugo; Lassonde, Maryse

    2013-05-01

    Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

  14. Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy

    PubMed Central

    Migita, Kiyoshi; Iwanaga, Nozomi; Imadachi, Shunsuke; Jiuchi, Yuka; Izumi, Yasumori; Tsuji, Yoshika; Kawahara, Chieko; Kawakami, Atsushi; Furukawa, Hiroshi; Tohma, Shigeto

    2015-01-01

    Abstract Few data are available regarding vertebral fracture risk in patients treated with corticosteroids including patients with interstitial lung disease (ILD). The aim of the present study was to identify risk factors for symptomatic vertebral fracture analyzed in patients with newly diagnosed autoimmune diseases. This was an observational cohort study conducted in the National Hospital Organization-EBM study group from 2006 to 2008. The study subjects were autoimmune disease patients who were newly treated with glucocorticoids (GCs). The primary endpoint was the first occurrence of vertebral fracture diagnosed by x-rays. Cox proportional-hazards regression was used to determine independent risk factors for vertebral fracture with covariates including sex, age, comorbidity, laboratory data, use of immunosuppressants, and dose of GCs. Survival was analyzed according to the Kaplan–Meier method and assessed by the log-rank test. Among 604 patients of mean age 59.5 years and mean GC dose 50.4 mg/d (first 1 months), 19 patient (3.1%) had at least 1 symptomatic vertebral fracture during 1.9 years of follow-up period. Cox regression model demonstrated that the relative risk for symptomatic vertebral fracture was independently higher in patient with ILD (hazard ratio [HR] = 2.86, 95% confidence interval [CI] = 1.10–7.42, P = 0.031) and in every 10-year increment of the age of disease onset (HR = 1.57, 95% CI = 1.09–2.26, P = 0.015). Kaplan–Meier analyses demonstrated that the incidence of vertebral fractures in patients with ILD was significantly higher in comparison with those without ILD. Our results indicate a higher risk of vertebral facture in patients with ILD and elderly patients during the initial GC treatment against autoimmune diseases. There is a need for further, even longer-term, prospective studies subjected patients with autoimmune disease, including ILD, under GC treatment. PMID:26166127

  15. The Impact of a Community-Based Chronic Disease Prevention Initiative: Evaluation Findings from "Steps to Health King County"

    ERIC Educational Resources Information Center

    Cheadle, Allen; Bourcier, Emily; Krieger, James; Beery, William; Smyser, Michael; Vinh, Diana V.; Lessler, Dan; Alfonsi, Lorrie

    2011-01-01

    "Steps to Health King County" ("Steps KC"; Seattle, Washington) was one of 40 community-level initiatives funded in 2003 as part of the "Steps to a HealthierUS" initiative. "Steps KC" goals included reducing the impact of chronic diseases through a comprehensive, coordinated approach and reducing health…

  16. [Juvenile Parkinson's disease initially presenting as bulbar incoordination: a case report].

    PubMed

    Kon, K; Sakuragawa, N; Kurokawa, T

    1994-05-01

    We report a case of juvenile Parkinson's disease which initially presented as bulbar incoordination at the age 12. The condition was characterized by dystonia of the upper extremities. The patient was a 14-year-old female. The patient's main symptoms were bulbar dysfunction. Resting and action tremor, akinesia, stooped posture, distortion of the trunk, dystonia of the upper extremities, oculogyric crisis, and impairment of the postural reflex were seen. The bulbar symptoms were considered to be attributable to circumoral uncoordination. Although L-dopa decarboxylase inhibitors were markedly effective in alleviating these symptoms, an adverse reaction due to the agent was observed as the form of oral dyskinesia. Since the changes in blood concentration of L-dopa after administration of the agent was clearly reflected in the surface electromyogram, we concluded that this diagnostic procedure is useful in evaluating the therapeutic efficacy of L-dopa.

  17. Initiation of reflective frames in counseling for Huntingtons Disease predictive testing.

    PubMed

    Sarangi, Srikant; Bennert, Kristina; Howell, Lucy; Clarke, Angus; Harper, Peter; Gray, Jonathon

    2004-04-01

    Genetic professionals and clients are likely to assign different meanings to the extended format of the counseling protocols for predictive testing. In order to facilitate informed, client-centered decisions about the possibility of predictive testing, counselors routinely use the question format to initiate what we call "reflective frames" that invite clients to discuss their feelings and encourage them to adopt introspective and self-reflective stances toward their own experience--spanning the past, the present, and the hypothetical future. We suggest that such initiations of reflective frames constitute a key element of counselors' nondirective stance, although the exact nature of their formulations can be complex and varied. Examining 24 Huntington's Disease (HD) clinic sessions involving 12 families in South Wales with the tools of discourse analysis, our focus in this paper is twofold: (i) to propose a classification of six types of reflective questions (e.g. nonspecific invites, awareness and anxiety, decision about testing, impact of result, dissemination, and other) and to examine their distribution across the various clinic appointments, and (ii) to investigate the scope of these questions in terms of temporal and social axes. We link our analysis to the current debate within the genetic counseling profession about the merits of reflection- versus information-focused counseling styles and the need to abide by professionally warranted and institutionally embedded counseling protocols.

  18. Is tree loss associated with cardiovascular-disease risk in the Women's Health Initiative? A natural experiment.

    PubMed

    Donovan, Geoffrey H; Michael, Yvonne L; Gatziolis, Demetrios; Prestemon, Jeffrey P; Whitsel, Eric A

    2015-11-01

    Data from the Women's Health Initiative were used to quantify the relationship between the loss of trees to an invasive forest pest-the emerald ash borer-and cardiovascular disease. We estimated a semi-parametric Cox proportional hazards model of time to cardiovascular disease, adjusting for confounders. We defined the incidence of cardiovascular disease as acute myocardial infarction requiring overnight hospitalization, silent MI determined from serial electrocardiograms, ischemic or hemorrhagic stroke, or death from coronary heart disease. Women living in a county infested with emerald ash borer had an increased risk of cardiovascular disease (HR=1.25, 95% CI: 1.20-1.31).

  19. Recovery from Multiple APAs Delays Gait Initiation in Parkinson’s Disease

    PubMed Central

    Cohen, Rajal G.; Nutt, John G.; Horak, Fay B.

    2017-01-01

    Background: Freezing of gait in Parkinson’s disease (PD) has been linked with deficits in inhibitory control, but causal mechanisms are not established. Freezing at gait initiation (start hesitation) is often accompanied by multiple anticipatory postural adjustments (APAs). If inhibition deficits contribute to freezing by interfering with ability to inhibit initial weight shifts in the wrong direction, then PD subjects should experience more episodes of multiple APAs than healthy controls (HCs) do. If inhibition deficits contribute to freezing by interfering with ability to release a previously inhibited step following multiple APAs, then step onset following multiple APAs should be delayed more in people with PD than in HCs. Methods: Older adults with PD and HC subjects rapidly initiated stepping in response to a light cue in blocks of simple (SRT) and choice (CRT) conditions. We recorded kinematics and ground reaction forces, and we administered the Stroop task to assess inhibitory control. Results: Multiple APAs were more common in CRT than SRT conditions but were equally common in HC and PD subjects. Step onsets were delayed in both conditions and further delayed in trials with multiple APAs, except for HC subjects in SRT trials. Poor Stroop performance correlated with many multiple APAs, late step onset, and rearward position of center of mass (COM) at cue presentation. Forward motion of the COM during the APA was higher in trials with multiple APAs than in trials with single APAs, especially in CRT trials and in PD subjects without self-reported freezing. Conclusion: Start hesitation is not caused by multiple APAs per se, but may be associated with difficulty recovering from multiple APAs, due to difficulty releasing a previously inhibited step. PMID:28261073

  20. Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease

    PubMed Central

    Ioanou, Chidima; Plassmeyer, Matthew; Ryherd, Mark; Kozhaya, Lina; Austin, Lauren; Abidoglu, Cem; Unutmaz, Derya; Alpan, Oral; Goker-Alpan, Ozlem

    2016-01-01

    Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients. PMID:27942037

  1. Executive Functioning in Daily Life in Parkinson's Disease: Initiative, Planning and Multi-Task Performance

    PubMed Central

    Koerts, Janneke; Van Beilen, Marije; Tucha, Oliver; Leenders, Klaus L.; Brouwer, Wiebo H.

    2011-01-01

    Impairments in executive functioning are frequently observed in Parkinson's disease (PD). However, executive functioning needed in daily life is difficult to measure. Considering this difficulty the Cognitive Effort Test (CET) was recently developed. In this multi-task test the goals are specified but participants are free in their approach. This study applies the CET in PD patients and investigates whether initiative, planning and multi-tasking are associated with aspects of executive functions and psychomotor speed. Thirty-six PD patients with a mild to moderate disease severity and thirty-four healthy participants were included in this study. PD patients planned and demonstrated more sequential task execution, which was associated with a decreased psychomotor speed. Furthermore, patients with a moderate PD planned to execute fewer tasks at the same time than patients with a mild PD. No differences were found between these groups for multi-tasking. In conclusion, PD patients planned and executed the tasks of the CET sequentially rather than in parallel presumably reflecting a compensation strategy for a decreased psychomotor speed. Furthermore, patients with moderate PD appeared to take their impairments into consideration when planning how to engage the tasks of the test. This compensation could not be detected in patients with mild PD. PMID:22206004

  2. Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease.

    PubMed

    Dufek, Brianna; Meehan, Daniel T; Delimont, Duane; Cheung, Linda; Gratton, Michael Anne; Phillips, Grady; Song, Wenping; Liu, Shiguang; Cosgrove, Dominic

    2016-08-01

    Recent work demonstrates that Alport glomerular disease is mediated through a biomechanical strain-sensitive activation of mesangial actin dynamics. This occurs through a Rac1/CDC42 cross-talk mechanism that results in the invasion of the subcapillary spaces by mesangial filopodia. The filopodia deposit mesangial matrix proteins in the glomerular basement membrane, including laminin 211, which activates focal adhesion kinase in podocytes culminating in the up-regulation of proinflammatory cytokines and metalloproteinases. These events drive the progression of glomerulonephritis. Here we test whether endothelial cell-derived endothelin-1 is up-regulated in Alport glomeruli and further elevated by hypertension. Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan or under conditions of small, interfering RNA knockdown of endothelin A receptor mRNA. Treatment of Alport mice with sitaxentan results in delayed onset of proteinuria, normalized glomerular basement membrane morphology, inhibition of mesangial filopodial invasion of the glomerular capillaries, normalization of glomerular expression of metalloproteinases and proinflammatory cytokines, increased life span, and prevention of glomerulosclerosis and interstitial fibrosis. Thus endothelin A receptor activation on mesangial cells is a key event in initiation of Alport glomerular disease in this model.

  3. Initial clinical experience using the EchoNavigator®-system during structural heart disease interventions

    PubMed Central

    Balzer, Jan; Zeus, Tobias; Hellhammer, Katharina; Veulemans, Verena; Eschenhagen, Silke; Kehmeier, Eva; Meyer, Christian; Rassaf, Tienush; Kelm, Malte

    2015-01-01

    AIM: To present our initial clinical experience using this innovative software solution for guidance of percutaneous structural heart disease interventions. METHODS: Left atrial appendage, atrial septal defect and paravalvular leak closure, transaortic valve repair and MitraClip® procedures were performed in the catheter laboratory under fluoroscopic and echocardiographic guidance. The two-dimensional and three-dimensional images generated by the transesophageal echocardiography probe were interfaced with the fluoroscopic images in real-time using the EchoNavigator®-system. RESULTS: The application of the novel image fusion technology was safe and led to a better appreciation of multimodality imaging guidance due to improved visualization of the complex relationship between catheter devices and anatomical structures. CONCLUSION: The EchoNavigator®-system is a feasible and safe tool for guidance of interventional procedures in structural heart disease. This innovative technology may improve confidence of interventional cardiologists in targeting and positioning interventional devices in order to increase safety, accuracy, and efficacy of percutaneous interventions in the catheter laboratory. PMID:26413233

  4. Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

    PubMed Central

    Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

    2015-01-01

    Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

  5. Periodic fever in MVK deficiency: a patient initially diagnosed with incomplete Kawasaki disease.

    PubMed

    Thors, Valtyr S; Vastert, Sebastiaan J; Wulffraat, Nico; van Royen, Annet; Frenkel, Joost; de Sain-van der Velden, Monique; de Koning, Tom J

    2014-02-01

    Mevalonate kinase deficiency (MKD) is a rare autosomal recessive disorder causing 1 of 2 phenotypes, hyperimmunoglobulin D syndrome and mevalonic aciduria, presenting with recurrent fever episodes, often starting in infancy, and sometimes evoked by stress or vaccinations. This autoinflammatory disease is caused by mutations encoding the mevalonate kinase (MVK) gene and is classified in the group of periodic fever syndromes. There is often a considerable delay in the diagnosis among pediatric patients with recurrent episodes of fever. We present a case of an 8-week-old girl with fever of unknown origin and a marked systemic inflammatory response. After excluding infections, a tentative diagnosis of incomplete Kawasaki syndrome was made, based on the finding of dilated coronary arteries on cardiac ultrasound and fever, and she was treated accordingly. However, the episodes of fever recurred, and alternative diagnoses were considered, which eventually led to the finding of increased excretion of mevalonic acid in urine. The diagnosis of MKD was confirmed by mutation analysis of the MVK gene. This case shows that the initial presentation of MKD can be indistinguishable from incomplete Kawasaki syndrome. When fever recurs in Kawasaki syndrome, other (auto-)inflammatory diseases must be ruled out to avoid inappropriate diagnostic procedures, ineffective interventions, and treatment delay.

  6. Manganese-Enhanced MRI: An Exceptional Tool in Translational Neuroimaging

    PubMed Central

    Silva, Afonso C.; Bock, Nicholas A.

    2008-01-01

    The metal manganese is a potent magnetic resonance imaging (MRI) contrast agent that is essential in cell biology. Manganese-enhanced magnetic resonance imaging (MEMRI) is providing unique information in an ever-growing number of applications aimed at understanding the anatomy, the integration, and the function of neural circuits both in normal brain physiology as well as in translational models of brain disease. A major drawback to the use of manganese as a contrast agent, however, is its cellular toxicity. Therefore, paramount to the successful application of MEMRI is the ability to deliver Mn2+ to the site of interest using as low a dose as possible while preserving detectability by MRI. In the present work, the different approaches to MEMRI in translational neuroimaging are reviewed and challenges for future identified from a practical standpoint. PMID:18550591

  7. The current situation of meningococcal disease in Latin America and updated Global Meningococcal Initiative (GMI) recommendations.

    PubMed

    Sáfadi, Marco Aurélio P; O'Ryan, Miguel; Valenzuela Bravo, Maria Teresa; Brandileone, Maria Cristina C; Gorla, Maria Cecília O; de Lemos, Ana Paula S; Moreno, Gabriela; Vazquez, Julio A; López, Eduardo L; Taha, Muhamed-Kheir; Borrow, Ray

    2015-11-27

    The Global Meningococcal Initiative (GMI) was established in 2009 and comprises an international team of scientists, clinicians, and public health officials with expertise in meningococcal disease (MD). Its primary goal is to promote global prevention of MD through education, research, international cooperation, and developing recommendations that include decreasing the burden of severe disease. The group held its first roundtable meeting with experts from Latin American countries in 2011, and subsequently proposed several recommendations to reduce the regional burden of MD. A second roundtable meeting was convened with Latin American representatives in June 2013 to reassess MD epidemiology, vaccination strategies, and unmet needs in the region, as well as to update the earlier recommendations. Special emphasis was placed on the emergence and spread of serogroup W disease in Argentina and Chile, and the control measures put in place in Chile were a particular focus of discussions. The impact of routine meningococcal vaccination programs, notably in Brazil, was also evaluated. There have been considerable improvements in MD surveillance systems and diagnostic techniques in some countries (e.g., Brazil and Chile), but the lack of adequate infrastructure, trained personnel, and equipment/reagents remains a major barrier to progress in resource-poor countries. The Pan American Health Organization's Revolving Fund is likely to play an important role in improving access to meningococcal vaccines in Latin America. Additional innovative approaches are needed to redress the imbalance in expertise and resources between countries, and thereby improve the control of MD. In Latin America, the GMI recommends establishment of a detailed and comprehensive national/regional surveillance system, standardization of laboratory procedures, adoption of a uniform MD case definition, maintaining laboratory-based surveillance, replacement of polysaccharide vaccines with conjugate

  8. Human African trypanosomiasis with 7-year incubation period: clinical, laboratory and neuroimaging findings.

    PubMed

    Wengert, Oliver; Kopp, Marcel; Siebert, Eberhard; Stenzel, Werner; Hegasy, Guido; Suttorp, Norbert; Stich, August; Zoller, Thomas

    2014-06-01

    Human African trypanosomiasis (HAT), also referred to as "sleeping sickness", is caused by the parasite Trypanosoma brucei. Diagnosing imported HAT outside endemic areas is difficult and diagnosis is often delayed. We report a case of imported human African trypanosomiasis caused by Trypanosoma brucei gambiense with an unusually long incubation period of at least 7 years. A 33 year old male African patient, a former resident of Cameroon, presented with a 4-month history of progressive personality changes. A few weeks before presentation the patient had first been admitted to a psychiatric ward and received antidepressant treatment, until a lumbar puncture showed pleocytosis and then antibiotic treatment for suspected neuroborreliosis was initiated. The patient continued to deteriorate during antibiotic treatment and became increasingly lethargic. Under antiparasitic and anti-inflammatory treatment, the condition of the patient gradually improved over the following months and he recovered completely after 24 months of follow-up. This well-documented case illustrates typical difficulties in establishing the correct diagnosis outside endemic areas and provides an overview of typical clinical, neuropathological and neuroimaging findings in T. b. gambiense trypanosomiasis, guiding the clinician in establishing the correct diagnosis in this rare disease.

  9. Applications of Optical Neuroimaging in Usability Research

    PubMed Central

    Hill, Audrey P.; Bohil, Corey J.

    2016-01-01

    FEATURE AT A GLANCE In this article we review recent and potential applications of optical neuroimaging to human factors and usability research. We focus specifically on functional near-infrared spectroscopy (fNIRS) because of its cost-effectiveness and ease of implementation. Researchers have used fNIRS to assess a range of psychological phenomena relevant to human factors, such as cognitive workload, attention, motor activity, and more. It offers the opportunity to measure hemodynamic correlates of mental activity during task completion in human factors and usability studies. We also consider some limitations and future research directions. PMID:28286404

  10. Practical management of heterogeneous neuroimaging metadata by global neuroimaging data repositories.

    PubMed

    Neu, Scott C; Crawford, Karen L; Toga, Arthur W

    2012-01-01

    Rapidly evolving neuroimaging techniques are producing unprecedented quantities of digital data at the same time that many research studies are evolving into global, multi-disciplinary collaborations between geographically distributed scientists. While networked computers have made it almost trivial to transmit data across long distances, collecting and analyzing this data requires extensive metadata if the data is to be maximally shared. Though it is typically straightforward to encode text and numerical values into files and send content between different locations, it is often difficult to attach context and implicit assumptions to the content. As the number of and geographic separation between data contributors grows to national and global scales, the heterogeneity of the collected metadata increases and conformance to a single standardization becomes implausible. Neuroimaging data repositories must then not only accumulate data but must also consolidate disparate metadata into an integrated view. In this article, using specific examples from our experiences, we demonstrate how standardization alone cannot achieve full integration of neuroimaging data from multiple heterogeneous sources and why a fundamental change in the architecture of neuroimaging data repositories is needed instead.

  11. The Extensible Neuroimaging Archive Toolkit: an informatics platform for managing, exploring, and sharing neuroimaging data.

    PubMed

    Marcus, Daniel S; Olsen, Timothy R; Ramaratnam, Mohana; Buckner, Randy L

    2007-01-01

    The Extensible Neuroimaging Archive Toolkit (XNAT) is a software platform designed to facilitate common management and productivity tasks for neuroimaging and associated data. In particular, XNAT enables qualitycontrol procedures and provides secure access to and storage of data. XNAT follows a threetiered architecture that includes a data archive, user interface, and middleware engine. Data can be entered into the archive as XML or through data entry forms. Newly added data are stored in a virtual quarantine until an authorized user has validated it. XNAT subsequently maintains a history profile to track all changes made to the managed data. User access to the archive is provided by a secure web application. The web application provides a number of quality control and productivity features, including data entry forms, data-type-specific searches, searches that combine across data types, detailed reports, and listings of experimental data, upload/download tools, access to standard laboratory workflows, and administration and security tools. XNAT also includes an online image viewer that supports a number of common neuroimaging formats, including DICOM and Analyze. The viewer can be extended to support additional formats and to generate custom displays. By managing data with XNAT, laboratories are prepared to better maintain the long-term integrity of their data, to explore emergent relations across data types, and to share their data with the broader neuroimaging community.

  12. Integrative Bayesian Analysis of Neuroimaging-Genetic Data with Application to Cocaine Dependence

    PubMed Central

    Azadeh, Shabnam; Hobbs, Brian P.; Ma, Liangsuo; Nielsen, David A.; Moeller, F. Gerard; Baladandayuthapani, Veerabhadran

    2016-01-01

    Neuroimaging and genetic studies provide distinct and complementary information about the structural and biological aspects of a disease. Integrating the two sources of data facilitates the investigation of the links between genetic variability and brain mechanisms among different individuals for various medical disorders. This article presents a general statistical framework for integrative Bayesian analysis of neuroimaging-genetic (iBANG) data, which is motivated by a neuroimaging-genetic study in cocaine dependence. Statistical inference necessitated the integration of spatially dependent voxel-level measurements with various patient-level genetic and demographic characteristics under an appropriate probability model to account for the multiple inherent sources of variation. Our framework uses Bayesian model averaging to integrate genetic information into the analysis of voxel-wise neuroimaging data, accounting for spatial correlations in the voxels. Using multiplicity controls based on the false discovery rate, we delineate voxels associated with genetic and demographic features that may impact diffusion as measured by fractional anisotropy (FA) obtained from DTI images. We demonstrate the benefits of accounting for model uncertainties in both model fit and prediction. Our results suggest that cocaine consumption is associated with FA reduction in most white matter regions of interest in the brain. Additionally, gene polymorphisms associated with GABAergic, serotonergic and dopaminergic neurotransmitters and receptors were associated with FA. PMID:26484829

  13. 78 FR 56236 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the... Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry. Elaine L....

  14. [Gait disorders in Parkinson disease. Clinical description, analysis of posture, initiation of stabilized gait].

    PubMed

    Kemoun, G; Defebvre, L

    2001-03-10

    A WELL INFORMED DESCRIPTION: The parkinsonian posture is generally described as a stooped one. At the beginning of the disease, the gait troubles remain moderate; gradually the gait is composed of small steps without a wide base; the patient tends to run after his centre of gravity by accelerating the step (festination phenomenon). Difficulties occurs for starting up (delay of gait initiation), for about-turn or for clearing obstacles. Kinetic jammings and standing around (freezing) can last several seconds and be responsible for falls. POSTURAL INSTABILITY, A MAJOR SYMPTOM IN PARKINSON'S DISEASE: This symptom is little improved by therapies and is responsible for serious disability. Postural instability induces a disequilibrium and is partially due to a simultaneous antagonist muscles contraction and to the impossibility of modifying postural responses to changing support conditions. The passive viscoelastic properties of muscles and tendons constitute a first line of defence against the disequilibrium and contribute to postural stability in the case of medium disturbances. Automatic and voluntary postural responses which come into play in the case of major disturbances can also be impaired (delay or defect of the responses). GAIT INITIATION FAILURE ARE FREQUENT: They result from an increase of the postural phase and a decrease of the propulsion forces, depending on a deficit of the postural anticipation mechanisms and also the sequential organization and the integration of two different motor programs, postural and locomotor. They can be controlled partially with sensory stimuli, notably visual inputs. DATA CONCERNING STABILIZED WALKING AND ITS PATHOPHYSIOLOGY REMAINS TO BE CLARIFIED: Spatial and temporal parameters are impaired: speed, step length and swing phase are reduced, while cadence increases to compensate these troubles. These modifications are the consequence of an incapacity to produce internal marks to generate regular steps. When the parkinsonian

  15. About the J-GRID (Japan Initiative for Global Research Network on Infectious Diseases)

    PubMed Central

    2014-01-01

    Since infectious diseases heed no national borders, international research collaboration across borders must be enhanced. The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan launched the J-GRID program in the fiscal year (FY) 2005, which consists of the two elements; (1) the construction of collaboration centers in Asian and African countries on a reciprocal basis between a Japanese university/institution and an overseas partner university/institution and (2) the networking of those collaboration centers and setting up its headquarters at RIKEN. J-GRID initiated with 5 collaboration centers in 3 Asian countries has expanded to include 13 centers in 8 countries (6 in Asia and 2 in Africa). The aims of J-GRID include conducting high quality research on infectious diseases of regional and global importance, advancing relevant technologies and developing human resources in the field. In this way, J-GRID is expected to contribute to the public health of the host countries, Japan and the rest of the world. After the completion of the first start-up phase, Term I (2005–2009), J-GRID has stepped up its activity for the second step-up phase, Term II (2010–2014). While the first term was just like an incubation period, the second term should be the exponential growth phase, maximizing its research activities. Indeed, J-GRID is now generating remarkable research outcomes with an increasing number of publications. The mid-term evaluation made by the MEXT in FY2012 commended J-GRID as an ideal model to demonstrate Japan’s leadership, in science and technology, and strongly recommended its extension in years to come after Term II terminates in FY 2014. PMID:25425950

  16. Risk Factors in the Initial Presentation of Specific Cardiovascular Disease Syndromes

    ClinicalTrials.gov

    2013-03-03

    Heart Diseases; Cardiovascular Diseases; Acute Myocardial Infarction; Unstable Angina; Chronic Stable Angina; Ischemic Stroke; Cerebrovascular Accident; Subarachnoid Hemorrhage; Transient Ischemic Attack; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Sudden Coronary Death; Ventricular Arrhythmia; Sudden Death; Cardiac Arrest; Heart Failure

  17. Reproducibility of neuroimaging analyses across operating systems.

    PubMed

    Glatard, Tristan; Lewis, Lindsay B; Ferreira da Silva, Rafael; Adalat, Reza; Beck, Natacha; Lepage, Claude; Rioux, Pierre; Rousseau, Marc-Etienne; Sherif, Tarek; Deelman, Ewa; Khalili-Mahani, Najmeh; Evans, Alan C

    2015-01-01

    Neuroimaging pipelines are known to generate different results depending on the computing platform where they are compiled and executed. We quantify these differences for brain tissue classification, fMRI analysis, and cortical thickness (CT) extraction, using three of the main neuroimaging packages (FSL, Freesurfer and CIVET) and different versions of GNU/Linux. We also identify some causes of these differences using library and system call interception. We find that these packages use mathematical functions based on single-precision floating-point arithmetic whose implementations in operating systems continue to evolve. While these differences have little or no impact on simple analysis pipelines such as brain extraction and cortical tissue classification, their accumulation creates important differences in longer pipelines such as subcortical tissue classification, fMRI analysis, and cortical thickness extraction. With FSL, most Dice coefficients between subcortical classifications obtained on different operating systems remain above 0.9, but values as low as 0.59 are observed. Independent component analyses (ICA) of fMRI data differ between operating systems in one third of the tested subjects, due to differences in motion correction. With Freesurfer and CIVET, in some brain regions we find an effect of build or operating system on cortical thickness. A first step to correct these reproducibility issues would be to use more precise representations of floating-point numbers in the critical sections of the pipelines. The numerical stability of pipelines should also be reviewed.

  18. Auditory verbal hallucinations: neuroimaging and treatment.

    PubMed

    Bohlken, M M; Hugdahl, K; Sommer, I E C

    2017-01-01

    Auditory verbal hallucinations (AVH) are a frequently occurring phenomenon in the general population and are considered a psychotic symptom when presented in the context of a psychiatric disorder. Neuroimaging literature has shown that AVH are subserved by a variety of alterations in brain structure and function, which primarily concentrate around brain regions associated with the processing of auditory verbal stimuli and with executive control functions. However, the direction of association between AVH and brain function remains equivocal in certain research areas and needs to be carefully reviewed and interpreted. When AVH have significant impact on daily functioning, several efficacious treatments can be attempted such as antipsychotic medication, brain stimulation and cognitive-behavioural therapy. Interestingly, the neural correlates of these treatments largely overlap with brain regions involved in AVH. This suggests that the efficacy of treatment corresponds to a normalization of AVH-related brain activity. In this selected review, we give a compact yet comprehensive overview of the structural and functional neuroimaging literature on AVH, with a special focus on the neural correlates of efficacious treatment.

  19. Initial trial of argon ion laser endarterectomy for peripheral vascular disease

    SciTech Connect

    Eugene, J.; Ott, R.A.; Baribeau, Y.; McColgan, S.J.; Berns, M.W.; Mason, G.R. )

    1990-08-01

    In the initial of open laser endarterectomy, 16 patients underwent 18 reconstructions for claudication (13 patients), rest pain (3 patients), and gangrene (2 patients). The mean (+/- SD) preoperative ankle arm index was 0.53 +/- 0.18. The laser endarterectomies were aorto-bi-iliac (1 patient), iliac (1 patient), superficial femoral (7 patients), profunda femoral (7 patients), and popliteal-posterior tibial (2 patients). All operations included surgical exposure, vascular control, administration of heparin, and an arteriotomy. Atheromas were dissected from arteries with argon ion laser radiation (power, 1.0 W). End points were welded with laser light. Arteries were closed primarily. The laser endarterectomies were 6 to 60 cm long and required 168 J to 2447.5 J. All patients had symptomatic relief, with a postoperative ankle arm index of 0.97 +/- 0.10. There were no arterial perforations from laser radiation. Surgical complications included early thrombosis requiring thrombectomy (3 patients) and hematoma requiring evacuation (1 patient). The laser endarterectomies have an 88% patency at 1 year. Open endarterectomy can be performed with laser radiation. A larger clinical trial is necessary to define the indications for laser endarterectomy in peripheral vascular disease.

  20. Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature

    PubMed Central

    Walitt, Brian; Čeko, Marta; Gracely, John L.; Gracely, Richard H.

    2016-01-01

    Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging “signature” cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of “central sensitivity syndromes” is based more soundly on clinical and epidemiological evidence. A coherent picture of a “central sensitization” mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence. PMID:26717948

  1. 78 FR 19490 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

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  15. Single subject prediction of brain disorders in neuroimaging: Promises and pitfalls.

    PubMed

    Arbabshirani, Mohammad R; Plis, Sergey; Sui, Jing; Calhoun, Vince D

    2017-01-15

    Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need

  16. Fever of unknown origin and leukemoid reaction as initial presentation of adult-onset Still's disease.

    PubMed

    Pardo-Cabello, Alfredo José; Manzano-Gamero, Victoria; Javier-Martínez, Rosario

    2014-01-01

    Adult Still's Disease has been reported as cause of Fever of Unknown Origin. Leukocytosis has been described as a common haematological abnormality in Adult Still's Disease. In some rare cases, leukemoid reaction has been reported associated to Still's Disease. We report the case of Adult Still's Disease presenting as Fever of Unknown Origin and leukemoid reaction in a patient with Down Syndrome. The patient needed high dosage of corticosteroids to control the disease and haematological findings.

  17. 77 FR 39498 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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  18. 78 FR 6329 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... Treatments and Services Provided to People with ] Duchenne Muscular Dystrophy (DMD), FOA DD13-002, initial... with Duchenne Muscular Dystrophy (DMD), FOA DD13-002, initial review.'' Contact Person for...

  19. Turner Syndrome: Neuroimaging Findings--Structural and Functional

    ERIC Educational Resources Information Center

    Mullaney, Ronan; Murphy, Declan

    2009-01-01

    Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including…

  20. Cognitive Neuroimaging: Cognitive Science out of the Armchair

    ERIC Educational Resources Information Center

    de Zubicaray, Greig I.

    2006-01-01

    Cognitive scientists were not quick to embrace the functional neuroimaging technologies that emerged during the late 20th century. In this new century, cognitive scientists continue to question, not unreasonably, the relevance of functional neuroimaging investigations that fail to address questions of interest to cognitive science. However, some…

  1. Childhood-Onset Schizophrenia: Insights from Neuroimaging Studies

    ERIC Educational Resources Information Center

    Gogtay, Nitin; Rapoport, Judith L.

    2008-01-01

    The use of longitudinal neuroimaging to study the developmental perspectives of brain pathology in children with childhood-onset schizophrenia (COS) is described. Structural neuroimaging is capable of providing evidence of neurobiological specificity of COS to distinguish it from other brain abnormalities seen in neuropsychiatric illnesses like…

  2. Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?

    PubMed Central

    Portugal, Liana C. L.; Rosa, Maria João; Rao, Anil; Bebko, Genna; Bertocci, Michele A.; Hinze, Amanda K.; Bonar, Lisa; Almeida, Jorge R. C.; Perlman, Susan B.; Versace, Amelia; Schirda, Claudiu; Travis, Michael; Gill, Mary Kay; Demeter, Christine; Diwadkar, Vaibhav A.; Ciuffetelli, Gary; Rodriguez, Eric; Forbes, Erika E.; Sunshine, Jeffrey L.; Holland, Scott K.; Kowatch, Robert A.; Birmaher, Boris; Axelson, David; Horwitz, Sarah M.; Arnold, Eugene L.; Fristad, Mary A.; Youngstrom, Eric A.; Findling, Robert L.; Pereira, Mirtes; Oliveira, Leticia; Phillips, Mary L.; Mourao-Miranda, Janaina

    2016-01-01

    Introduction High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points. Methods A sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson’s correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels. Results Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern

  3. Neuromarketing: the hope and hype of neuroimaging in business

    PubMed Central

    Ariely, Dan; Berns, Gregory S.

    2010-01-01

    The application of neuroimaging methods to product marketing — neuromarketing — has recently gained considerable popularity. We propose that there are two main reasons for this trend. First, the possibility that neuroimaging will become cheaper and faster than other marketing methods; and second, the hope that neuroimaging will provide marketers with information that is not obtainable through conventional marketing methods. Although neuroimaging is unlikely to be cheaper than other tools in the near future, there is growing evidence that it may provide hidden information about the consumer experience. The most promising application of neuroimaging methods to marketing may come before a product is even released — when it is just an idea being developed. PMID:20197790

  4. A Review on the Bioinformatics Tools for Neuroimaging

    PubMed Central

    MAN, Mei Yen; ONG, Mei Sin; Mohamad, Mohd Saberi; DERIS, Safaai; SULONG, Ghazali; YUNUS, Jasmy; CHE HARUN, Fauzan Khairi

    2015-01-01

    Neuroimaging is a new technique used to create images of the structure and function of the nervous system in the human brain. Currently, it is crucial in scientific fields. Neuroimaging data are becoming of more interest among the circle of neuroimaging experts. Therefore, it is necessary to develop a large amount of neuroimaging tools. This paper gives an overview of the tools that have been used to image the structure and function of the nervous system. This information can help developers, experts, and users gain insight and a better understanding of the neuroimaging tools available, enabling better decision making in choosing tools of particular research interest. Sources, links, and descriptions of the application of each tool are provided in this paper as well. Lastly, this paper presents the language implemented, system requirements, strengths, and weaknesses of the tools that have been widely used to image the structure and function of the nervous system. PMID:27006633

  5. Pituitary gland in psychiatric disorders: a review of neuroimaging findings.

    PubMed

    Atmaca, Murad

    2014-08-01

    In this paper, it was reviewed neuroimaging results of the pituitary gland in psychiatric disorders, particularly schizophrenia, mood disorders, anxiety disorders, and somatoform disorders. The author made internet search in detail by using PubMed database including the period between 1980 and 2012 October. It was included in the articles in English, Turkish and French languages on pituitary gland in psychiatric disorders through structural or functional neuroimaging results. After searching mentioned in the Methods section in detail, investigations were obtained on pituitary gland neuroimaging in a variety of psychiatric disorders. There have been so limited investigations on pituitary neuroimaging in psychiatric disorders including major psychiatric illnesses like schizophrenia and mood disorders. Current findings are so far from the generalizability of the results. For this reason, it is required to perform much more neuroimaging studies of pituitary gland in all psychiatric disorders to reach the diagnostic importance of measuring it.

  6. Cardiovascular Health and Incident Cardiovascular Disease and Cancer: The Women's Health Initiative

    PubMed Central

    Foraker, Randi E.; Abdel-Rasoul, Mahmoud; Kuller, Lewis H.; Jackson, Rebecca D.; Van Horn, Linda; Seguin, Rebecca A.; Safford, Monika M.; Wallace, Robert B.; Kucharska-Newton, Anna M.; Robinson, Jennifer G.; Martin, Lisa W.; Agha, Golareh; Hou, Lifang; Allen, Norrina B.; Tindle, Hilary A.

    2015-01-01

    Introduction The American Heart Association's “Simple 7” offers a practical public health conceptualization of cardiovascular health (CVH). CVH predicts incident cardiovascular disease (CVD) in younger populations, but has not been studied in a large, diverse population of aging postmenopausal women. The extent to which CVH predicts cancer in postmenopausal women is unknown. Methods Multivariable Cox regression estimated hazard ratios and 95% CIs for the association between CVH and incident CVD, any cancer, and cancer subtypes (lung, colorectal, and breast) among 161,809 Women's Health Initiative observational study and clinical trial participants followed from 1993 through 2010. Data were analyzed in 2013. CVH score was characterized as the number (0 [worst] to 7 [best]) of the American Heart Association's ideal CVH behaviors and factors at baseline: smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting glucose. Results Median follow-up was approximately 13 years. Fewer minorities and less educated women achieved ideal CVH, a common benchmark. In adjusted models, compared with women with the highest (best) CVH scores, those with the lowest (worst) CVH scores had nearly seven times the hazard of incident CVD (6.83, 95% CI=5.83, 8.00), and 52% greater risk of incident cancer (1.52, 95% CI=1.35, 1.72). Ideal CVH was most strongly inversely associated with lung cancer, then colorectal cancer, and then breast cancer. Conclusions Lower ideal CVH is more common among minority and less educated postmenopausal women, and predicts increased risk of CVD and cancer in this population, emphasizing the importance of prevention efforts among vulnerable older adults. PMID:26456876

  7. Kawasaki Disease with Fever and Cervical Lymphadenopathy as the Sole Initial Presentation

    PubMed Central

    Jun, Woo Young; Ann, Yu Kyung; Kim, Ja Yeong; Kim, Soo-Jin; Yang, Hyun Suk; Bae, Sun Hwan; Chung, Sochung; Kim, Kyo Sun

    2017-01-01

    Background and Objectives Some patients with Kawasaki disease (KD) present with fever and cervical lymphadenopathy alone. The purpose of this study was to characterize the clinical features of these unusual KD patients and determine whether this is a severe form of KD associated with increased risks of intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). Subjects and Methods A total of 146 children with KD were reviewed retrospectively, and classified into two groups according to initial clinical features. Those presenting with only fever and cervical lymphadenopathy (LKD) were classified as LKD patients. Other-KD patients included all except the LKD patients. Results Among 146 KD patients, 13 (8.9%) were classified as LKD patients. The LKD patients were significantly older and admitted earlier. The duration between fever onset and KD diagnosis was significantly longer in the LKD patients (5.9 days vs. 4.9 days, p=0.023). The frequency of IVIG resistance was not different between the two groups., In the LKD patients, the incidence of CALs was significantly higher in the acute phase, and without significant difference in the convalescent phase. The percentage of neutrophils and C-reactive protein, albumin, and total bilirubin levels were significantly higher in LKD patients. Conclusion Even though LKD patients were older, admitted earlier, and had higher inflammatory marker levels, they did not have a greater risk of CALs or IVIG resistance. However, echocardiography may be helpful in the acute stage if patients have only fever and cervical lymphadenopathy and are unresponsive to empirical antibiotics. PMID:28154598

  8. Systems Biology, Neuroimaging, Neuropsychology, Neuroconnectivity and Traumatic Brain Injury

    PubMed Central

    Bigler, Erin D.

    2016-01-01

    The patient who sustains a traumatic brain injury (TBI) typically undergoes neuroimaging studies, usually in the form of computed tomography (CT) and magnetic resonance imaging (MRI). In most cases the neuroimaging findings are clinically assessed with descriptive statements that provide qualitative information about the presence/absence of visually identifiable abnormalities; though little if any of the potential information in a scan is analyzed in any quantitative manner, except in research settings. Fortunately, major advances have been made, especially during the last decade, in regards to image quantification techniques, especially those that involve automated image analysis methods. This review argues that a systems biology approach to understanding quantitative neuroimaging findings in TBI provides an appropriate framework for better utilizing the information derived from quantitative neuroimaging and its relation with neuropsychological outcome. Different image analysis methods are reviewed in an attempt to integrate quantitative neuroimaging methods with neuropsychological outcome measures and to illustrate how different neuroimaging techniques tap different aspects of TBI-related neuropathology. Likewise, how different neuropathologies may relate to neuropsychological outcome is explored by examining how damage influences brain connectivity and neural networks. Emphasis is placed on the dynamic changes that occur following TBI and how best to capture those pathologies via different neuroimaging methods. However, traditional clinical neuropsychological techniques are not well suited for interpretation based on contemporary and advanced neuroimaging methods and network analyses. Significant improvements need to be made in the cognitive and behavioral assessment of the brain injured individual to better interface with advances in neuroimaging-based network analyses. By viewing both neuroimaging and neuropsychological processes within a systems biology

  9. How Shakespeare tempests the brain: neuroimaging insights.

    PubMed

    Keidel, James L; Davis, Philip M; Gonzalez-Diaz, Victorina; Martin, Clara D; Thierry, Guillaume

    2013-04-01

    Shakespeare made extensive use of the functional shift (FS), a rhetorical device involving a change in the grammatical status of words, e.g., using nouns as verbs. Previous work using event-related brain potentials showed how FS triggers a surprise effect inviting mental re-evaluation, seemingly independent of semantic processing. Here, we used functional magnetic resonance imaging to investigate brain activation in participants making judgements on the semantic relationship between sentences -some containing a Shakespearean FS- and subsequently presented words. Behavioural performance in the semantic decision task was high and unaffected by sentence type. However, neuroimaging results showed that sentences featuring FS elicited significant activation beyond regions classically activated by typical language tasks, including the left caudate nucleus, the right inferior frontal gyrus and the right inferior temporal gyrus. These findings show how Shakespeare's grammatical exploration forces the listener to take a more active role in integrating the meaning of what is said.

  10. Neuroimaging for drug addiction and related behaviors

    SciTech Connect

    Parvaz M. A.; Parvaz, M.A.; Alia-Klein, N.; Woicik,P.A.; Volkow, N.D.; Goldstein, R.Z.

    2011-10-01

    In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors.

  11. Neuroimaging for drug addiction and related behaviors

    PubMed Central

    Parvaz, Muhammad A.; Alia-Klein, Nelly; Woicik, Patricia A.; Volkow, Nora D.; Goldstein, Rita Z.

    2012-01-01

    In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors. PMID:22117165

  12. An Overview of Multimodal Neuroimaging Using Nanoprobes

    PubMed Central

    Sridhar, Sriram; Mishra, Sachin; Gulyás, Miklós; Padmanabhan, Parasuraman; Gulyás, Balázs

    2017-01-01

    Nanomaterials have gained tremendous significance as contrast agents for both anatomical and functional preclinical bio-imaging. Contrary to conventional medical practices, molecular imaging plays an important role in exploring the affected cells, thus providing precision medical solutions. It has been observed that incorporating nanoprobes improves the overall efficacy of the diagnosis and treatment processes. These nano-agents and tracers are therefore often incorporated into preclinical therapeutic and diagnostic applications. Multimodal imaging approaches are well equipped with nanoprobes to explore neurological disorders, as they can display more than one type of characteristic in molecular imaging. Multimodal imaging systems are explored by researchers as they can provide both anatomical and functional details of tumors and affected tissues. In this review, we present the state-of-the-art research concerning multimodal imaging systems and nanoprobes for neuroimaging applications. PMID:28157157

  13. The teen brain: insights from neuroimaging.

    PubMed

    Giedd, Jay N

    2008-04-01

    Few parents of a teenager are surprised to hear that the brain of a 16-year-old is different from the brain of an 8-year-old. Yet to pin down these differences in a rigorous scientific way has been elusive. Magnetic resonance imaging, with the capacity to provide exquisitely accurate quantifications of brain anatomy and physiology without the use of ionizing radiation, has launched a new era of adolescent neuroscience. Longitudinal studies of subjects from ages 3-30 years demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, extending well into young adulthood. Although overinterpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the implications of these brain changes on cognition, emotion, and behavior.

  14. The experience of art: insights from neuroimaging.

    PubMed

    Nadal, Marcos

    2013-01-01

    The experience of art is a complex one. It emerges from the interaction of multiple cognitive and affective processes. Neuropsychological and neuroimaging studies are revealing the broadly distributed network of brain regions upon which it relies. This network can be divided into three functional components: (i) prefrontal, parietal, and temporal cortical regions support evaluative judgment, attentional processing, and memory retrieval; (ii) the reward circuit, including cortical, subcortical regions, and some of its regulators, is involved in the generation of pleasurable feelings and emotions, and the valuation and anticipation of reward; and (iii) attentional modulation of activity in low-, mid-, and high-level cortical sensory regions enhances the perceptual processing of certain features, relations, locations, or objects. Understanding how these regions act in concert to produce unique and moving art experiences and determining the impact of personal and cultural meaning and context on this network the biological foundation of the experience of art--remain future challenges.

  15. The Northwestern University Neuroimaging Data Archive (NUNDA)

    PubMed Central

    Alpert, Kathryn; Kogan, Alexandr; Parrish, Todd; Marcus, Daniel; Wang, Lei

    2015-01-01

    The Northwestern University Neuroimaging Data Archive (NUNDA), an XNAT-powered data archiving system, aims to facilitate secure data storage; centralized data management; automated, standardized data processing; and simple, intuitive data sharing. NUNDA is a federated data archive, wherein individual project owners regulate access to their data. NUNDA supports multiple methods of data import, enabling data collection in a central repository. Data in NUNDA are available by project to any authorized user, allowing coordinated data management and review across sites. With NUNDA pipelines, users capitalize on existing procedures or standardize custom routines for consistent, automated data processing. NUNDA can be integrated with other research databases to simplify data exploration and discovery. And data on NUNDA can be confidently shared for secure collaboration. PMID:26032888

  16. [Functional neuroimaging of auditory hallucinations in schizophrenia].

    PubMed

    Font, M; Parellada, E; Fernández-Egea, E; Bernardo, M; Lomeña, F

    2003-01-01

    The neurobiological bases underlying the generation of auditory hallucinations, a distressing and paradigmatic symptom of schizophrenia, are still unknown in spite of in-depth phenomenological descriptions. This work aims to make a critical review of the latest published literature in recent years, focusing on functional neuroimaging studies (PET, SPECT, fMRI) of auditory hallucinations. Thus, the studies are classified according to whether they are sensory activation, trait and state. The two main hypotheses proposed to explain the phenomenon, external speech vs. subvocal or inner speech, are also explained. Finally, the latest unitary theory as well as the limitations the studies published are commented on. The need to continue investigating in this field, that is still underdeveloped, is posed in order to understand better the etiopathogenesis of auditory hallucinations in schizophrenia.

  17. A Supranuclear Disorder of Ocular Motility as a Rare Initial Presentation of Motor Neurone Disease.

    PubMed

    Yu-Wai-Man, C; Petheram, K; Davidson, A W; Williams, T; Griffiths, P G

    2011-01-01

    A case is described of motor neurone disease presenting with an ocular motor disorder characterised by saccadic intrusions, impaired horizontal and vertical saccades, and apraxia of eyelid opening. The occurrence of eye movement abnormalities in motor neurone disease is discussed.

  18. Social Deprivation and Initial Presentation of 12 Cardiovascular Diseases: a CALIBER Study

    ClinicalTrials.gov

    2013-09-03

    Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Corronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

  19. Federal Initiative: Tick-Borne Disease Integrated Pest Management White Paper

    EPA Pesticide Factsheets

    The numbers of human cases of Lyme disease and other tick-borne diseases (TBDs) reported each year to CDC have been increasing steadily in the United States (US), currently totaling tens of thousands of diagnosed human cases annually.

  20. African goat improvement project: A feed the future initiative harnessing geneticdiversity for conservation, disease resistance, and improved productivity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    AFRICAN GOAT IMPROVEMENT PROJECT: A FEED THE FUTURE INITIATIVE HARNESSING GENETIC DIVERSITY FOR CONSERVATION, DISEASE RESISTANCE, AND IMPROVED PRODUCTIVITY Food production systems in Africa depend heavily on the use of locally adapted animals. These animals are of agricultural, cultural, and econom...

  1. Dietary Patterns Predict Subsequent Coronary Heart Disease Risk In Postmenopausal Women : The Women’s Health Initiative Observational Cohort Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Evidence suggests that dietary patterns predispose to the development of coronary heart disease (CHD). The relationship between dietary patterns and CHD risk was assessed in postmenopausal women participating in the Women’s Health Initiative Observational Study (WHI-OS). Methods: Case-co...

  2. Neuroimaging of child abuse: a critical review

    PubMed Central

    Hart, Heledd; Rubia, Katya

    2012-01-01

    Childhood maltreatment is a stressor that can lead to the development of behavior problems and affect brain structure and function. This review summarizes the current evidence for the effects of childhood maltreatment on behavior, cognition and the brain in adults and children. Neuropsychological studies suggest an association between child abuse and deficits in IQ, memory, working memory, attention, response inhibition and emotion discrimination. Structural neuroimaging studies provide evidence for deficits in brain volume, gray and white matter of several regions, most prominently the dorsolateral and ventromedial prefrontal cortex but also hippocampus, amygdala, and corpus callosum (CC). Diffusion tensor imaging (DTI) studies show evidence for deficits in structural interregional connectivity between these areas, suggesting neural network abnormalities. Functional imaging studies support this evidence by reporting atypical activation in the same brain regions during response inhibition, working memory, and emotion processing. There are, however, several limitations of the abuse research literature which are discussed, most prominently the lack of control for co-morbid psychiatric disorders, which make it difficult to disentangle which of the above effects are due to maltreatment, the associated psychiatric conditions or a combination or interaction between both. Overall, the better controlled studies that show a direct correlation between childhood abuse and brain measures suggest that the most prominent deficits associated with early childhood abuse are in the function and structure of lateral and ventromedial fronto-limbic brain areas and networks that mediate behavioral and affect control. Future, large scale multimodal neuroimaging studies in medication-naïve subjects, however, are needed that control for psychiatric co-morbidities in order to elucidate the structural and functional brain sequelae that are associated with early environmental adversity

  3. 77 FR 29351 - Disease, Disability, and Injury Prevention and Control; Special Interest Projects (SIPs): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-17

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Adults to Inform Future Public Health Policy Efforts to Prevent Skin Cancer, SIP12-054, Pilot Study to... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date 11:00 a.m.-5:30...

  4. Multi-source feature learning for joint analysis of incomplete multiple heterogeneous neuroimaging data.

    PubMed

    Yuan, Lei; Wang, Yalin; Thompson, Paul M; Narayan, Vaibhav A; Ye, Jieping

    2012-07-02

    Analysis of incomplete data is a big challenge when integrating large-scale brain imaging datasets from different imaging modalities. In the Alzheimer's Disease Neuroimaging Initiative (ADNI), for example, over half of the subjects lack cerebrospinal fluid (CSF) measurements; an independent half of the subjects do not have fluorodeoxyglucose positron emission tomography (FDG-PET) scans; many lack proteomics measurements. Traditionally, subjects with missing measures are discarded, resulting in a severe loss of available information. In this paper, we address this problem by proposing an incomplete Multi-Source Feature (iMSF) learning method where all the samples (with at least one available data source) can be used. To illustrate the proposed approach, we classify patients from the ADNI study into groups with Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal controls, based on the multi-modality data. At baseline, ADNI's 780 participants (172AD, 397 MCI, 211 NC), have at least one of four data types: magnetic resonance imaging (MRI), FDG-PET, CSF and proteomics. These data are used to test our algorithm. Depending on the problem being solved, we divide our samples according to the availability of data sources, and we learn shared sets of features with state-of-the-art sparse learning methods. To build a practical and robust system, we construct a classifier ensemble by combining our method with four other methods for missing value estimation. Comprehensive experiments with various parameters show that our proposed iMSF method and the ensemble model yield stable and promising results.

  5. Multi-Source Learning for Joint Analysis of Incomplete Multi-Modality Neuroimaging Data.

    PubMed

    Yuan, Lei; Wang, Yalin; Thompson, Paul M; Narayan, Vaibhav A; Ye, Jieping

    2012-01-01

    Incomplete data present serious problems when integrating largescale brain imaging data sets from different imaging modalities. In the Alzheimer's Disease Neuroimaging Initiative (ADNI), for example, over half of the subjects lack cerebrospinal fluid (CSF) measurements; an independent half of the subjects do not have fluorodeoxyglucose positron emission tomography (FDG-PET) scans; many lack proteomics measurements. Traditionally, subjects with missing measures are discarded, resulting in a severe loss of available information. We address this problem by proposing two novel learning methods where all the samples (with at least one available data source) can be used. In the first method, we divide our samples according to the availability of data sources, and we learn shared sets of features with state-of-the-art sparse learning methods. Our second method learns a base classifier for each data source independently, based on which we represent each source using a single column of prediction scores; we then estimate the missing prediction scores, which, combined with the existing prediction scores, are used to build a multi-source fusion model. To illustrate the proposed approaches, we classify patients from the ADNI study into groups with Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal controls, based on the multi-modality data. At baseline, ADNI's 780 participants (172 AD, 397 MCI, 211 Normal), have at least one of four data types: magnetic resonance imaging (MRI), FDG-PET, CSF and proteomics. These data are used to test our algorithms. Comprehensive experiments show that our proposed methods yield stable and promising results.

  6. 77 FR 30292 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... Barriers to Receiving Breast and Cervical Cancer Screening Among Muslim Women Living in the United States... initial review, discussion, and evaluation of ``Identifying Barriers to Receiving Breast and...

  7. 77 FR 25180 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... Research on Moderate Acute Malnutrition in Humanitarian Emergencies, Funding Opportunity Announcement (FOA... Malnutrition in Humanitarian Emergencies, FOA GH12-006, initial review.'' Contact Person for More...

  8. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... Expansion and Reproductive Health Care for Women, FOA DP 13-002, initial review. In accordance with Section... to ``Medicaid Expansion and Reproductive Health Care for Women, FOA DP 13-002, initial review... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH...

  9. 77 FR 39497 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... Project (SIP): Evaluation of School Salad Bars as a Public Health Intervention to Increase Fruit and Vegetable Intake in Middle and High School Students, SIP12-063, Panel F, initial review. In accordance with... and Vegetable Intake in Middle and High School Students, SIP12-063, Panel F, initial review.''...

  10. Structural neuroimaging in preclinical dementia: From microstructural deficits and grey matter atrophy to macroscale connectomic changes.

    PubMed

    Mak, Elijah; Gabel, Silvy; Mirette, Habib; Su, Li; Williams, Guy B; Waldman, Adam; Wells, Katie; Ritchie, Karen; Ritchie, Craig; O'Brien, John

    2017-05-01

    The last decade has witnessed a proliferation of neuroimaging studies characterising brain changes associated with Alzheimer's disease (AD), where both widespread atrophy and 'signature' brain regions have been implicated. In parallel, a prolonged latency period has been established in AD, with abnormal cerebral changes beginning many years before symptom onset. This raises the possibility of early therapeutic intervention, even before symptoms, when treatments could have the greatest effect on disease-course modification. Two important prerequisites of this endeavour are (1) accurate characterisation or risk stratification and (2) monitoring of progression using neuroimaging outcomes as a surrogate biomarker in those without symptoms but who will develop AD, here referred to as preclinical AD. Structural neuroimaging modalities have been used to identify brain changes related to risk factors for AD, such as familial genetic mutations, risk genes (for example apolipoprotein epsilon-4 allele), and/or family history. In this review, we summarise structural imaging findings in preclinical AD. Overall, the literature suggests early vulnerability in characteristic regions, such as the medial temporal lobe structures and the precuneus, as well as white matter tracts in the fornix, cingulum and corpus callosum. We conclude that while structural markers are promising, more research and validation studies are needed before future secondary prevention trials can adopt structural imaging biomarkers as either stratification or surrogate biomarkers.

  11. Spinal Cord Lesions in Congenital Toxoplasmosis Demonstrated with Neuroimaging, Including Their Successful Treatment in an Adult

    PubMed Central

    Burrowes, Delilah; Boyer, Kenneth; Swisher, Charles N.; Noble, A. Gwendolyn; Sautter, Mari; Heydemann, Peter; Rabiah, Peter; Lee, Daniel; McLeod, Rima

    2012-01-01

    Neuroimaging studies for persons in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) with symptoms and signs referable to the spinal cord were reviewed. Three infants had symptomatic spinal cord lesions, another infant a Chiari malformation, and another infant a symptomatic peri-spinal cord lipoma. One patient had an unusual history of prolonged spinal cord symptoms presenting in middle age. Neuroimaging was used to establish her diagnosis and response to treatment. This 43 year-old woman with congenital toxoplasmosis developed progressive leg spasticity, weakness, numbness, difficulty walking, and decreased visual acuity and color vision without documented re-activation of her chorioretinal disease. At 52 years of age, spinal cord lesions in locations correlating with her symptoms and optic atrophy were diagnosed with 3 Tesla MRI scan. Treatment with pyrimethamine and sulfadiazine decreased her neurologic symptoms, improved her neurologic examination, and resolved her enhancing spinal cord lesions seen on MRI. PMID:23487348

  12. Understanding the Role of Autoimmune Disorders on the Initial Presentation of Cardiovascular Disease

    ClinicalTrials.gov

    2015-04-20

    Myocardial Infarction; Ischemic Stroke; Stroke; Subarachnoid Haemorrhage; Venous Thrombosis; Transient Ischemic Attack; Stable Angina Pectoris; Unstable Angina; Heart Failure; Peripheral Arterial Disease; Abdominal Aortic Aneurysm

  13. [Management of patients with end-stage renal disease prior to initiation of renal replacement therapy in 2013 in France].

    PubMed

    Tuppin, Philippe; Cuerq, Anne; Torre, Sylvie; Couchoud, Cécile; Fagot-Campagna, Anne

    2017-04-01

    This study evaluated the management of patients with end-stage renal disease prior to initiation of renal replacement therapy. Among the 51 million national health insurance general scheme beneficiaries (77% of the population), persons 18 years and older, starting dialysis or undergoing preemptive renal transplantation in 2013, were included in this study. Data were derived from the French national health insurance system (SNIIRAM). In this population of 6674 patients (median age: 68 years), 88% initiated renal replacement therapy by haemodialysis, 8% by peritoneal dialysis, and 4% by renal transplantation. During the year preceding initiation of dialysis, 76% of patients had been hospitalised with at least one diagnostic code for renal disease in 83% of cases, 16% had not received any reimbursements for serum creatinine assay and 32% had not seen a nephrologist; 87% were taking at least one antihypertensive drug (60% were taking at least a renin-angiotensin system inhibitor) and 30% were taking a combination of 4 or more classes of antihypertensive drugs. For patients initiating haemodialysis in a haemodialysis centre, 39% had undergone a procedure related to arteriovenous fistula and 10% had been admitted to an intensive care unit. This study, based on the available reimbursement data, shows that, despite frequent use of the health care system by this population, there is still room for improvement of screening and management of patients with end-stage renal disease and preparation for renal replacement therapy.

  14. Kidney Transplantation as Primary Therapy for End-Stage Renal Disease: A National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) Conference

    PubMed Central

    Abecassis, Michael; Bartlett, Stephen T.; Collins, Allan J.; Davis, Connie L.; Delmonico, Francis L.; Friedewald, John J.; Hays, Rebecca; Howard, Andrew; Jones, Edward; Leichtman, Alan B.; Merion, Robert M.; Metzger, Robert A.; Pradel, Francoise; Schweitzer, Eugene J.; Velez, Ruben L.; Gaston, Robert S.

    2008-01-01

    Background and objectives: Kidney transplantation is the most desired and cost-effective modality of renal replacement therapy for patients with irreversible chronic kidney failure (end-stage renal disease, stage 5 chronic kidney disease). Despite emerging evidence that the best outcomes accrue to patients who receive a transplant early in the course of renal replacement therapy, only 2.5% of incident patients with end-stage renal disease undergo transplantation as their initial modality of treatment, a figure largely unchanged for at least a decade. Design, setting, participants, & measurements: The National Kidney Foundation convened a Kidney Disease Outcomes Quality Initiative (KDOQI) conference in Washington, DC, March 19 through 20, 2007, to examine the issue. Fifty-two participants representing transplant centers, dialysis providers, and payers were divided into three work groups to address the impact of early transplantation on the chronic kidney disease paradigm, educational needs of patients and professionals, and finances of renal replacement therapy. Results: Participants explored the benefits of early transplantation on costs and outcomes, identified current barriers (at multiple levels) that impede access to early transplantation, and recommended specific interventions to overcome those barriers. Conclusions: With implementation of early education, referral to a transplant center coincident with creation of vascular access, timely transplant evaluation, and identification of potential living donors, early transplantation can be an option for substantially more patients with chronic kidney disease. PMID:18256371

  15. Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases

    PubMed Central

    Schwartz, Jeremy I.; Dunkle, Ashley; Akiteng, Ann R.; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K.; Mutungi, Gerald; Rabin, Tracy L.; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

    2015-01-01

    Background The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Methods Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. Results In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Discussion Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda. PMID:25563451

  16. Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases.

    PubMed

    Schwartz, Jeremy I; Dunkle, Ashley; Akiteng, Ann R; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K; Mutungi, Gerald; Rabin, Tracy L; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

    2015-01-01

    Background The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Methods Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. Results In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Discussion Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda.

  17. 78 FR 6329 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... Study to Evaluate Pregnancy exposureS (BD-STEPS), FOA DD13-003, initial review. In accordance with... received in response to ``Birth Defects Study to Evaluate Pregnancy exposureS (BD-STEPS), FOA...

  18. 78 FR 20319 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... Health Interventions in Haiti to Support Post-earthquake Reconstruction, Cholera and HIV/AIDS, FOA GH13... Haiti to Support Post-earthquake Reconstruction, Cholera and HIV/AIDS, FOA GH13- 006, initial...

  19. Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative.

    PubMed

    Ping, Peipei; Gustafsson, Åsa B; Bers, Don M; Blatter, Lothar A; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N; Wong, Renee; Schwartz Longacre, Lisa

    2015-07-17

    Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles.

  20. Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative

    PubMed Central

    Ping, Peipei; Gustafsson, Åsa B.; Bers, Don M.; Blatter, Lothar; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N.; Wong, Renee; Longacre, Lisa Schwartz

    2015-01-01

    Summary Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful completion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles. PMID:26185209

  1. Neuroimaging predictors of AED resistance in new-onset epilepsies.

    PubMed

    Cendes, Fernando

    2011-07-01

    The best prognostic factors in early-onset epilepsies are the response to the first antiepileptic drug (AED) trial, age at seizure onset, number of seizures prior to treatment, and the presence of a lesion or abnormal neurologic examination. However, early and adequate response to AED is most likely an epiphenomenon reflecting the nature of underlying epileptogenicity, which may be defined as a complex interaction of underlying pathology, genetics, and environment. Patients with the same type of epileptogenic lesion, for example, hippocampal sclerosis, may have a varying response to AED. Modern neuroimaging, in particular quantitative magnetic resonance imaging (MRI) techniques may be helpful to better understand this complex interaction of factors leading to refractoriness. Patients who respond well to AEDs have no or minor MRI abnormalities, and among those with underlying lesions there is an inverse correlation between outcome and the extent of MRI-defined neuronal damage outside the main lesion, which may be undetectable by visual analyses of routine MRI. The extent of neuronal damage appears to be related to the severity of initial precipitating injuries, probably interacts with genetic factors, and may progress over time when seizures are uncontrolled. The presence and extent of abnormalities detected by quantitative MRI may also be helpful to guide AED withdrawal in those patients who are seizure free for >2 years. Combined MRI measures may have potential clinical value for predicting AED response in near future.

  2. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    PubMed Central

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-01-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings. PMID:26229677

  3. Neuroimaging in adult penetrating brain injury: a guide for radiographers.

    PubMed

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  4. Electrical neuroimaging reveals early generator modulation to emotional words.

    PubMed

    Ortigue, Stephanie; Michel, Christoph M; Murray, Micah M; Mohr, Christine; Carbonnel, Serge; Landis, Theodor

    2004-04-01

    Functional electrical neuroimaging investigated incidental emotional word processing. Previous research suggests that the brain may differentially respond to the emotional content of linguistic stimuli pre-lexically (i.e., before distinguishing that these stimuli are words). We investigated the spatiotemporal brain mechanisms of this apparent paradox and in particular whether the initial differentiation of emotional stimuli is marked by different brain generator configurations using high-density, event-related potentials. Such would support the existence of specific cerebral resources dedicated to emotional word processing. A related issue concerns the possibility of right-hemispheric specialization in the processing of emotional stimuli. Thirteen healthy men performed a go/no-go lexical decision task with bilateral word/non-word or non-word/non-word stimulus pairs. Words included equal numbers of neutral and emotional stimuli, but subjects made no explicit discrimination along this dimension. Emotional words appearing in the right visual field (ERVF) yielded the best overall performance, although the difference between emotional and neutral words was larger for left than for right visual field presentations. Electrophysiologically, ERVF presentations were distinguished from all other conditions over the 100-140 ms period by a distinct scalp topography, indicative of different intracranial generator configurations. A distributed linear source estimation (LAURA) of this distinct scalp potential field revealed bilateral lateral-occipital sources with a right hemisphere current density maximum. These data support the existence of a specialized brain network triggered by the emotional connotation of words at a very early processing stage.

  5. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  6. Neuroimaging the temporal dynamics of human avoidance to sustained threat.

    PubMed

    Schlund, Michael W; Hudgins, Caleb D; Magee, Sandy; Dymond, Simon

    2013-11-15

    Many forms of human psychopathology are characterized by sustained negative emotional responses to threat and chronic behavioral avoidance, implicating avoidance as a potential transdiagnostic factor. Evidence from both nonhuman neurophysiological and human neuroimaging studies suggests a distributed frontal-limbic-striatal brain network supports avoidance. However, our understanding of the temporal dynamics of the network to sustained threat that prompts sustained avoidance is limited. To address this issue, 17 adults were given extensive training on a modified free-operant avoidance task in which button pressing avoided money loss during a sustained threat period. Subsequently, subjects underwent functional magnetic resonance imaging while completing the avoidance task. In our regions of interest, we observed phasic, rather than sustained, activation during sustained threat in dorsolateral and inferior frontal regions, anterior and dorsal cingulate, ventral striatum and regions associated with emotion, including the amygdala, insula, substantia nigra and bed nucleus of the stria terminalis complex. Moreover, trait levels of experiential avoidance were negatively correlated with insula, hippocampal and amygdala activation. These findings suggest knowledge that one can consistently avoid aversive outcomes is not associated with decreased threat-related responses and that individuals with greater experiential avoidance exhibit reduced reactivity to initial threat. Implications for understanding brain mechanisms supporting human avoidance and psychological theories of avoidance are discussed.

  7. The Evolution of Neuroimaging Research and Developmental Language Disorders.

    ERIC Educational Resources Information Center

    Lane, Angela B.; Foundas, Anne L.; Leonard, Christiana M.

    2001-01-01

    This article reviews current neuroimaging literature, including computer tomography, positron emission tomography, single photon emission spectroscopy, and magnetic resonance imaging, on individuals with developmental language disorders. The review suggests a complicated relationship between cortical morphometry and language development that is…

  8. Commentary on the 2016 named series: Neuroimaging, inflammation and behavior.

    PubMed

    Harrison, Neil A

    2016-11-01

    Neuroimaging techniques are increasingly used to characterize the neural circuitry mediating actions of inflammation on mood, motivation, and cognition and its relationship to common mental illnesses, particularly major depressive disorder (MDD). In addition, imaging techniques such as single photon emission tomography (SPECT), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) can index effects of inflammation on specific neurotransmitters, monoamine transporters, metabolites and even activation of discrete cells such as microglia. The special named series 'Neuroimaging, inflammation and behavior' illustrates the power of neuroimaging techniques to characterize discrete actions of inflammation on the brain at neurochemical, cellular, regional and network levels. Combined with careful cognitive assessment and pre-clinical studies, diverse neuroimaging techniques are helping clarify the mechanisms through which inflammation acts on the brain to reorient behavior and predispose to mental and physical illnesses.

  9. Neuroimaging Studies in Obsessive Compulsive Disorder: A Narrative Review

    PubMed Central

    Parmar, Arpit; Sarkar, Siddharth

    2016-01-01

    Obsessive compulsive disorder (OCD) is a relatively common psychiatric illness with a lifetime prevalence of 2–3% in general population. The pathophysiology of OCD is not yet fully understood, however over the last few decades, evidence for abnormalities of cortico-striatal-thalamic-cortico (CSTC) circuitry in etiopathogenesis of OCD has accumulated. Recent brain imaging techniques have been particularly convincing in suggesting that CSTC circuits are responsible for mediation of OCD symptoms. Neuroimaging studies, especially more recent studies using functional neuroimaging methods have looked for possible changes seen in the brain of patients with OCD, the specificity of the findings (as compared to other psychiatric illnesses) and the effects of treatment (pharmacotherapy/psychotherapy) on such changes were observed. This narrative review discusses the neuroimaging findings seen in patients with OCD with a special focus on relatively more recent neuroimaging modalities such as magnetic resonance spectroscopy and magnetoencephalography. PMID:27833219

  10. Auditory Neuroimaging with fMRI and PET

    PubMed Central

    Talavage, Thomas M.; Gonzalez-Castillo, Javier; Scott, Sophie K.

    2013-01-01

    For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging. PMID:24076424

  11. Sleep neuroimaging and models of consciousness.

    PubMed

    Tagliazucchi, Enzo; Behrens, Marion; Laufs, Helmut

    2013-01-01

    Human deep sleep is characterized by reduced sensory activity, responsiveness to stimuli, and conscious awareness. Given its ubiquity and reversible nature, it represents an attractive paradigm to study the neural changes which accompany the loss of consciousness in humans. In particular, the deepest stages of sleep can serve as an empirical test for the predictions of theoretical models relating the phenomenology of consciousness with underlying neural activity. A relatively recent shift of attention from the analysis of evoked responses toward spontaneous (or "resting state") activity has taken place in the neuroimaging community, together with the development of tools suitable to study distributed functional interactions. In this review we focus on recent functional Magnetic Resonance Imaging (fMRI) studies of spontaneous activity during sleep and their relationship with theoretical models for human consciousness generation, considering the global workspace theory, the information integration theory, and the dynamical core hypothesis. We discuss the venues of research opened by these results, emphasizing the need to extend the analytic methodology in order to obtain a dynamical picture of how functional interactions change over time and how their evolution is modulated during different conscious states. Finally, we discuss the need to experimentally establish absent or reduced conscious content, even when studying the deepest sleep stages.

  12. Challenges for Molecular Neuroimaging with MRI

    PubMed Central

    Lelyveld, Victor S.; Atanasijevic, Tatjana; Jasanoff, Alan

    2010-01-01

    Magnetic resonance (MRI)-based molecular imaging methods are beginning to have impact in neuroscience. A growing number of molecular imaging agents have been synthesized and tested in vitro, but so far relatively few have been validated in the brains of live animals. Here, we discuss key challenges associated with expanding the repertoire of successful molecular neuroimaging approaches. The difficulty of delivering agents past the blood-brain barrier (BBB) is a particular obstacle to molecular imaging in the central nervous system. We review established and emerging techniques for trans-BBB delivery, including intracranial infusion, BBB disruption, and transporter-related methods. Improving the sensitivity with which MRI-based molecular agents can be detected is a second major challenge. Better sensitivity would in turn reduce the requirements for delivery and alleviate potential side effects. We discuss recent efforts to enhance relaxivity of conventional longitudinal relaxation time (T1) and transverse relaxation time (T2) MRI contrast agents, as well as strategies that involve amplifying molecular signals or reducing endogenous background influences. With ongoing refinement of imaging approaches and brain delivery methods, MRI-based techniques for molecular-level neuroscientific investigation will fall increasingly within reach. PMID:20808721

  13. Neuroimaging revolutionizes therapeutic approaches to chronic pain

    PubMed Central

    Borsook, David; Moulton, Eric A; Schmidt, Karl F; Becerra, Lino R

    2007-01-01

    An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS. PMID:17848191

  14. Neuroimaging studies in people with gender incongruence.

    PubMed

    Kreukels, Baudewijntje P C; Guillamon, Antonio

    2016-01-01

    The current review gives an overview of brain studies in transgender people. First, we describe studies into the aetiology of feelings of gender incongruence, primarily addressing the sexual differentiation hypothesis: does the brain of transgender individuals resemble that of their natal sex, or that of their experienced gender? Findings from neuroimaging studies focusing on brain structure suggest that the brain phenotypes of trans women (MtF) and trans men (FtM) differ in various ways from control men and women with feminine, masculine, demasculinized and defeminized features. The brain phenotypes of people with feelings of gender incongruence may help us to figure out whether sex differentiation of the brain is atypical in these individuals, and shed light on gender identity development. Task-related imaging studies may show whether brain activation and task performance in transgender people is sex-atypical. Second, we review studies that evaluate the effects of cross-sex hormone treatment on the brain. This type of research provides knowledge on how changes in sex hormone levels may affect brain structure and function.

  15. Sleep Neuroimaging and Models of Consciousness

    PubMed Central

    Tagliazucchi, Enzo; Behrens, Marion; Laufs, Helmut

    2013-01-01

    Human deep sleep is characterized by reduced sensory activity, responsiveness to stimuli, and conscious awareness. Given its ubiquity and reversible nature, it represents an attractive paradigm to study the neural changes which accompany the loss of consciousness in humans. In particular, the deepest stages of sleep can serve as an empirical test for the predictions of theoretical models relating the phenomenology of consciousness with underlying neural activity. A relatively recent shift of attention from the analysis of evoked responses toward spontaneous (or “resting state”) activity has taken place in the neuroimaging community, together with the development of tools suitable to study distributed functional interactions. In this review we focus on recent functional Magnetic Resonance Imaging (fMRI) studies of spontaneous activity during sleep and their relationship with theoretical models for human consciousness generation, considering the global workspace theory, the information integration theory, and the dynamical core hypothesis. We discuss the venues of research opened by these results, emphasizing the need to extend the analytic methodology in order to obtain a dynamical picture of how functional interactions change over time and how their evolution is modulated during different conscious states. Finally, we discuss the need to experimentally establish absent or reduced conscious content, even when studying the deepest sleep stages. PMID:23717291

  16. 76 FR 59133 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    ... Immunodeficiency Virus (HIV) Prevention Projects for Young Men of Color Who Have Sex with Men and Young Transgender..., National Center for HIV, Hepatitis and Sexually Transmitted Diseases Prevention, CDC, 1600 Clifton Road,...

  17. 78 FR 19269 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    2013-03-29

    ... Committee Act (Pub.L. 92- 463). Contact Person for More Information: J. Felix Rogers, Ph.D., M.P.H..., Management Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  18. Functional neuroimaging and schizophrenia: a view towards effective connectivity modeling and polygenic risk.

    PubMed

    Birnbaum, Rebecca; Weinberger, Daniel R

    2013-09-01

    We review critical trends in imaging genetics as applied to schizophrenia research, and then discuss some future directions of the field. A plethora of imaging genetics studies have investigated the impact of genetic variation on brain function, since the paradigm of a neuroimaging intermediate phenotype for schizophrenia first emerged. It was initially posited that the effects of schizophrenia susceptibility genes would be more penetrant at the level of biologically based neuroimaging intermediate phenotypes than at the level of a complex and phenotypically heterogeneous psychiatric syndrome. The results of many studies support this assumption, most of which show single genetic variants to be associated with changes in activity of localized brain regions, as determined by select cognitive controlled tasks. From these basic studies, functional neuroimaging analysis of intermediate phenotypes has progressed to more complex and realistic models of brain dysfunction, incorporating models of functional and effective connectivity, including the modalities of psycho-physiological interaction, dynamic causal modeling, and graph theory metrics. The genetic association approaches applied to imaging genetics have also progressed to more sophisticated multivariate effects, including incorporation of two-way and three-way epistatic interactions, and most recently polygenic risk models. Imaging genetics is a unique and powerful strategy for understanding the neural mechanisms of genetic risk for complex CNS disorders at the human brain level.

  19. World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

    PubMed

    Cianciolo, R E; Mohr, F C; Aresu, L; Brown, C A; James, C; Jansen, J H; Spangler, W L; van der Lugt, J J; Kass, P H; Brovida, C; Cowgill, L D; Heiene, R; Polzin, D J; Syme, H; Vaden, S L; van Dongen, A M; Lees, G E

    2016-01-01

    Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

  20. The role of infection in inflammatory bowel disease: initiation, exacerbation and protection.

    PubMed

    Lidar, Merav; Langevitz, Pnina; Shoenfeld, Yehuda

    2009-09-01

    Inflammatory bowel disease, a collective term for ulcerative colitis and Crohn's disease, is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. The role of infection in the development of inflammatory bowel disease is underscored by various clinical observations, such as the delayed age of onset, suggesting that childhood exposure to pathogens is essential, and the clinical improvement that follows decreasing bacterial intestinal load. Over the years, many a pathogen has been linked to the development and exacerbation of inflammatory bowel disease, notably; Mycobacterium paratuberculosis, Escherichia coli, Listeria monocytogenes and Chlamydia as well as viruses such as measles, mumps, rubella, Epstein-Barr virus and cytomegalovirus. Presently, leading theories of disease pathogenesis suggest loss of immune tolerance to normal commensal bacteria coupled with excessive exposure to bacterial antigenic products. This review describes the most commonly implicated pathogens in the causation of IBD and presents the evidence supporting their pathogenic role as well as data that offset their importance.

  1. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

    PubMed

    Levey, A S; Atkins, R; Coresh, J; Cohen, E P; Collins, A J; Eckardt, K-U; Nahas, M E; Jaber, B L; Jadoul, M; Levin, A; Powe, N R; Rossert, J; Wheeler, D C; Lameire, N; Eknoyan, G

    2007-08-01

    Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

  2. Cerebral Microbleeds: A Review of Clinical, Genetic, and Neuroimaging Associations

    PubMed Central

    Yates, Paul A.; Villemagne, Victor L.; Ellis, Kathryn A.; Desmond, Patricia M.; Masters, Colin L.; Rowe, Christopher C.

    2013-01-01

    Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer’s disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using 11C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage – particularly in the setting of anticoagulation – and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future. PMID:24432010

  3. Difficulty in terminating the preceding movement/posture explains the impaired initiation of new movements in Parkinson's disease.

    PubMed

    Warabi, Tateo; Fukushima, Kikuro; Olley, Peter M; Chiba, Susumu; Yanagisawa, Nobuo

    2011-06-01

    To determine whether the difficulty of initiating volitional movements in Parkinson's disease is primarily due to impaired termination of preceding movement/posture or to impaired initiation of new movement, patients with Parkinson's disease and age-matched controls were first asked to visually fixate a stationary spot and simultaneously align wrist position accurately with it. They were then requested to make rapid movements of eyes and wrist to a test stimulus presented in the peripheral visual field. We analyzed latencies of ocular and manual movements to the test stimulus in two conditions; in the overlap task the stationary spot remained on during illumination of the test stimulus requiring subjects to terminate fixation and wrist positioning themselves to initiate new movements. In the gap task, the stationary spot was turned off 200 ms before illuminating the test stimulus. Latencies of ocular and manual movements were prolonged in the overlap task than those in the gap task. Effects of fixation/wrist positioning on the latency of new movement were evaluated by the difference in latencies between the overlap and gap tasks normalized by the latency difference of the controls. These ratios increased exponentially as Parkinson's stage increased, suggesting the latency prolongation in patients with stage III and IV Parkinson's disease under the overlap condition primarily reflected the contribution of difficulty to terminate existing fixation/wrist positioning.

  4. Cognitive neuroscience neuroimaging repository for the adult lifespan.

    PubMed

    Razlighi, Qolamreza R; Habeck, Christian; Barulli, Daniel; Stern, Yaakov

    2017-01-01

    With recent advances in neuroimaging technology, it is now possible to image human brain function in vivo, which revolutionized the cognitive neuroscience field. However, like any other newly developed technique, the acquisition of neuroimaging data is costly and logistically challenging. Furthermore, studying human cognition requires acquiring a large amount of neuroimaging data, which might not be feasible to do by every researcher in the field. Here, we describe our group's efforts to acquire one of the largest neuroimaging datasets that aims to investigate the neural substrates of age-related cognitive decline, which will be made available to share with other investigators. Our neuroimaging repository includes up to 14 different functional images for more than 486 subjects across the entire adult lifespan in addition to their 3 structural images. Currently, data from 234 participants have been acquired, including all 14 functional and 3 structural images, which is planned to increased to 375 participants in the next few years. A complete battery of neuropsychological tests was also administered to all participants. The neuroimaging and accompanying psychometric data will be available through an online and easy-to-use data sharing website.

  5. The Current Impact of Incidental Findings Found during Neuroimaging on Neurologists’ Workloads

    PubMed Central

    Booth, Thomas C.; Boyd-Ellison, Jennifer M.

    2015-01-01

    Objective Neuroimaging is an important diagnostic tool in the assessment of neurological disease, but often unmasks Incidental Findings (IFs). The negative impacts of IFs, such as ‘patient’ anxiety, present neurologists with management dilemmas, largely due to the limited knowledge base surrounding the medical significance of these IFs. In particular, the lack of evidence-based clinical trials investigating the efficacy of treatments for subclinical IFs makes management protocols challenging. The objective was to determine the impact IFs may have on neurologists’ workloads and healthcare budgets and to examine neurologists’ concerns regarding the clinical management of these ‘patients’. Methods Qualitative research based on constructivist grounded theory. Data was collected through semi-structured interviews of purposively sampled neurologists, coded, and concurrent comparative analysis performed. A substantive theory of the ‘IF impacts’ was developed after concept saturation. Results Neurologists managed the escalating workload caused by an increased number of referrals of ‘patients’ with IFs found during neuroimaging; however it was unclear whether this was sustainable in the future. Neurologists experienced IF management dilemmas and spent more time with ‘patients’ affected by anxiety. The lack of information provided to those undergoing neuroimaging by the referring clinician regarding the possibility of discovering IFs was highlighted. Conclusion The impact of IFs upon the neurologist, ‘patient’ and the health institution appeared considerable. Further research determining the natural history of subclinical IFs and the efficacy of intervention will help to alleviate these issues. PMID:25723558

  6. [Evaluation of disease management programmes--assessing methods and initial outcomes from a health economic perspective].

    PubMed

    Birnbaum, Dana Sophie; Braun, Sebastian

    2010-01-01

    Evaluation represents a substantial component of the concept of Disease Management Programmes. This and the fact that the implementation of Disease Management Programmes constitutes a major change in the German healthcare system require that the criteria established by the German Federal Social Insurance Authority (Bundesversicherungsamt) be carefully reviewed. The present paper focuses on the evaluation method and the economic data. The pre-/-post study design used in the evaluation is known to be vulnerable to threats to internal validity. The objective of this paper is to analyze whether these threats to internal validity which have been known theoretically are confirmed by the results of the final reports. A review of the final reports of health insurance companies like the AOK, Barmer and a group of the BKK in Westfalen-Lippe shows that this question can be answered in the affirmative. The pre-/-post design without control groups is unable to recognize the failure or success of the Disease Management concept. The reasons include a high drop-out rate as well as the lack of consideration of the characteristics of chronic disease. Hence the evaluation method has failed to prove the quality of Disease Management Programmes in Germany. This is why consistent further development is needed.

  7. Frosted branch angiitis, neuroretinitis as initial ocular manifestation in Behçet disease.

    PubMed

    Al-Mujaini, Abdullah; Wali, Upender K

    2011-01-01

    Behçet disease is an idiopathic, multisystem disorder characterized by recurrent episodes of orogenital ulceration and vasculitis of the veins and arteries of all calibers. Ocular involvement may affect the conjunctiva, sclera, uveal tract, vitreous, blood vessels, and retina. Many theories have pointed toward an autoimmune response behind its pathogenesis, which may be triggered by exposure to an infectious agent. Frosted branch angiitis is characterized by vascular inflammation, sheathing, retinal edema, and retinal hemorrhages. The disease may be idiopathic in a majority of the cases or may be associated with ocular and systemic pathology. Association between Behηet disease, Frosted branch angiitis, and neuroretinitis is not reported in literature. This uncommon combination reflects the varied systemic and ocular manifestations in Behçet disease, especially in patients who are not diagnosed and treated in time. We hereby report a case of bilateral frosted branch angiitis and neuroretinitis in a young male from Middle-east, suffering from Behçet disease.

  8. 77 FR 31358 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... Resident Knowledge and Practice in Physical Activity, Nutrition, and Obesity Counseling for Primary... initial review, discussion, and evaluation of ``Medical Resident Knowledge and Practice in Physical Activity, Nutrition, and Obesity Counseling for Primary Prevention of Cancer, SIP12-053, Panel C,...

  9. 78 FR 62636 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    2013-10-22

    ... Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Cooperative... the Director, Management Analysis and Services Office, CDC, pursuant to Public Law 92-463. Matters To... received in response to Cooperative Agreement on Occupational Health with the World Health...

  10. 78 FR 22268 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... Haiti to Support Post-earthquake Reconstruction, Cholera and HIV/AIDS, FOA GH13-006, initial review... Haiti to Support Post-earthquake Reconstruction, Cholera and HIV/AIDS, FOA GH13-006. Matters To Be... Assistance for Public Health Interventions in Haiti to Support Post-earthquake Reconstruction, Cholera...

  11. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... Incentive- based Smoking Cessation for Pregnant Women, FOA DP 13-003, initial review. In accordance with... of the Director, Management Analysis and Services Office, CDC, pursuant to Public Law 92-463. Matters... applications received in response to ``Cost-Benefit of Incentive-based Smoking Cessation for Pregnant...

  12. 77 FR 73662 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

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    2012-12-11

    ...): Initial Review The meeting announced below concerns Occupational Safety and Health Education and Research...., February 27, 2013 (Closed). 8:00 a.m.-12:00 p.m., February 28, 2013 (Closed). Place: Renaissance Atlanta... Health Education and Research Centers (ERC) PAR 10-217.'' Contact Person for More Information:...

  13. 76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ...-046, Panel D'', initial review. Contact Person for More Information: Brenda Colley Gilbert, PhD, M.P.H...) announces the aforementioned meeting: Time and Date: 11 a.m.-5 p.m., June 16, 2011 (Closed). Place.... BILLING CODE 4163-18-P...

  14. 77 FR 39497 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... Projects (SIPs): Nutrition and Obesity Policy Research and Evaluation Network (NOPREN)--Coordinating Center, SIP12-061 and Nutrition and Obesity Policy Research and Evaluation Network (NOPREN)--Collaborating... initial review, discussion, and evaluation of applications received in response to ``Nutrition and...

  15. Regional Initiatives in Support of Surveillance in East Africa: The East Africa Integrated Disease Surveillance Network (EAIDSNet) Experience

    PubMed Central

    Ope, Maurice; Sonoiya, Stanley; Kariuki, James; Mboera, Leonard E.G.; Gandham, Ramana N.V.; Schneidman, Miriam; Kimura, Mwihaki

    2013-01-01

    The East African Integrated Disease Surveillance Network (EAIDSNet) was formed in response to a growing frequency of cross-border malaria outbreaks in the 1990s and a growing recognition that fragmented disease interventions, coupled with weak laboratory capacity, were making it difficult to respond in a timely manner to the outbreaks of malaria and other infectious diseases. The East Africa Community (EAC) partner states, with financial support from the Rockefeller Foundation, established EAIDSNet in 2000 to develop and strengthen the communication channels necessary for integrated cross-border disease surveillance and control efforts. The objective of this paper is to review the regional EAIDSNet initiative and highlight achievements and challenges in its implementation. Major accomplishments of EAIDSNet include influencing the establishment of a Department of Health within the EAC Secretariat to support a regional health agenda; successfully completing a regional field simulation exercise in pandemic influenza preparedness; and piloting a web-based portal for linking animal and human health disease surveillance. The strategic direction of EAIDSNet was shaped, in part, by lessons learned following a visit to the more established Mekong Basin Disease Surveillance (MBDS) regional network. Looking to the future, EAIDSNet is collaborating with the East, Central and Southern Africa Health Community (ECSA-HC), EAC partner states, and the World Health Organization to implement the World Bank-funded East Africa Public Health Laboratory Networking Project (EAPHLNP). The network has also begun lobbying East African countries for funding to support EAIDSNet activities. PMID:23362409

  16. Associations between Verbal Learning Slope and Neuroimaging Markers across the Cognitive Aging Spectrum.

    PubMed

    Gifford, Katherine A; Phillips, Jeffrey S; Samuels, Lauren R; Lane, Elizabeth M; Bell, Susan P; Liu, Dandan; Hohman, Timothy J; Romano, Raymond R; Fritzsche, Laura R; Lu, Zengqi; Jefferson, Angela L

    2015-07-01

    A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2-5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation.

  17. Detecting neuroimaging biomarkers for schizophrenia: a meta-analysis of multivariate pattern recognition studies.

    PubMed

    Kambeitz, Joseph; Kambeitz-Ilankovic, Lana; Leucht, Stefan; Wood, Stephen; Davatzikos, Christos; Malchow, Berend; Falkai, Peter; Koutsouleris, Nikolaos

    2015-06-01

    Multivariate pattern recognition approaches have recently facilitated the search for reliable neuroimaging-based biomarkers in psychiatric disorders such as schizophrenia. By taking into account the multivariate nature of brain functional and structural changes as well as their distributed localization across the whole brain, they overcome drawbacks of traditional univariate approaches. To evaluate the overall reliability of neuroimaging-based biomarkers, we conducted a comprehensive literature search to identify all studies that used multivariate pattern recognition to identify patterns of brain alterations that differentiate patients with schizophrenia from healthy controls. A bivariate random-effects meta-analytic model was implemented to investigate the sensitivity and specificity across studies as well as to assess the robustness to potentially confounding variables. In the total sample of n=38 studies (1602 patients and 1637 healthy controls), patients were differentiated from controls with a sensitivity of 80.3% (95% CI: 76.7-83.5%) and a specificity of 80.3% (95% CI: 76.9-83.3%). Analysis of neuroimaging modality indicated higher sensitivity (84.46%, 95% CI: 79.9-88.2%) and similar specificity (76.9%, 95% CI: 71.3-81.6%) of rsfMRI studies as compared with structural MRI studies (sensitivity: 76.4%, 95% CI: 71.9-80.4%, specificity of 79.0%, 95% CI: 74.6-82.8%). Moderator analysis identified significant effects of age (p=0.029), imaging modality (p=0.019), and disease stage (p=0.025) on sensitivity as well as of positive-to-negative symptom ratio (p=0.022) and antipsychotic medication (p=0.016) on specificity. Our results underline the utility of multivariate pattern recognition approaches for the identification of reliable neuroimaging-based biomarkers. Despite the clinical heterogeneity of the schizophrenia phenotype, brain functional and structural alterations differentiate schizophrenic patients from healthy controls with 80% sensitivity and specificity.

  18. Rapid progressive interstitial lung disease as initial manifestation of primary Sjögren’s syndrome: a case report

    PubMed Central

    Lin, Yihua; Yi, Qun; Cheng, Deyun

    2014-01-01

    Primary Sjögren’s syndrome is a chronic inflammatory disorder with many extraglandular organ systems involved, including the lungs. Diffuse interstitial lung disease is the most serious form of lung involvement. Parenchymal lung involvement in primary Sjögren’s syndrome is usually manifested by cough and/or slowly progressive dyspnea and most of the cases present as chronic course. We describe here a case of primary Sjögren’s syndrome who presented as rapid progressive interstitial lung disease. Improvement was obtained with treatment of corticosteroids and ventilatory support at early time. To the best of our knowledge, this is the first report documenting primary Sjögren’s syndrome initially presenting as rapid progressive interstitial lung disease and it enriches our understanding of the clinical manifestations of primary Sjögren’s syndrome. PMID:25664130

  19. Oral Campylobacter species: Initiators of a subgroup of inflammatory bowel disease?

    PubMed

    Zhang, Li

    2015-08-21

    In recent years, a number of studies detected a significantly higher prevalence of Campylobacter species such as Campylobacter concisus (C. concisus) in intestinal biopsies and fecal samples collected from patients with inflammatory bowel disease (IBD) compared to controls. Most of these Campylobacter species are not of zoonotic origin but are human oral Campylobacter species. Bacterial species usually cause diseases in the location where they colonize. However, C. concisus and other oral Campylobacter species are associated with IBD occurring at the lower parts of the gastrointestinal tract, suggesting that these Campylobacter species may have unique virulence factors that are expressed in the lower parts of the gastrointestinal tract.

  20. A Group Intervention Model for Speech and Communication Skills in Patients with Parkinson's Disease: Initial Observations

    ERIC Educational Resources Information Center

    Manor, Yael; Posen, Jennie; Amir, Ofer; Dori, Nechama; Giladi, Nir

    2005-01-01

    Various speech and voice disorders affect 70% to 85% of individuals with Parkinson's disease (PD). Speech treatment is generally conducted on an individual basis, with family member involvement. Clinical experience indicates that many patients do not practice treatments at home or apply the learned techniques in everyday situations. An…

  1. 77 FR 4047 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ..., Prevention and Treatment of Influenza and Other Respiratory Infections in Ghana, IP12- 001, Studies at the Animal-Human Interface of Influenza and Other Zoonotic Diseases in Vietnam, IP12-002, The Incidence of Community Associated Influenza and Other Respiratory Infections in the United States, IP12-003,...

  2. 77 FR 25485 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-30

    ... review.'' Contact Person for More Information: Donald Blackman, Ph.D., M.P.H., Scientific Review Officer... and Date: 8:30 a.m.-5:00 p.m., May 15, 2012 (Closed). Place: The Georgian Terrace Hotel, 659 Peachtree... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  3. Cyclooxygenase and Alzheimer's disease: implications for preventive initiatives to slow the progression of clinical dementia.

    PubMed

    Pasinetti, G M.

    2001-08-01

    Industry and academia are devoting a tremendous amount of resources to the testing of anti-inflammatory drugs for the treatment of Alzheimer's disease (AD). This trend is the result of the growing consensus supporting the inflammatory hypothesis of AD. If anti-inflammatory strategies succeed in slowing the rate of disease progression, the impact on patients and families could be enormous. However, given the large number of candidates in the pool of anti-inflammatory drugs and given their widely divergent activities, it is essential to use methods which optimizes drug selection and study design. Pilot studies of anti-inflammatory regimens are useful in determining tolerability. However, these studies have limited value in estimating effective size since disease-modification, rather than symptomatic improvement, is the ultimate goal. Better understanding of the influence of inflammatory activity and the specific mechanisms which play an early role in the progression of the disease, will improve the likelihood of successfully identifying an effective anti-inflammatory treatment strategy. This review outlines directions in research that address possible contributions of cyclooxygenase (COX)-2, COX-1 and other inflammatory mediators to AD neurodegeneration. Finally, this article addresses potential interventions designed to control segments of classical inflammatory cascades in the brain in which cyclooxygenase is highly implicated. These considerations are critical to understand the role of cyclooxygenase in the clinical progression of AD.

  4. 76 FR 21748 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-18

    ... review.'' Contact Person for More Information: Lata Kumar, M.B.A., M.P.H., Scientific Review Officer... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 12 p.m.-4 p.m... 4163-18-P...

  5. 78 FR 75923 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-13

    ... For More Information: Gregory Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time And Date: 1:00 p.m.-3:00 p... 4163-18-P...

  6. 77 FR 20822 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ..., Number 42, Page 12844. The time and date should read as follows: Time and Date: 1 p.m.-3 p.m., April 16, 2012 (Closed). Contact Person for More Information: Gregory Anderson, M.P.H., M.S., Scientific Review..., Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  7. 78 FR 9055 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road NE., Mailstop E60, Atlanta... meeting: Time and Date: 11:00 a.m.-5:00 p.m., April 10, 2013 (Closed). Place: Teleconference. Status: The... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  8. 76 FR 21749 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-18

    ... review.'' Contact Person for More Information: Lata Kumar, M.B.A., M.P.H., Scientific Review Officer... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 12 p.m.-4 p.m... 4163-18-P...

  9. 76 FR 51985 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... been changed to the following. Time 12 p.m.-2 p.m., August 31, 2011 (Closed). Contact Person for More Information: Robin Hamre, M.P.H., R.D., Scientific Review Officer, Extramural Research Program Office..., Management Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  10. 78 FR 20319 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... Information: Jane Suen, Dr.P.H., M.S., M.P.H., Scientific Review Officer, CDC, 4770 Buford Highway NE...: 9:00 a.m.-6:00 p.m., May 15-16, 2013 (Closed). Place: Georgian Terrace, 659 Peachtree Street NE..., Management Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  11. 78 FR 17410 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ....S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road NE., Mailstop E60, Atlanta, Georgia... Prevention (CDC) announces the aforementioned meeting: Time and Date: 1:00 p.m.-4:00 p.m., May 8, 2013... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  12. 76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ... Colley Gilbert, PhD, M.P.H., Director, Extramural Research Program Office, National Center for Chronic... Prevention (CDC) announces the aforementioned meeting: Time and Date: 11 a.m.-5 p.m., June 14, 2011 (Closed... for Disease Control and Prevention. BILLING CODE 4163-18-P...

  13. 77 FR 291 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road NE., Mailstop E60, Atlanta... and Prevention (CDC) announces the aforementioned meeting: Time and Date: 8 a.m.-5 p.m., February 28... Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  14. 78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... Person For More Information: Gregory Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 1:00 p.m.-3:00 p... 4163-18-P...

  15. 78 FR 69683 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ...., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road NE., Mailstop E60, Atlanta, Georgia 30333... (CDC) announces the aforementioned meeting: Time And Date: 1:00 p.m.-3:00 p.m., January 14, 2014..., Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  16. 78 FR 9055 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... More Information: Gregory Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road NE... and Prevention (CDC) announces the aforementioned meeting: Time and Date: 1:00 p.m.-3:00 p.m., March..., Management Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  17. 76 FR 18555 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ... Anderson, M.S., M.P.H., Scientific Review Officer, CDC, 1600 Clifton Road, NE., Mailstop E60, Atlanta... meeting: Time and Date: 8 a.m.-5 p.m., May 17, 2011 (Closed). Place: Sheraton Gateway Hotel Atlanta... Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  18. 78 FR 23768 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-22

    ..., Ph.D., M.P.H., Scientific Review Officer, CDC, 4770 Buford Highway, NE., Mailstop F63, Atlanta... Prevention (CDC) announces the aforementioned SEP: Time and Date: 1:00 p.m.-4:00 p.m., June 18, 2013 (Closed... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  19. 78 FR 28221 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ...''. Contact Person for More Information: Donald Blackman, Ph.D., M.P.H., Scientific Review Officer, CDC, 4770... Disease Control and Prevention (CDC) announces the aforementioned SEP: Time and Date: 12:30 p.m.-5:00 p.m... 4163-18-P...

  20. 77 FR 12844 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... 77, Number 22, Page 5257. The time and date should read as follows: Time and Date: 1 p.m.-5 p.m., March 29, 2012 (Closed). Contact Person For More Information: Gregory Anderson, M.P.H., M.S., Scientific... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  1. 76 FR 18766 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ....'' Contact Person for More Information: Brenda Colley Gilbert, PhD, M.P.H., Director, Extramural Research... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 11 a.m.-5 p.m... and Prevention. BILLING CODE 4163-18-P...

  2. Nonhuman Primate Neuroimaging and Cocaine Medication Development

    PubMed Central

    Howell, Leonard L.

    2011-01-01

    Given the important role of the dopamine transporter (DAT) in the addictive properties of cocaine, the development and use of compounds that target the DAT represents a reasonable approach for the pharmacological treatment of cocaine abuse. The present report describes a series of studies conducted in nonhuman primates that evaluated the effectiveness of DAT inhibitors in reducing cocaine self-administration. In addition, drug substitution studies evaluated the abuse liability of the DAT inhibitors. PET neuroimaging studies quantified DAT occupancy at behaviorally relevant doses, characterized the time-course of drug uptake in brain, and documented drug-induced changes in cerebral blood flow as a model of brain activation. Selective DAT inhibitors were effective in reducing cocaine use but high (>70%) levels of DAT occupancy were associated with significant reductions in cocaine self-administration. The selective DAT inhibitors were reliably self-administered but rates of responding were lower than those maintained by cocaine even at higher levels of DAT occupancy. A profile of slow rate of drug uptake in brain accompanied by a gradual increase in extracellular dopamine may account for the more limited reinforcing effectiveness of the DAT inhibitors. Selective serotonin transporter (SERT) inhibitors were also effective in reducing cocaine use and blocked cocaine-induced brain activation and increases in extracellular dopamine. Co-administration of SERT inhibitors with a selective DAT inhibitor was more effective than the DAT inhibitor administered alone, even at comparable levels of DAT occupancy. The results indicate that combined inhibition of DAT and SERT may be a viable approach to treat cocaine addiction. PMID:19086766

  3. The human parental brain: in vivo neuroimaging.

    PubMed

    Swain, James E

    2011-07-01

    Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants' current and future behavior. Indeed, the parent-infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust-likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain-from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic-midbrain-limbic-paralimbic-cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health.

  4. Histopathological findings of extra-ileal manifestations at initial diagnosis of Crohn's disease-related ileitis.

    PubMed

    Brown, Ian S; Miller, Gregory C; Bettington, Mark L; Rosty, Christophe

    2016-11-01

    Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Our objective was to review the histological findings in index biopsies from the terminal ileum and other gastro-intestinal tract sites of Crohn's disease patients prior any treatment and to compare them with the findings from patients with non-specific ileitis. A total of 111 consecutive Crohn's disease cases (55 females, median age 27 years) with extra-ileal biopsies were retrospectively selected. Upper gastrointestinal inflammatory changes were found in 68 % of gastric biopsies, 60 % of oesophageal biopsies and 43 % of duodenal biopsies with no significant difference in frequency between paediatric and adult cases. Crohn's colitis was more common in paediatric cases than adult cases (85 % versus 57 %). Granuloma in at least one extra-ileal site was observed in 40 %, more frequently in paediatric cases than in adults (78 vs 27 %). Compared with Crohn's disease cases, the group of 151 non-specific ileitis cases (75 females, median age 52 years) were more likely to have normal upper and lower gastrointestinal biopsies and to show less frequent crypt architectural changes in the terminal ileum. In summary, Crohn's disease ileitis is often associated with inflammation elsewhere in the gastrointestinal tract while non-specific ileitis was infrequently associated with inflammation elsewhere for both paediatric and adult patients. These findings support the role of systematic biopsies in multiple gastrointestinal sites to help distinguishing Crohn's ileitis from non-specific ileitis in paediatric and adult population.

  5. Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's disease.

    PubMed

    O'Suilleabhain, Padraig E; Bottiglieri, Teodoro; Dewey, Richard B; Sharma, Shailja; Diaz-Arrastia, Ramon

    2004-12-01

    Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) micromol/L increased to 10.1 (3.1) micromol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L-dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 micromol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined.

  6. A practical review of the neuropathology and neuroimaging of multiple sclerosis.

    PubMed

    Matthews, Paul M; Roncaroli, Frederico; Waldman, Adam; Sormani, Maria Pia; De Stefano, Nicola; Giovannoni, Gavin; Reynolds, Richard

    2016-08-01

    The variability in the severity and clinical course of multiple sclerosis (MS) has as its basis an extreme heterogeneity in the location, nature and extent of pathology in the brain and spinal cord. Understanding the underlying neuropathology and associated pathogenetic mechanisms of the disease helps to communicate the rationale for treatment and disease monitoring to patients. Neuroimaging is an important tool for this: it allows clinicians to relate neuropathological changes to clinical presentations and to monitor the course of their disease. Here, we review MS neuropathology and its imaging correlates to provide a practical guide for using MRI to assess disease severity and treatment responses. This provides a foundation for optimal management of patients based on the principle that they show 'no evidence of disease activity'.

  7. Utilization of Telehealth Technology to Develop and Implement a Comprehensive Management Initiative for Chronic Diseases

    DTIC Science & Technology

    2011-10-01

    Diabetic eye disease is the leading cause of blindness among working-age adults, yet it is largely preventable with timely diagnosis and treatment ... Diabetic Retinopathy Study Research Group, 1981; Early Treatment Diabetic Retinopathy Research Group, 1991). Diabetes -related vision loss is often...with mydriatic seven-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) protocol photography (Bursell et al., 2001) and with dilated

  8. Utilization of Telehealth Technology to Develop and Implement a Comprehensive Management Initiative for Chronic Diseases

    DTIC Science & Technology

    2012-10-01

    significantly different from zero for both treatment groups after controlling for A1c level at the time of enrollment, age, gender, and type of diabetes [(a...disease is the leading cause of blindness among working-age adults, yet it is largely preventable with timely diagnosis and treatment ( Diabetic ...Retinopathy Study Research Group, 1981; Early Treatment Diabetic Retinopathy Research Group, 1991). Diabetes -related vision loss is often caused by a

  9. Effects of quadrat size and shape, initial epidemic conditions, and spore dispersal gradient on spatial statistics of plant disease epidemics.

    PubMed

    Xu, X M; Ridout, M S

    2000-07-01

    ABSTRACT The spatiotemporal spread of plant diseases was simulated using a stochastic model to study the effects of initial conditions (number of plants initially infected and their spatial pattern), spore dispersal gradient, and size and shape of sampling quadrats on statistics describing the spatiotemporal dynamics of epidemics. The spatial spread of disease was simulated using a half-Cauchy distribution with median dispersal distance mu (units of distance). A total of 54 different quadrat types, including 23 distinct sizes ranging from 4 to 144 plants, were used to sample the simulated epidemics. A symmetric form of the binary power law with two parameters (alpha, beta) was fitted to the sampled epidemic data using each of the 54 quadrats for each replicate simulation run. The alpha and beta estimates were highly correlated positively with each other, and their estimates were comparable to those estimated from observed epidemics. Intraclass correlation (kappa) was calculated for each quadrat type; kappa decreased exponentially with increasing quadrat size. An asymmetric form of the binary power law with three parameters (alpha (1), beta(1), beta(2)) was used to relate kappa to the disease incidence (p); beta1 was highly correlated to beta: beta1 approximately beta - 1. In general, initial conditions and quadrat size affected alpha, beta, alpha(1), beta(1), and beta(2) greatly. The parameter estimates increased as quadrat size increased, and the relationships were described well by a linear regression model on the logarithm of quadrat size with the slope or intercept parameters dependent on initial conditions and mu. Compared with initial conditions and quadrat size, the overall effects of mu and quadrat shape were generally small, although within each quadrat size and initial condition they could be substantial. Quadrat shape had the greatest effect when the quadrat was long and thin. The relationship of the index of dispersion (D) to p and quadrat size was

  10. The effect of Tai Chi exercise on gait initiation and gait performance in persons with Parkinson's disease.

    PubMed

    Amano, Shinichi; Nocera, Joe R; Vallabhajosula, Srikant; Juncos, Jorge L; Gregor, Robert J; Waddell, Dwight E; Wolf, Steven L; Hass, Chris J

    2013-11-01

    Gait dysfunction and postural instability are two debilitating symptoms in persons with Parkinson's disease (PD). Tai Chi exercise has recently gained attention as an attractive intervention for persons with PD because of its known potential to reduce falls and improve postural control, walking abilities, and safety at a low cost. The purpose of this report is to investigate the effect of Tai Chi exercise on dynamic postural control during gait initiation and gait performance in persons with idiopathic PD, and to determine whether these benefits could be replicated in two different environments, as complementary projects. In these two separate projects, a total of 45 participants with PD were randomly assigned to either a Tai Chi group or a control group. The Tai Chi groups in both projects completed a 16-week Tai Chi exercise session, while the control groups consisted of either a placebo (i.e., Qi-Gong) or non-exercise group. Tai Chi did not significantly improve Unified Parkinson's Disease Rating Scale Part III score, selected gait initiation parameters or gait performance in either project. Combined results from both projects suggest that 16 weeks of class-based Tai Chi were ineffective in improving either gait initiation, gait performance, or reducing parkinsonian disability in this subset of persons with PD. Thus the use of short-term Tai Chi exercise should require further study before being considered a valuable therapeutic intervention for these domains in PD.

  11. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

    PubMed

    Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad; Adib, Ali

    2016-01-01

    Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

  12. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease

    PubMed Central

    Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad

    2016-01-01

    Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease. PMID:27872769

  13. A neuroinformatics database system for disease-oriented neuroimaging research.

    PubMed

    Wong, Stephen T C; Hoo, Kent Soo; Cao, Xinhua; Tjandra, Donny; Fu, J C; Dillon, William P

    2004-03-01

    Clinical databases are continually growing and accruing more patient information. One of the challenges for managing this wealth of data is efficient retrieval and analysis of a broad range of image and non-image patient data from diverse data sources. This article describes the design and implementation of a new class of research data warehouse, neuroinformatics database system (NIDS), which will alleviate these problems for clinicians and researchers studying and treating patients with intractable temporal lobe epilepsy. The NIDS is a secured, multi-tier system that enables the user to gather, proofread, analyze, and store data from multiple underlying sources. In addition to data management, the NIDS provides several key functions including image analysis and processing, free text search of patient reports, construction of general queries, and on-line statistical analysis. The establishment of this integrated research database will serve as a foundation for future hypothesis-driven experiments, which could uncover previously unsuspected correlations and perhaps help to identify new and accurate predictors for image diagnosis.

  14. Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

    PubMed

    Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

    2015-09-24

    There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

  15. The impact of a community-based chronic disease prevention initiative: evaluation findings from Steps to Health King County.

    PubMed

    Cheadle, Allen; Bourcier, Emily; Krieger, James; Beery, William; Smyser, Michael; Vinh, Diana V; Lessler, Dan; Alfonsi, Lorrie

    2011-06-01

    Steps to Health King County (Steps KC; Seattle, Washington) was one of 40 community-level initiatives funded in 2003 as part of the Steps to a HealthierUS initiative. Steps KC goals included reducing the impact of chronic diseases through a comprehensive, coordinated approach and reducing health disparities due to chronic illness. Steps KC intervention activities took place on two levels: the overall Steps KC collaborative and individual funded programs. Collaborative-level activities included policy and systems change initiatives and efforts to better integrate the funded-program organizations. The funded programs ranged from group health promotion programs to intensive case management. Steps KC was successful in creating a large, diverse community collaborative and funding 14 separate programs that reached approximately 8,000 community residents with medium- and high-intensity programs of demonstrated effectiveness. Systems change initiatives within school districts and government agencies led to a greater institutional emphasis on health promotion and on partnership with communities to address health inequities.

  16. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin disease

    SciTech Connect

    Castellino, R.A.; Hoppe, R.T.; Blank, N.; Young, S.W.; Neumann, C.; Rosenberg, S.A.; Kaplan, H.S.

    1984-07-01

    One hundred twenty-one patients with newly diagnosed, previously untreated Hodgkin disease underwent abdominal and pelvic computed tomographic (CT) scanning and bipedal lymphography. These studies were followed by staging laparotomy, which included biopsy of the liver, retroperitoneal and mesenteric lymph nodes, and splenectomy. Correlation of the results of the imaging studies with the histopathologic diagnoses revealed a small - but significant - increased accuracy of lymphography compared with CT in assessing the retroperitoneal lymph nodes. The theoretical advantages of CT scanning in detecting lymphomatous deposits in lymph nodes about the celiac axis and the mesentery, or in the liver and spleen, were not confirmed.

  17. Risk factors for initial respiratory disease in United States' feedlots based on producer-collected daily morbidity counts.

    PubMed

    Sanderson, Michael W; Dargatz, David A; Wagner, Bruce A

    2008-04-01

    The incidence of initial respiratory disease was followed for 12 weeks in 122 pens of feedlot cattle, based on producer-collected daily morbidity counts. Weekly incidence density was calculated based on the number of new cases and the population at risk. Incidence density was greatest in the 1st week after arrival and decreased in following weeks. Weekly incidence rate varied between pens and over time from 0 to 27.7 cases per 100 animal weeks at risk. A negative binomial model controlling for multiple events within pens and over time was used to model effects on the number of new cases. Mixed gender groups, cattle from multiple sources and increasing distance shipped were associated with increased risk for initial respiratory morbidity. Heavier entry weight was associated with decreased morbidity risk. These factors may be useful in categorizing groups of calves into risk groups for targeted purchase and management decision making.

  18. Neurodevelopmental Precursors and Consequences of Substance Use during Adolescence: Promises and Pitfalls of Longitudinal Neuroimaging Strategies

    PubMed Central

    Fishbein, Diana H.; Rose, Emma J.; Darcey, Valerie L.; Belcher, Annabelle M.; VanMeter, John W.

    2016-01-01

    Neurocognitive and emotional regulatory deficits in substance users are often attributed to misuse; however most studies do not include a substance-naïve baseline to justify that conclusion. The etiological literature suggests that pre-existing deficits may contribute to the onset and escalation of use that are then exacerbated by subsequent use. To address this, there is burgeoning interest in conducting prospective, longitudinal neuroimaging studies to isolate neurodevelopmental precursors and consequences of adolescent substance misuse, as reflected in recent initiatives such as the NIH-led Adolescent Brain Cognitive Development (ABCD) study and the National Consortium on Alcohol and Neurodevelopment (NCANDA). To distinguish neurodevelopmental precursors from the consequences of adolescent substance use specifically, prospective, longitudinal neuroimaging studies with substance-naïve pre-adolescents are needed. The exemplar described in this article—i.e., the ongoing Adolescent Development Study (ADS)—used a targeted recruitment strategy to bolster the numbers of pre-adolescent individuals who were at increased risk of substance use (i.e., “high-risk”) in a sample that was relatively small for longitudinal studies of similar phenomena, but historically large for neuroimaging (i.e., N = 135; 11–13 years of age). At baseline participants underwent MRI testing and a large complement of cognitive and behavioral assessments along with genetics, stress physiology and interviews. The study methods include repeating these measures at three time points (i.e., baseline/Wave 1, Wave 2 and Wave 3), 18 months apart. In this article, rather than outlining specific study outcomes, we describe the breadth of the numerous complexities and challenges involved in conducting this type of prospective, longitudinal neuroimaging study and “lessons learned” for subsequent efforts are discussed. While these types of large longitudinal neuroimaging studies present a

  19. Neurodevelopmental Precursors and Consequences of Substance Use during Adolescence: Promises and Pitfalls of Longitudinal Neuroimaging Strategies.

    PubMed

    Fishbein, Diana H; Rose, Emma J; Darcey, Valerie L; Belcher, Annabelle M; VanMeter, John W

    2016-01-01

    Neurocognitive and emotional regulatory deficits in substance users are often attributed to misuse; however most studies do not include a substance-naïve baseline to justify that conclusion. The etiological literature suggests that pre-existing deficits may contribute to the onset and escalation of use that are then exacerbated by subsequent use. To address this, there is burgeoning interest in conducting prospective, longitudinal neuroimaging studies to isolate neurodevelopmental precursors and consequences of adolescent substance misuse, as reflected in recent initiatives such as the NIH-led Adolescent Brain Cognitive Development (ABCD) study and the National Consortium on Alcohol and Neurodevelopment (NCANDA). To distinguish neurodevelopmental precursors from the consequences of adolescent substance use specifically, prospective, longitudinal neuroimaging studies with substance-naïve pre-adolescents are needed. The exemplar described in this article-i.e., the ongoing Adolescent Development Study (ADS)-used a targeted recruitment strategy to bolster the numbers of pre-adolescent individuals who were at increased risk of substance use (i.e., "high-risk") in a sample that was relatively small for longitudinal studies of similar phenomena, but historically large for neuroimaging (i.e., N = 135; 11-13 years of age). At baseline participants underwent MRI testing and a large complement of cognitive and behavioral assessments along with genetics, stress physiology and interviews. The study methods include repeating these measures at three time points (i.e., baseline/Wave 1, Wave 2 and Wave 3), 18 months apart. In this article, rather than outlining specific study outcomes, we describe the breadth of the numerous complexities and challenges involved in conducting this type of prospective, longitudinal neuroimaging study and "lessons learned" for subsequent efforts are discussed. While these types of large longitudinal neuroimaging studies present a number of

  20. Protein Mis-Termination Initiates Genetic Diseases, Cancers, and Restricts Bacterial Genome Expansion.

    PubMed

    Wong, Tit-Yee; Schwartzbach, Steve D

    2015-01-01

    Protein termination is an important cellular process. Protein termination relies on the stop-codons in the mRNA interacting properly with the releasing factors on the ribosome. One third of inherited diseases, including cancers, are associated with the mutation of the stop-codons. Many pathogens and viruses are able to manipulate their stop-codons to express their virulence. The influence of stop-codons is not limited to the primary reading frame of the genes. Stop-codons in the second and third reading frames are referred as premature stop signals (PSC). Stop-codons and PSCs together are collectively referred as stop-signals. The ratios of the stop-signals (referred as translation stop-signals ratio or TSSR) of genetically related bacteria, despite their great differences in gene contents, are much alike. This nearly identical Genomic-TSSR value of genetically related bacteria may suggest that bacterial genome expansion is limited by their unique stop-signals bias. We review the protein termination process and the different types of stop-codon mutation in plants, animals, microbes, and viruses, with special emphasis on the role of PSCs in directing bacterial evolution in their natural environments. Knowing the limit of genomic boundary could facilitate the formulation of new strategies in controlling the spread of diseases and combat antibiotic-resistant bacteria.

  1. The human secretome atlas initiative: implications in health and disease conditions.

    PubMed

    Brown, Kristy J; Seol, Haeri; Pillai, Dinesh K; Sankoorikal, Binu-John; Formolo, Catherine A; Mac, Jenny; Edwards, Nathan J; Rose, Mary C; Hathout, Yetrib

    2013-11-01

    Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. This article is part of a Special Issue entitled: An Updated Secretome.

  2. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  3. Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation.

    PubMed

    Adeniji-Sofoluwe, Adenike Temitayo; Obajimi, Gbolahan Oladele; Obajimi, Millicent Olubunmi

    2015-01-01

    Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ± 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from

  4. [Morphological study of periodontal tissues in the initial stage of periodontal disease. Part 2. Analysis of morphological measurement and status of periodontal disease].

    PubMed

    Sato, H; Tawara, H; Yamaguchi, S; Lee, J H; Ishikawa, I; Masunaga, H; Nishibori, M; Hirota, Y; Matsue, M; Matsue, I

    1989-06-01

    The morphological characteristics of periodontal tissue in periodontal disease have been interpreted differently by a number of clinical observers. Many have reported that the malposition and functional malocclusion of teeth is injurious to the periodontium. We reported in Part I that a system for evaluating periodontal status was developed for the diagnosis and management of the interproximal area at the initial stage of bone resorption. The patient group consisted of 36 adults, from 21 to 55 years of age. The severity score represented the calculated loss of periodontal support tissues: loss of alveolar bone, evaluated roentgenologically, bone level and pattern in vertical and horizontal form, periodontal pocket and gingival inflammation. Because poor oral hygiene and other factors caused swelling by gingival inflammation, we obtained study specimens from patients with chronic periodontal disease after a few tooth brushing instructions, and scalings during initial therapy in order to detect initial and established pathological changes in periodontal tissue. The purpose of this study was to clarify the relationship between periodontal disease status and morphological diagnostic indicators and different degrees of harmony and disharmony in the lower jaw. In all age groups the average percentage of bone loss and intraosseous defects tended to be higher in the groups categorized as Type III and Type F, and in the area that showed a very deep concave Spee curve to the occlusal plane in Pattern D. We considered that these morphological characteristics might be of secondary importance for diagnosis. Oral local factors were the primary extrinsic factor in the pathogenesis of horizontal and vertical interproximal bone absorption in the area of the premolars and molars.

  5. The child with a cephalocele: etiology, neuroimaging, and outcome.

    PubMed

    Martínez-Lage, J F; Poza, M; Sola, J; Soler, C L; Montalvo, C G; Domingo, R; Puche, A; Ramón, F H; Azorín, P; Lasso, R

    1996-09-01

    We report a series of 46 children who were treated for one of the diverse forms of cranium bifidum during a period of 22 years. The purpose of the survey was to investigate pathogenetic factors involved in the development of cranial dysraphism and to analyze clinical and pathological factors that influence the patients' outcome. We also investigated the existence of associated intracranial anomalies, in a systematic way, using modern methods of neuroimaging, and related the findings to the patients' final results. The lesions were classified as encephalocele (n = 15), cranial meningocele (n = 3), atretic cephalocele (n = 26), cranium bifidum occultum (n = 1), and exencephaly (n = 1). There was an excess of the atretic form of cephaloceles in our series, a fact that probably reflects geographical variations described for cephaloceles in general. The location of the lesions was occipital in 29 children, parietal in 16, and temporal and frontobasal in one case each. In seven cases there was parental consanguinity. A familial history of malformations of the central nervous system was encountered in eight instances. Associated systemic abnormalities were present in 23 patients, while central nervous system anomalies were found in 36 children. Cephalocele repair was undertaken on 35 occasions. There were no surgical fatalities in the series. The mean follow-up time was of 7 years. Overall mortality for the whole group was of 17/46 or 36%. Twenty of the 29 survivors had no neurological sequelae, but only 18 children exhibited a competitive intelligence level. A good outcome was found to correlate well with: an average head size at birth, a normal initial neurological condition, operability of the lesions, and an absence of disorders of the neuronal migration. Neurological outcome depended also on the occurrence or not of hydrocephalus, while the intelligence level was mainly related to the absence of cerebral tissue within the sac of the malformation.

  6. Initial use of fast switched dual energy CT for coronary artery disease

    NASA Astrophysics Data System (ADS)

    Pavlicek, William; Panse, Prasad; Hara, Amy; Boltz, Thomas; Paden, Robert; Yamak, Didem; Licato, Paul; Chandra, Naveen; Okerlund, Darin; Dutta, Sandeep; Bhotika, Rahul; Langan, David

    2010-04-01

    Coronary CT Angiography (CTA) is limited in patients with calcified plaque and stents. CTA is unable to confidently differentiate fibrous from lipid plaque. Fast switched dual energy CTA offers certain advantages. Dual energy CTA removes calcium thereby improving visualization of the lumen and potentially providing a more accurate measure of stenosis. Dual energy CTA directly measures calcium burden (calcium hydroxyapatite) thereby eliminating a separate non-contrast series for Agatston Scoring. Using material basis pairs, the differentiation of fibrous and lipid plaques is also possible. Patency of a previously stented coronary artery is difficult to visualize with CTA due to resolution constraints and localized beam hardening artifacts. Monochromatic 70 keV or Iodine images coupled with Virtual Non-stent images lessen beam hardening artifact and blooming. Virtual removal of stainless steel stents improves assessment of in-stent re-stenosis. A beating heart phantom with 'cholesterol' and 'fibrous' phantom coronary plaques were imaged with dual energy CTA. Statistical classification methods (SVM, kNN, and LDA) distinguished 'cholesterol' from 'fibrous' phantom plaque tissue. Applying this classification method to 16 human soft plaques, a lipid 'burden' may be useful for characterizing risk of coronary disease. We also found that dual energy CTA is more sensitive to iodine contrast than conventional CTA which could improve the differentiation of myocardial infarct and ischemia on delayed acquisitions. These phantom and patient acquisitions show advantages with using fast switched dual energy CTA for coronary imaging and potentially extends the use of CT for addressing problem areas of non-invasive evaluation of coronary artery disease.

  7. Functional neuroimaging studies of the effects of psychotherapy.

    PubMed

    Beauregard, Mario

    2014-03-01

    It has been long established that psychological interventions can markedly alter patients' thinking patterns, beliefs, attitudes, emotional states, and behaviors. Little was known about the neural mechanisms mediating such alterations before the advent of functional neuroimaging techniques. Since the turn of the new millenium, several functional neuroimaging studies have been conducted to tackle this important issue. Some of these studies have explored the neural impact of various forms of psychotherapy in individuals with major depressive disorder. Other neuroimaging studies have investigated the effects of psychological interventions for anxiety disorders. I review these studies in the present article, and discuss the putative neural mechanisms of change in psychotherapy. The findings of these studies suggest that mental and behavioral changes occurring during psychotherapeutic interventions can lead to a normalization of functional brain activity at a global level.

  8. Machine learning for neuroimaging with scikit-learn.

    PubMed

    Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael; Gervais, Philippe; Mueller, Andreas; Kossaifi, Jean; Gramfort, Alexandre; Thirion, Bertrand; Varoquaux, Gaël

    2014-01-01

    Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g., multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g., resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain.

  9. Image analysis and statistical inference in neuroimaging with R.

    PubMed

    Tabelow, K; Clayden, J D; de Micheaux, P Lafaye; Polzehl, J; Schmid, V J; Whitcher, B

    2011-04-15

    R is a language and environment for statistical computing and graphics. It can be considered an alternative implementation of the S language developed in the 1970s and 1980s for data analysis and graphics (Becker and Chambers, 1984; Becker et al., 1988). The R language is part of the GNU project and offers versions that compile and run on almost every major operating system currently available. We highlight several R packages built specifically for the analysis of neuroimaging data in the context of functional MRI, diffusion tensor imaging, and dynamic contrast-enhanced MRI. We review their methodology and give an overview of their capabilities for neuroimaging. In addition we summarize some of the current activities in the area of neuroimaging software development in R.

  10. Neuroethics, neuroimaging, and disorders of consciousness: promise or peril?

    PubMed

    Fins, Joseph J

    2011-01-01

    The advent of powerful neuroimaging tools such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has begun to redefine how we diagnose, define, and understand disorders of consciousness such as the vegetative and minimally conscious states. In my paper, I review how research using these methods is both elucidating these brain states and creating diagnostic dilemmas related to their classification as the specificity and sensitivity of traditional behavior-based assessments are weighed against sensitive but not yet fully validated neuroimaging data. I also consider how these methods are being studied as potential communication vectors for therapeutic use in subjects who heretofore have been thought to be unresponsive or minimally conscious. I conclude by considering the ethical challenges posed by novel diagnostic and therapeutic neuroimaging applications and contextualize these scientific developments against the broader needs of patients and families touched by severe brain injury.

  11. Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease.

    PubMed

    Mulay, Shrikant R; Eberhard, Jonathan N; Desai, Jyaysi; Marschner, Julian A; Kumar, Santhosh V R; Weidenbusch, Marc; Grigorescu, Melissa; Lech, Maciej; Eltrich, Nuru; Müller, Lisa; Hans, Wolfgang; Hrabě de Angelis, Martin; Vielhauer, Volker; Hoppe, Bernd; Asplin, John; Burzlaff, Nicolai; Herrmann, Martin; Evan, Andrew; Anders, Hans-Joachim

    2017-03-01

    Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.

  12. Enhancing patient engagement in chronic disease self-management support initiatives in Australia: the need for an integrated approach.

    PubMed

    Jordan, Joanne E; Briggs, Andrew M; Brand, Caroline A; Osborne, Richard H

    2008-11-17

    Although emphasis on the prevention of chronic disease is important, governments in Australia need to balance this with continued assistance to the 77% of Australians reported to have at least one long-term medical condition. Self-management support is provided by health care and community services to enhance patients' ability to care for their chronic conditions in a cooperative framework. In Australia, there is a range of self-management support initiatives that have targeted patients (most notably, chronic disease self-management education programs) and health professionals (financial incentives, education and training). To date, there has been little coordination or integration of these self-management initiatives to enhance the patient-health professional clinical encounter. If self-management support is to work, there is a need to better understand the infrastructure, systems and training that are required to engage the key stakeholders - patients, carers, health professionals, and health care organisations. A coordinated approach is required in implementing these elements within existing and new health service models to enhance uptake and sustainability.

  13. Viral Genome-Linked Protein (VPg) Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV).

    PubMed

    Zhu, Jie; Wang, Binbin; Miao, Qiuhong; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Guo, Huimin; Liu, Guangqing

    2015-01-01

    Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  14. Depression Screening in Chronic Disease Management: A Worksite Health Promotion Initiative.

    PubMed

    Jensen, Elizabeth; Dumas, Bonnie P; Edlund, Barbara J

    2016-03-01

    This pilot project aimed to improve depression symptoms and quality-of-life measures for individuals in a worksite disease management program. Two hundred forty-three individuals were invited to participate, out of which 69 enrolled. The participants had a history of diabetes, hypertension, or hyperlipidemia, and demonstrated depression using the Patient Health Questionnaire-9 (PHQ-9). The project consisted of counseling sessions provided every 2 to 4 weeks by a family nurse practitioner. PHQ-9 scores and those of an instrument that measures quality of life, the Veteran's Rand-12 (VR-12), were compared pre-intervention and post-intervention to evaluate the effectiveness of the project. PHQ-9 and VR-12 Mental Health Component (MHC) scores improved significantly after 3 months of nurse practitioner-led individual counseling sessions. This project demonstrated that depression screening and therapeutic management, facilitated by a nurse practitioner, can improve depression and perceived quality of life in individuals with hypertension, hyperlipidemia, or type 2 diabetes.

  15. [A case of Creutzfeldt-Jakob disease presenting with arm levitation as an initial symptom].

    PubMed

    Kamogawa, Kenji; Ninomiya, Satoko; Okuda, Shinya; Matsumoto, Yushi; Tomita, Hitomi; Okamoto, Kensho; Okuda, Bungo

    2014-01-01

    A 74-year-old, right handed man, developed insidiously with levitation and clumsiness of the right upper limb. His right arm tended to levitate spontaneously, when he was examined. He could put the elevated arm down on command, while the arm resumed to antigravity posture when his attention was diverted. His right arm also exhibited unwilled elevation when performing complex finger movements on the right side. He had a feeling of strangeness of the elevated limb, especially with the eyes closed. In addition to asymmetric limb-kinetic apraxia, combined sensations such as stereognosis were disturbed on the right side. Brain MRI showed high signal lesions predominantly in the left cerebral cortices and basal ganglia. SPECT with (123)I-IMP revealed asymmetric hypoperfusion, predominantly in the left medial frontal and parietal regions. Two months after the onset, levitation of the arm gradually disappeared, with the development of rapidly progressive dementia, frontal signs, dystonia and generalized myoclonus. The diagnosis of Creutzfeldt-Jakob disease (CJD) was made based on the clinical features and cerebrospinal fluid biomarkers. The early manifestation of the patient mimicked corticobasal degeneration which presents with arm levitation or alien hand syndrome. It is suggested that CJD can represent involuntary movements with higher brain dysfunction resembling corticobasal degeneration at the early stage of the illness. Although the underlying mechanism of arm levitation is still unknown, frontal disinhibition and parietal cortical sensory disturbance may contribute to the development of involuntary arm levitation in our patient.

  16. Medical Management of Parkinson's Disease after Initiation of Deep Brain Stimulation.

    PubMed

    Fasano, Alfonso; Appel-Cresswell, Silke; Jog, Mandar; Zurowkski, Mateusz; Duff-Canning, Sarah; Cohn, Melanie; Picillo, Marina; Honey, Christopher R; Panisset, Michel; Munhoz, Renato Puppi

    2016-09-01

    In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate). As for the psychiatric problems so frequently reported in PD patients, researchers have directed their attention to the complex interplay between stimulation and reduction of dopaminergic drugs only recently. In conclusion, studies addressing medical management following DBS are still needed and will certainly contribute to the ultimate success of DBS procedures.

  17. Interactions between Global Health Initiatives and Country Health Systems: The Case of a Neglected Tropical Diseases Control Program in Mali

    PubMed Central

    Cavalli, Anna; Bamba, Sory I.; Traore, Mamadou N.; Boelaert, Marleen; Coulibaly, Youssouf; Polman, Katja; Pirard, Marjan; Van Dormael, Monique

    2010-01-01

    Background Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. Methods and Findings Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local

  18. Effects of initial epidemic conditions, sporulation rate, and spore dispersal gradient on the spatio-temporal dynamics of plant disease epidemics.

    PubMed

    Xu, X M; Ridout, M S

    1998-10-01

    ABSTRACT A stochastic model that simulates the spread of disease over space and time was developed to study the effects of initial epidemic conditions (number of initial inocula and their spatial pattern), sporulation rate, and spore dispersal gradient on the spatio-temporal dynamics of plant disease epidemics. The spatial spread of disease was simulated using a half-Cauchy distribution with median dispersal distance mu (units of distance). The rate of temporal increase in disease incidence (beta(I), per day) was influenced jointly by mu and by the sporulation rate lambda (spores per lesion per day). The relationship between beta(I) and mu was nonlinear: the increase in beta(I) with increasing mu was greatest when mu was small (i.e., when the dispersal gradient was steep). The rate of temporal increase in disease severity of diseased plants (beta(S)) was affected mainly by lambda: beta(S) increased directly with increasing lambda. Intraclass correlation (kappa(t)), the correlation of disease status of plants within quadrats, increased initially with disease incidence, reached a peak, and then declined as disease incidence approached 1.0. This relationship was well described by a power-law model that is consistent with the binary form of the variance power law. The amplitude of the model relating kappa(t) to disease incidence was affected mainly by mu: kappa(t) decreased with increasing mu. The shape of the curve was affected mainly by initial conditions, especially the spatial pattern of the initial inocula. Generally, the relationship of spatial autocorrelation (rho(t,k)), the correlation of disease status of plants at various distances apart, to disease incidence and distance was well described by a four-parameter power-law model. rho(t,k) increased with disease incidence to a maximum and then declined at higher values of disease incidence, in agreement with a power-law relationship. The amplitude of rho(t,k) was determined mainly by initial conditions and by mu

  19. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based

  20. Cause and Consequence: Mitochondrial Dysfunction Initiates and Propagates Neuronal Dysfunction, Neuronal Death and Behavioral Abnormalities in Age Associated Neurodegenerative Diseases

    PubMed Central

    Gibson, Gary E.; Starkov, Anatoly; Blass, John P.; Ratan, Rajiv R.; Beal, M. Flint

    2009-01-01

    SUMMARY Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sub lethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the α-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhance ROS production in Alzheimer’s Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington’s Disease (HD), a movement disorder with cognitive features distinct form AD, complex II + III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a cross linking enzymes that can modulate transcrption, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic

  1. Neuroimaging the interaction of mind and metabolism in humans

    PubMed Central

    D’Agostino, Alexandra E.; Small, Dana M.

    2012-01-01

    Hormonal and metabolic signals interact with neural circuits orchestrating behavior to guide food intake. Neuroimaging techniques such as functional magnetic resonance imaging (fMRI) enable the identification of where in the brain particular mental processes like desire, satiety and pleasure occur. Once these neural circuits are described it then becomes possible to determine how metabolic and hormonal signals can alter brain response to influence psychological states and decision-making processes to guide intake. Here, we provide an overview of the contributions of functional neuroimaging to the understanding of how subjective and neural responses to food and food cues interact with metabolic/hormonal factors. PMID:24024114

  2. Scanning the horizon: towards transparent and reproducible neuroimaging research.

    PubMed

    Poldrack, Russell A; Baker, Chris I; Durnez, Joke; Gorgolewski, Krzysztof J; Matthews, Paul M; Munafò, Marcus R; Nichols, Thomas E; Poline, Jean-Baptiste; Vul, Edward; Yarkoni, Tal

    2017-02-01

    Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, concerns have recently been raised that the conclusions that are drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors and a lack of direct replication apply to many fields, but perhaps particularly to functional MRI. Here, we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful and reliable answers to neuroscientific questions.

  3. Incidental Findings in Neuroimaging: Ethical and Medicolegal Considerations.

    PubMed

    Leung, Lawrence

    2013-01-01

    With the rapid advances in neurosciences in the last three decades, there has been an exponential increase in the use of neuroimaging both in basic sciences and clinical research involving human subjects. During routine neuroimaging, incidental findings that are not part of the protocol or scope of research agenda can occur and they often pose a challenge as to how they should be handled to abide by the medicolegal principles of research ethics. This paper reviews the issue from various ethical (do no harm, general duty to rescue, and mutual benefits and owing) and medicolegal perspectives (legal liability, fiduciary duties, Law of Tort, and Law of Contract) with a suggested protocol of approach.

  4. The Cellie Coping Kit for Sickle Cell Disease: Initial acceptability and feasibility

    PubMed Central

    Marsac, Meghan L.; Klingbeil, Olivia G.; Hildenbrand, Aimee K.; Alderfer, Melissa A.; Kassam-Adams, Nancy; Smith-Whitley, Kim; Barakat, Lamia P.

    2014-01-01

    Sickle Cell Disease (SCD) and its treatment can place physical and psychosocial strain on children and their families, underlining the need for behavioral and emotional support. Much of SCD is often managed at home, which may prevent children from obtaining supportive services from medical and psychosocial teams. Children with SCD report a restricted number of coping strategies specific to managing SCD and may benefit from education on adaptive coping. To address this unmet need, a coping tool for children with cancer (Cellie Cancer Coping Kit) was adapted for children with SCD. The Cellie Coping Kit for SCD (Cellie Coping Kit) includes a stuffed “Cellie” toy, coping cards for children, and a book for caregivers. This study sought to assess the acceptability and feasibility of an intervention utilizing the Cellie Coping Kit. Fifteen children with SCD (ages 6-14) and their caregivers participated in a baseline assessment including semi-structured interviews to examine SCD-related stressors and coping strategies. Next, families received a brief introduction to the Cellie Coping Kit and were provided with a kit to use independently over the next four weeks before completing a follow-up assessment. Results indicated strong intervention acceptability overall. While families reported using and learning information and skills from the Cellie Coping Kit, several challenges were identified (e.g., child's living situation, busy schedules). The Cellie Coping Kit is a promising tool to support children with SCD and their families. Future research should examine whether use of the Cellie Coping Kit impacts behavioral change and improved health outcomes. PMID:25664228

  5. Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice.

    PubMed Central

    Blay, R.; Simpson, K.; Leslie, K.; Huber, S.

    1989-01-01

    DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect. Images Figure 1 PMID:2573284

  6. Analysis of a Parent-Initiated Social Media Campaign for Hirschsprung’s Disease

    PubMed Central

    Wittmeier, Kristy; Holland, Cindy; Hobbs-Murison, Kendall; Crawford, Elizabeth; Beauchamp, Chad; Milne, Brodie; Morris, Melanie

    2014-01-01

    Background Social media can be particularly useful for patients or families affected by rare conditions by allowing individuals to form online communities across the world. Objective Our aim in this study was to conduct a descriptive and quantitative analysis of the use of a social media community for Hirschsprung’s Disease (HD). Methods In July 2011, a mother of a child with HD launched the “Shit Happens” campaign. The campaign uses social media (blogs, Twitter, and Facebook) to engage other families affected by HD. Internet analytics including Google Analytics and Facebook Insights were used to evaluate the reach and responsiveness of this campaign. Results On the day the HD campaign was launched, 387 people viewed the blog “Roo’s Journey”. Blog views have now exceeded 5400 views from 37 countries. The Facebook page extends to 46 countries, has an average post reach of 298 users, 1414 “likes”, and an overall reach of 131,032 users. The campaign has 135 Twitter followers and 344 tweets at the time of writing. The most common question posted on the Facebook page is related to treatment for extreme diaper rash. Responsiveness assessment demonstrated that within 2 hours of posting, a question could receive 143 views and 20 responses, increasing to 30 responses after 5 hours. Conclusions Social media networks are well suited to discussion, support, and advocacy for health-related conditions and can be especially important in connecting families affected by rare conditions. The HD campaign demonstrates the reach and responsiveness of a community that primarily relies on social media to connect families affected by HD. Although responsive, this community is currently lacking consistent access to evidence-based guidance for their common concerns. We will explore innovative consumer-researcher partnerships to offer a solution in future research. PMID:25499427

  7. The benefit of consolidation radiotherapy to initial disease bulk in patients with advanced Hodgkin’s disease who achieved complete remission after standard chemotherapy

    PubMed Central

    Bayoumi, Yasser; Al-Homaidi, Abdulaziz; Zaidi, Syed; Tailor, Imran; Motiabi, Ibrahiem; Alshehri, Nawal; Al-Ghazali, Assem; Almudaibigh, Samer

    2015-01-01

    Background/purpose The aim of this study was to evaluate the role of consolidation radiotherapy (RT) in advanced-stage Hodgkin’s disease (HD) with initial bulky sites after radiological complete remission (CR) or partial response (PR) with positron emission tomography-negative (metabolic CR) following standard chemotherapy (ABVD [Adriamycin, bleomycin, vinblastine, and dacarbazine]) six to eight cycles. Patients and methods Adult patients with advanced-stage HD treated at our institute during the period 2006 to 2012 were retrospectively evaluated. One hundred and ninety-two patients with initial bulky disease size (>7 cm) who attained radiological CR/PR and metabolic CR were included in the analysis. One hundred and thirteen patients who received radiotherapy (RT) as consolidation postchemotherapy (RT group) were compared to 79 patients who did not receive RT (non-RT group). Disease-free (DFS) and overall survival (OS) rates were estimated using the Kaplan–Meier method and were compared according to treatment group by the log-rank tests at P ≤0.05 significance level. Results The mean age of the cohort was 33 (range: 14 to 81) years. Eighty-four patients received involved-field radiation and 29 patients received involved-site RT. The RT group had worse prognostic factors compared to the non-RT group. Thirteen (12%) relapses occurred in the RT group, and 19 (24%) relapses occurred in the non-RT group. Nine patients (8%) in the RT group died, compared to eleven patients (14%) in the non-RT group. Second malignancies were seen in only five patients: three patients in the RT group compared to two patients in the non-RT group. At 5 years, overall DFS was 79%±9% and OS was 85%±9%. There was significant statistical difference between the RT group and the non-RT group regarding 5-year DFS: 86%±7% and 74%±9%, respectively (P ≤0.02). However, the 5-year OS was 90%±5% for the RT group and 83%±8% for the non-RT group, with no statistical difference (P ≤0

  8. Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD).

    PubMed

    Gao, Ying; Erokwu, Bernadette O; DeSantis, David A; Croniger, Colleen M; Schur, Rebecca M; Lu, Lan; Mariappuram, Jose; Dell, Katherine M; Flask, Chris A

    2016-01-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T1 relaxation time results were obtained for five PCK rats at 3 months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0 T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T1 values (mean ± standard deviation = 935 ± 39 ms) compared with age-matched SD control rats (847 ± 26 ms, p = 0.01). One PCK rat exhibited severe cholangitis (mean T1  = 1413 ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent (R = 0.85, p = 0.002), periportal fibrosis area percent (R = 0.82, p = 0.004), and hydroxyproline content (R = 0.76, p = 0.01). These results suggest that hepatic T1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease.

  9. Contributions and complexities from the use of in vivo animal models to improve understanding of human neuroimaging signals

    PubMed Central

    Martin, Chris

    2014-01-01

    Many of the major advances in our understanding of how functional brain imaging signals relate to neuronal activity over the previous two decades have arisen from physiological research studies involving experimental animal models. This approach has been successful partly because it provides opportunities to measure both the hemodynamic changes that underpin many human functional brain imaging techniques and the neuronal activity about which we wish to make inferences. Although research into the coupling of neuronal and hemodynamic responses using animal models has provided a general validation of the correspondence of neuroimaging signals to specific types of neuronal activity, it is also highlighting the key complexities and uncertainties in estimating neural signals from hemodynamic markers. This review will detail how research in animal models is contributing to our rapidly evolving understanding of what human neuroimaging techniques tell us about neuronal activity. It will highlight emerging issues in the interpretation of neuroimaging data that arise from in vivo research studies, for example spatial and temporal constraints to neuroimaging signal interpretation, or the effects of disease and modulatory neurotransmitters upon neurovascular coupling. We will also give critical consideration to the limitations and possible complexities of translating data acquired in the typical animals models used in this area to the arena of human fMRI. These include the commonplace use of anesthesia in animal research studies and the fact that many neuropsychological questions that are being actively explored in humans have limited homologs within current animal models for neuroimaging research. Finally we will highlighting approaches, both in experimental animals models (e.g. imaging in conscious, behaving animals) and human studies (e.g. combined fMRI-EEG), that mitigate against these challenges. PMID:25191214

  10. Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder

    PubMed Central

    McGrath, Callie L.; Kelley, Mary E.; Holtzheimer, Paul E.; Dunlop, Boadie W.; Craighead, W. Edward; Franco, Alexandre R.; Craddock, R. Cameron; Mayberg, Helen S.

    2015-01-01

    IMPORTANCE Currently, fewer than 40% of patients treated for major depressive disorder achieve remission with initial treatment. Identification of a biological marker that might improve these odds could have significant health and economic impact. OBJECTIVE To identify a candidate neuroimaging “treatment-specific biomarker” that predicts differential outcome to either medication or psychotherapy. DESIGN Brain glucose metabolism was measured with positron emission tomography prior to treatment randomization to either escitalopram oxalate or cognitive behavior therapy for 12 weeks. Patients who did not remit on completion of their phase 1 treatment were offered enrollment in phase 2 comprising an additional 12 weeks of treatment with combination escitalopram and cognitive behavior therapy. SETTING Mood and anxiety disorders research program at an academic medical center. PARTICIPANTS Men and women aged 18 to 60 years with currently untreated major depressive disorder. INTERVENTION Randomized assignment to 12 weeks of treatment with either escitalopram oxalate (10–20 mg/d) or 16 sessions of manual-based cognitive behavior therapy. MAIN OUTCOME AND MEASURE Remission, defined as a 17-item Hamilton Depression Rating Scale score of 7 or less at both weeks 10 and 12, as assessed by raters blinded to treatment. RESULTS Positive and negative predictors of remission were identified with a 2-way analysis of variance treatment (escitalopram or cognitive behavior therapy) × outcome (remission or nonresponse) interaction. Of 65 protocol completers, 38 patients with clear outcomes and usable positron emission tomography scans were included in the primary analysis: 12 remitters to cognitive behavior therapy, 11 remitters to escitalopram, 9 nonresponders to cognitive behavior therapy, and 6 nonresponders to escitalopram. Six limbic and cortical regions were identified, with the right anterior insula showing the most robust discriminant properties across groups (effect size

  11. Perceived Utility of the RE-AIM Framework for Health Promotion/Disease Prevention Initiatives for Older Adults: A Case Study from the U.S. Evidence-Based Disease Prevention Initiative

    PubMed Central

    Ory, Marcia G.; Altpeter, Mary; Belza, Basia; Helduser, Janet; Zhang, Chen; Smith, Matthew Lee

    2015-01-01

    Dissemination and implementation (D&I) frameworks are increasingly being promoted in public health research. However, less is known about their uptake in the field, especially for diverse sets of programs. Limited questionnaires exist to assess the ways that frameworks can be utilized in program planning and evaluation. We present a case study from the United States that describes the implementation of the RE-AIM framework by state aging services providers and public health partners and a questionnaire that can be used to assess the utility of such frameworks in practice. An online questionnaire was developed to capture community perspectives about the utility of the RE-AIM framework. Distributed to project leads in 27 funded states in an evidence-based disease prevention initiative for older adults, 40 key stakeholders responded representing a 100% state-participation rate among the 27 funded states. Findings suggest that there is perceived utility in using the RE-AIM framework when evaluating grand-scale initiatives for older adults. The RE-AIM framework was seen as useful for planning, implementation, and evaluation with relevance for evaluators, providers, community leaders, and policy makers. Yet, the uptake was not universal, and some respondents reported difficulties in use, especially adopting the framework as a whole. This questionnaire can serve as the basis to assess ways the RE-AIM framework can be utilized by practitioners in state-wide D&I efforts. Maximal benefit can be derived from examining the assessment of RE-AIM-related knowledge and confidence as part of a continual quality assurance process. We recommend such an assessment be performed before the implementation of new funding initiatives and throughout their course to assess RE-AIM uptake and to identify areas for technical assistance. PMID:25964897

  12. Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

    PubMed Central

    Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

    2016-01-01

    Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

  13. CBRAIN: a web-based, distributed computing platform for collaborative neuroimaging research

    PubMed Central

    Sherif, Tarek; Rioux, Pierre; Rousseau, Marc-Etienne; Kassis, Nicolas; Beck, Natacha; Adalat, Reza; Das, Samir; Glatard, Tristan; Evans, Alan C.

    2014-01-01

    The Canadian Brain Imaging Research Platform (CBRAIN) is a web-based collaborative research platform developed in response to the challenges raised by data-heavy, compute-intensive neuroimaging research. CBRAIN offers transparent access to remote data sources, distributed computing sites, and an array of processing and visualization tools within a controlled, secure environment. Its web interface is accessible through any modern browser and uses graphical interface idioms to reduce the technical expertise required to perform large-scale computational analyses. CBRAIN's flexible meta-scheduling has allowed the incorporation of a wide range of heterogeneous computing sites, currently including nine national research High Performance Computing (HPC) centers in Canada, one in Korea, one in Germany, and several local research servers. CBRAIN leverages remote computing cycles and facilitates resource-interoperability in a transparent manner for the end-user. Compared with typical grid solutions available, our architecture was designed to be easily extendable and deployed on existing remote computing sites with no tool modification, administrative intervention, or special software/hardware configuration. As October 2013, CBRAIN serves over 200 users spread across 53 cities in 17 countries. The platform is built as a generic framework that can accept data and analysis tools from any discipline. However, its current focus is primarily on neuroimaging research and studies of neurological diseases such as Autism, Parkinson's and Alzheimer's diseases, Multiple Sclerosis as well as on normal brain structure and development. This technical report presents the CBRAIN Platform, its current deployment and usage and future direction. PMID:24904400

  14. Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE

    PubMed Central

    Sundman, Mark; Doraiswamy, P. Murali; Morey, Rajendra A.

    2015-01-01

    Traumatic brain injury (TBI) has been increasingly accepted as a major external risk factor for neurodegenerative morbidity and mortality. Recent evidence indicates that the resultant chronic neurobiological sequelae following head trauma may, at least in part, contribute to a pathologically distinct disease known as Chronic Traumatic Encephalopathy (CTE). The clinical manifestation of CTE is variable, but the symptoms of this progressive disease include impaired memory and cognition, affective disorders (i.e., impulsivity, aggression, depression, suicidality, etc.), and diminished motor control. Notably, mounting evidence suggests that the pathology contributing to CTE may be caused by repetitive exposure to subconcussive hits to the head, even in those with no history of a clinically evident head injury. Given the millions of athletes and military personnel with potential exposure to repetitive subconcussive insults and TBI, CTE represents an important public health issue. However, the incidence rates and pathological mechanisms are still largely unknown, primarily due to the fact that there is no in vivo diagnostic tool. The primary objective of this manuscript is to address this limitation and discuss potential neuroimaging modalities that may be capable of diagnosing CTE in vivo through the detection of tau and other known pathological features. Additionally, we will discuss the challenges of TBI research, outline the known pathology of CTE (with an emphasis on Tau), review current neuroimaging modalities to assess the potential routes for in vivo diagnosis, and discuss the future directions of CTE research. PMID:26441507

  15. Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE.

    PubMed

    Sundman, Mark; Doraiswamy, P Murali; Morey, Rajendra A

    2015-01-01

    Traumatic brain injury (TBI) has been increasingly accepted as a major external risk factor for neurodegenerative morbidity and mortality. Recent evidence indicates that the resultant chronic neurobiological sequelae following head trauma may, at least in part, contribute to a pathologically distinct disease known as Chronic Traumatic Encephalopathy (CTE). The clinical manifestation of CTE is variable, but the symptoms of this progressive disease include impaired memory and cognition, affective disorders (i.e., impulsivity, aggression, depression, suicidality, etc.), and diminished motor control. Notably, mounting evidence suggests that the pathology contributing to CTE may be caused by repetitive exposure to subconcussive hits to the head, even in those with no history of a clinically evident head injury. Given the millions of athletes and military personnel with potential exposure to repetitive subconcussive insults and TBI, CTE represents an important public health issue. However, the incidence rates and pathological mechanisms are still largely unknown, primarily due to the fact that there is no in vivo diagnostic tool. The primary objective of this manuscript is to address this limitation and discuss potential neuroimaging modalities that may be capable of diagnosing CTE in vivo through the detection of tau and other known pathological features. Additionally, we will discuss the challenges of TBI research, outline the known pathology of CTE (with an emphasis on Tau), review current neuroimaging modalities to assess the potential routes for in vivo diagnosis, and discuss the future directions of CTE research.

  16. CBRAIN: a web-based, distributed computing platform for collaborative neuroimaging research.

    PubMed

    Sherif, Tarek; Rioux, Pierre; Rousseau, Marc-Etienne; Kassis, Nicolas; Beck, Natacha; Adalat, Reza; Das, Samir; Glatard, Tristan; Evans, Alan C

    2014-01-01

    The Canadian Brain Imaging Research Platform (CBRAIN) is a web-based collaborative research platform developed in response to the challenges raised by data-heavy, compute-intensive neuroimaging research. CBRAIN offers transparent access to remote data sources, distributed computing sites, and an array of processing and visualization tools within a controlled, secure environment. Its web interface is accessible through any modern browser and uses graphical interface idioms to reduce the technical expertise required to perform large-scale computational analyses. CBRAIN's flexible meta-scheduling has allowed the incorporation of a wide range of heterogeneous computing sites, currently including nine national research High Performance Computing (HPC) centers in Canada, one in Korea, one in Germany, and several local research servers. CBRAIN leverages remote computing cycles and facilitates resource-interoperability in a transparent manner for the end-user. Compared with typical grid solutions available, our architecture was designed to be easily extendable and deployed on existing remote computing sites with no tool modification, administrative intervention, or special software/hardware configuration. As October 2013, CBRAIN serves over 200 users spread across 53 cities in 17 countries. The platform is built as a generic framework that can accept data and analysis tools from any discipline. However, its current focus is primarily on neuroimaging research and studies of neurological diseases such as Autism, Parkinson's and Alzheimer's diseases, Multiple Sclerosis as well as on normal brain structure and development. This technical report presents the CBRAIN Platform, its current deployment and usage and future direction.

  17. PRoNTo: pattern recognition for neuroimaging toolbox.

    PubMed

    Schrouff, J; Rosa, M J; Rondina, J M; Marquand, A F; Chu, C; Ashburner, J; Phillips, C; Richiardi, J; Mourão-Miranda, J

    2013-07-01

    In the past years, mass univariate statistical analyses of neuroimaging data have been complemented by the use of multivariate pattern analyses, especially based on machine learning models. While these allow an increased sensitivity for the detection of spatially distributed effects compared to univariate techniques, they lack an established and accessible software framework. The goal of this work was to build a toolbox comprising all the necessary functionalities for multivariate analyses of neuroimaging data, based on machine learning models. The "Pattern Recognition for Neuroimaging Toolbox" (PRoNTo) is open-source, cross-platform, MATLAB-based and SPM compatible, therefore being suitable for both cognitive and clinical neuroscience research. In addition, it is designed to facilitate novel contributions from developers, aiming to improve the interaction between the neuroimaging and machine learning communities. Here, we introduce PRoNTo by presenting examples of possible research questions that can be addressed with the machine learning framework implemented in PRoNTo, and cannot be easily investigated with mass univariate statistical analysis.

  18. Neuroimaging Research with Children: Ethical Issues and Case Scenarios

    ERIC Educational Resources Information Center

    Coch, Donna

    2007-01-01

    There are few available resources for learning and teaching about ethical issues in neuroimaging research with children, who constitute a special and vulnerable population. Here, a brief review of ethical issues in developmental research, situated within the emerging field of neuroethics, highlights the increasingly interdisciplinary nature of…

  19. Functional neuroimaging of human vocalizations and affective speech.

    PubMed

    Frühholz, Sascha; Sander, David; Grandjean, Didier

    2014-12-01

    Neuroimaging studies have verified the important integrative role of the basal ganglia during affective vocalizations. They, however, also point to additional regions supporting vocal monitoring, auditory-motor feedback processing, and online adjustments of vocal motor responses. For the case of affective vocalizations, we suggest partly extending the model to fully consider the link between primate-general and human-specific neural components.

  20. A Developmental Neuroimaging Investigation of the Change Paradigm

    ERIC Educational Resources Information Center

    Thomas, Laura A.; Hall, Julie M.; Skup, Martha; Jenkins, Sarah E.; Pine, Daniel S.; Leibenluft, Ellen

    2011-01-01

    This neuroimaging study examines the development of cognitive flexibility using the Change task in a sample of youths and adults. The Change task requires subjects to inhibit a prepotent response and substitute an alternative response, and the task incorporates an algorithm that adjusts task difficulty in response to subject performance. Data from…

  1. Memory Systems, Processing Modes, and Components: Functional Neuroimaging Evidence.

    PubMed

    Cabeza, Roberto; Moscovitch, Morris

    2013-01-01

    In the 1980s and 1990s, there was a major theoretical debate in the memory domain regarding the multiple memory systems and processing modes frameworks. The components of processing framework argued for a middle ground: Instead of neatly divided memory systems or processing modes, this framework proposed the existence of numerous processing components that are recruited in different combinations by memory tasks and yield complex patterns of associations and dissociations. Because behavioral evidence was not sufficient to decide among these three frameworks, the debate was largely abandoned. However, functional neuroimaging evidence accumulated during the last two decades resolves the stalemate, because this evidence is more consistent with the components framework than with the other two frameworks. For example, functional neuroimaging evidence shows that brain regions attributed to one memory system can contribute to tasks associated with other memory systems and that brain regions attributed to the same processing mode (perceptual or conceptual) can be dissociated from each other. Functional neuroimaging evidence suggests that memory processes are supported by transient interactions between a few regions called process-specific alliances. These conceptual developments are an example of how functional neuroimaging can contribute to theoretical debates in cognitive psychology.

  2. Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls

    PubMed Central

    Falcone, Mary; Smith, Ryan M; Chenoweth, Meghan J; Kumar Bhattacharjee, Abesh; Kelsoe, John R; Tyndale, Rachel F; Lerman, Caryn

    2013-01-01

    The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment. PMID:23793356

  3. Neuroimaging of the Periaqueductal Gray: State of the Field

    PubMed Central

    Linnman, Clas; Moulton, Eric A.; Barmettler, Gabi; Becerra, Lino; Borsook, David

    2011-01-01

    This review and meta-analysis aims at summarizing and integrating the human neuroimaging studies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimaging studies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region. PMID:22197740

  4. Uncovering the etiology of conversion disorder: insights from functional neuroimaging

    PubMed Central

    Ejareh dar, Maryam; Kanaan, Richard AA

    2016-01-01

    Conversion disorder (CD) is a syndrome of neurological symptoms arising without organic cause, arguably in response to emotional stress, but the exact neural substrates of these symptoms and the underlying mechanisms remain poorly understood with the hunt for a biological basis afoot for centuries. In the past 15 years, novel insights have been gained with the advent of functional neuroimaging studies in patients suffering from CDs in both motor and nonmotor domains. This review summarizes recent functional neuroimaging studies including functional magnetic resonance imaging (fMRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET) to see whether they bring us closer to understanding the etiology of CD. Convergent functional neuroimaging findings suggest alterations in brain circuits that could point to different mechanisms for manifesting functional neurological symptoms, in contrast with feigning or healthy controls. Abnormalities in emotion processing and in emotion-motor processing suggest a diathesis, while differential reactions to certain stressors implicate a specific response to trauma. No comprehensive theory emerges from these clues, and all results remain preliminary, but functional neuroimaging has at least given grounds for hope that a model for CD may soon be found. PMID:26834476

  5. Uncovering the etiology of conversion disorder: insights from functional neuroimaging.

    PubMed

    Ejareh Dar, Maryam; Kanaan, Richard Aa

    2016-01-01

    Conversion disorder (CD) is a syndrome of neurological symptoms arising without organic cause, arguably in response to emotional stress, but the exact neural substrates of these symptoms and the underlying mechanisms remain poorly understood with the hunt for a biological basis afoot for centuries. In the past 15 years, novel insights have been gained with the advent of functional neuroimaging studies in patients suffering from CDs in both motor and nonmotor domains. This review summarizes recent functional neuroimaging studies including functional magnetic resonance imaging (fMRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET) to see whether they bring us closer to understanding the etiology of CD. Convergent functional neuroimaging findings suggest alterations in brain circuits that could point to different mechanisms for manifesting functional neurological symptoms, in contrast with feigning or healthy controls. Abnormalities in emotion processing and in emotion-motor processing suggest a diathesis, while differential reactions to certain stressors implicate a specific response to trauma. No comprehensive theory emerges from these clues, and all results remain preliminary, but functional neuroimaging has at least given grounds for hope that a model for CD may soon be found.

  6. 8th HUPO World Congress: the Human Disease Glycomics/Proteomics Initiative (HGPI) Session 26 September 2009, Toronto, Canada.

    PubMed

    Narimatsu, Hisashi

    2010-05-01

    The Human Disease Glycomics/Proteomics Initiative (HGPI) Session at the HUPO World Congress was held in Toronto on 26 September 2009. In this report, we summarize the presentation of the HGPI workshop as follows: (i) The results of the past HGPI pilot studies (first and second) in which we analyzed N- and O-linked glycans using standard glycoproteins (i.e. first: N-linked glycan analysis of transferrin and IgG; second: O-linked glycan analysis of IgA). (ii) The recent progresses of the current HGPI third pilot study. The third analytical pilot study is in progress to perform the two tasks, which are glycan structural analysis and identification of proteins which carry specific carbohydrate antigen (Lewis X antigen) using cancer cells (i.e. L428, U937, and SK-N-SH), under the theme of "Glyco-Biomarker Discovery". Finally, recently advanced glycomic and glycoproteomic analyses were also reported.

  7. Genetic Variation of North American Triatomines (Insecta: Hemiptera: Reduviidae): Initial Divergence between Species and Populations of Chagas Disease Vector

    PubMed Central

    Espinoza, Bertha; Martínez-Ibarra, Jose Alejandro; Villalobos, Guiehdani; De La Torre, Patricia; Laclette, Juan Pedro; Martínez-Hernández, Fernando

    2013-01-01

    The triatomines vectors of Trypanosoma cruzi are principal factors in acquiring Chagas disease. For this reason, increased knowledge of domestic transmission of T. cruzi and control of its insect vectors is necessary. To contribute to genetic knowledge of North America Triatominae species, we studied genetic variations and conducted phylogenetic analysis of different triatomines species of epidemiologic importance. Our analysis showed high genetic variations between different geographic populations of Triatoma mexicana, Meccus longipennis, M. mazzottii, M. picturatus, and T. dimidiata species, suggested initial divergence, hybridation, or classifications problems. In contrast, T. gerstaeckeri, T. bolivari, and M. pallidipennis populations showed few genetics variations. Analysis using cytochrome B and internal transcribed spacer 2 gene sequences indicated that T. bolivari is closely related to the Rubrofasciata complex and not to T. dimidiata. Triatoma brailovskyi and T. gerstaeckeri showed a close relationship with Dimidiata and Phyllosoma complexes. PMID:23249692

  8. Neuroimaging: A Window to the Neurological Foundations of Learning and Behavior in Children.

    ERIC Educational Resources Information Center

    Lyon, G. Reid, Ed.; Rumsey, Judith M., Ed.

    This book presents 11 papers on the use of neuroimaging technology in brain-related disorders. The text contains full-color neuroimaging scans and provides both theoretical and methodological explanations of the various neuroimaging techniques and their application to developmental disorders in children. The papers are grouped into three sections,…

  9. Nonhuman primate positron emission tomography neuroimaging in drug abuse research.

    PubMed

    Howell, Leonard Lee; Murnane, Kevin Sean

    2011-05-01

    Positron emission tomography (PET) neuroimaging in nonhuman primates has led to significant advances in our current understanding of the neurobiology and treatment of stimulant addiction in humans. PET neuroimaging has defined the in vivo biodistribution and pharmacokinetics of abused drugs and related these findings to the time course of behavioral effects associated with their addictive properties. With novel radiotracers and enhanced resolution, PET neuroimaging techniques have also characterized in vivo drug interactions with specific protein targets in the brain, including neurotransmitter receptors and transporters. In vivo determinations of cerebral blood flow and metabolism have localized brain circuits implicated in the effects of abused drugs and drug-associated stimuli. Moreover, determinations of the predisposing factors to chronic drug use and long-term neurobiological consequences of chronic drug use, such as potential neurotoxicity, have led to novel insights regarding the pathology and treatment of drug addiction. However, similar approaches clearly need to be extended to drug classes other than stimulants. Although dopaminergic systems have been extensively studied, other neurotransmitter systems known to play a critical role in the pharmacological effects of abused drugs have been largely ignored in nonhuman primate PET neuroimaging. Finally, the study of brain activation with PET neuroimaging has been replaced in humans mostly by functional magnetic resonance imaging (fMRI). There has been some success in implementing pharmacological fMRI in awake nonhuman primates. Nevertheless, the unique versatility of PET imaging will continue to complement the systems-level strengths of fMRI, especially in the context of nonhuman primate drug abuse research.

  10. COINS: An Innovative Informatics and Neuroimaging Tool Suite Built for Large Heterogeneous Datasets

    PubMed Central

    Scott, Adam; Courtney, Will; Wood, Dylan; de la Garza, Raul; Lane, Susan; King, Margaret; Wang, Runtang; Roberts, Jody; Turner, Jessica A.; Calhoun, Vince D.

    2011-01-01

    The availability of well-characterized neuroimaging data with large numbers of subjects, especially for clinical populations, is critical to advancing our understanding of the healthy and diseased brain. Such data enables questions to be answered in a much more generalizable manner and also has the potential to yield solutions derived from novel methods that were conceived after the original studies’ implementation. Though there is currently growing interest in data sharing, the neuroimaging community has been struggling for years with how to best encourage sharing data across brain imaging studies. With the advent of studies that are much more consistent across sites (e.g., resting functional magnetic resonance imaging, diffusion tensor imaging, and structural imaging) the potential of pooling data across studies continues to gain momentum. At the mind research network, we have developed the collaborative informatics and neuroimaging suite (COINS; http://coins.mrn.org) to provide researchers with an information system based on an open-source model that includes web-based tools to manage studies, subjects, imaging, clinical data, and other assessments. The system currently hosts data from nine institutions, over 300 studies, over 14,000 subjects, and over 19,000 MRI, MEG, and EEG scan sessions in addition to more than 180,000 clinical assessments. In this paper we provide a description of COINS with comparison to a valuable and popular system known as XNAT. Although there are many similarities between COINS and other electronic data management systems, the differences that may concern researchers in the context of multi-site, multi-organizational data sharing environments with intuitive ease of use and PHI security are emphasized as important attributes. PMID:22275896

  11. Lighten up: Specific postural instructions affect axial rigidity and step initiation in patients with Parkinson’s disease

    PubMed Central

    Cohen, Rajal G.; Gurfinkel, Victor S.; Kwak, Elizabeth; Warden, Amelia C.; Horak, Fay B.

    2015-01-01

    Background Parkinson’s disease (PD) is associated with stooped postural alignment, increased postural sway, and reduced mobility. The Alexander Technique (AT) is a mindfulness-based approach to improving posture and mobility by reducing muscular interference while maintaining upward intentions. Evidence suggests that AT can reduce disability associated with PD, but a mechanism for this effect has not yet been established. Objective We investigated whether AT-based instructions reduce axial rigidity and increase upright postural alignment, and whether these instructions have different effects on postural alignment, axial rigidity, postural sway, and mobility than effort-based instructions regarding posture. Method Twenty subjects with PD practiced two sets of instructions and then attempted to implement both approaches (as well as a relaxed control condition) during quiet standing and step initiation. The ‘Lighten Up’ instructions relied on AT principles of reducing excess tension while encouraging length. The ‘Pull Up’ instructions relied on popular concepts of effortful posture correction. We measured kinematics, resistance to axial rotation, and ground reaction forces. Results Both sets of experimental instructions led to increases in upright postural alignment relative to the control condition. Only the Lighten Up instructions led to reduced postural sway, reduced axial postural tone, greater modifiability of tone, and a smoother center of pressure trajectory during step initiation, possibly indicating greater movement efficiency. Conclusion Mindful movement approaches such as AT may benefit balance and mobility in subjects with PD by acutely facilitating increased upright postural alignment while decreasing rigidity. PMID:25665828

  12. The Influence of a Cognitive Task on the Postural Phase of Gait Initiation in Parkinson's Disease: An Electromyographic Based Analysis.

    PubMed

    Fernandes, Ângela; Sousa, Andreia S P; Rocha, Nuno; Tavares, João Manuel R S

    2016-08-19

    The aim of this study was to compare postural control strategies during gait initiation in single- and dual-task conditions in individuals in early stages of Parkinson´s Disease (PD). The activation timing of tibialis anterior occurred significantly later in the individuals with PD than in the controls (p=0.05), and a significant interaction between the groups, conditions and limbs was found (p=0.027). Differences between the single- and dual-task conditions were observed for the activation timing of the tibialis anterior (p=0.042) and for the magnitude of soleus (p=0.007), with lower values for the dual-task condition. Furthermore, not all the individuals followed the previously reported pattern of soleus inhibition followed by tibialis anterior activation. The duration of the mediolateral displacement of the centre of pressure was longer in the individuals with PD than in the controls (p=0.019). The anticipatory postural adjustments during gait initiation are impaired in PD and are expressed by an activation failure of tibialis anterior in both single- and dual-task conditions. Hence, it is important that during rehabilitation, intervention should concentrate on the TA.

  13. Relationship between cardiac calcification and left ventricular hypertrophy in patients with chronic kidney disease at hemodialysis initiation.

    PubMed

    Kitamura, Ken; Fujii, Hideki; Nakai, Kentaro; Kono, Keiji; Goto, Shunsuke; Nishii, Tatsuya; Kono, Atsushi; Nishi, Shinichi

    2017-03-21

    Coronary artery calcification (CAC), cardiac valve calcification (CVC) and left ventricular hypertrophy (LVH) are frequently observed in chronic kidney disease (CKD) patients. These abnormalities significantly affect morbidity and mortality. The aim of this study was to investigate the relationship between CAC, CVC and LVH in CKD patients. This study included 96 patients who were hospitalized and initiated hemodialysis between December 2011 and July 2014 at our five institutions. Multi-detector computed tomography for the quantification of CAC using the Agatston score and transthoracic echocardiography for assessing CVC and LVH were performed for all patients included in the study. We semi-quantitatively evaluated the severity of CVC as a valvular calcification score. We also assessed the presence of LVH in patients with CAC and/or CVC. Among the 96 patients, the prevalence of CAC was 81.3% and CVC was 65.0%. The severity of CAC was closely and significantly associated with that of CVC. The percentage of patients with LVH was the greatest in those with both severe CAC and CVC. CAC was significantly more severe in patients with concentric hypertrophy compared to those with normal geometry. At the initiation of hemodialysis, most CKD patients had CAC, CVC and LVH. In addition, cardiac calcification was significantly associated with LVH in these patients.

  14. Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson's disease: a meta-analysis.

    PubMed

    Xie, Cheng-long; Zhang, Yun-Yun; Wang, Xiao-Dan; Chen, Jie; Chen, Yi-He; Pa, Jia-Lin; Lin, Shi-Yi; Lin, Hua-Zhen; Wang, Wen-Wen

    2015-08-01

    To assess the long-term use of L-dopa alone vs L-dopa-sparing therapy, as initial treatment, provides the most efficient long-term control of symptoms and best quality of life for people with early Parkinson's disease (PD). PubMed; Google scholar; Cochrane Central Register of Controlled Trials and the Web of Science were searched for randomised, placebo-controlled trials (RCTs) on L-dopa alone and L-dopa sparing as initial treatment in early PD patients. We used a random effects model rather than a fixed effects model because of this takes into account heterogeneity between multi-studies. Eleven RCTs were included. The results showed that L-dopa alone could evidently improve the UPDRS part I (p = 0.005), part II (p < 0.0001), part III (p < 0.0001) and UPDRS total score (p = 0.004) compared with L-dopa-sparing therapy in PD patients. Meanwhile, a reduced risk of dyskinesia (p < 0.0001, RR = 1.88, 95 % CI 1. 37-2.59) and wearing-off phenomenon (p < 0.00001, RR = 1.36, 95 % CI 1. 20-1.55) in patients treated initially with L-dopa-sparing therapy compared to L-dopa has been consistently reported. What is more, we found more patients on aL-dopa-sparing therapy were more than triple as likely to discontinue treatment prematurely due to adverse events than L-dopa treatment patients (43.7 vs 15.8 %). L-Dopa alone is the most effective medication available for treating the motor symptoms of PD patients, despite the greater incidence of involuntary movements. Meanwhile, more patients on dopamine agonists or MAOBI were more likely to discontinue treatment prematurely than L-dopa alone treatment patients within the long follow-up period.

  15. Spinocerebellar ataxia type 2 (SCA2): identification of early brain degeneration in one monozygous twin in the initial disease stage.

    PubMed

    Hoche, Franziska; Balikó, Laszlo; den Dunnen, Wilfred; Steinecker, Katalin; Bartos, Laszlo; Sáfrány, Eniko; Auburger, Georg; Deller, Thomas; Korf, Horst-Werner; Klockgether, Thomas; Rüb, Udo; Melegh, Bela

    2011-06-01

    Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG repeat or polyglutamine diseases. Recent morphological studies characterized the pathoanatomical features in heterozygous SCA2 patients and revealed severe neuronal loss in a large variety of cerebellar and extra-cerebellar brain sites. In the present study, we examined the brain pathoanatomy of a monozygous twin of a large Hungarian SCA2 family with pathologically extended CAG repeats in both SCA2 alleles. This unique patient was in the initial clinical stage of SCA2 and died almost 3 years after SCA2 onset. Upon pathoanatomical investigation, we observed loss of giant Betz pyramidal cells in the primary motor cortex, degeneration of sensory thalamic nuclei, the Purkinje cell layer, and deep cerebellar nuclei, as well as select brainstem nuclei (i.e., substantia nigra, oculomotor nucleus, reticulotegmental nucleus of the pons, facial, lateral vestibular, and raphe interpositus nuclei, inferior olive). All of these degenerated brain gray matter structures are known as consistent targets of the underlying pathological process in heterozygous SCA2 patients. Since they were already involved in our patient within 3 years after disease onset, we think that we were for the first time able to identify the early brain targets of the pathological process of SCA2.

  16. Treatment Patterns and Outcome Following Initial Relapse or Refractory Disease in Patients with Systemic Light Chain Amyloidosis.

    PubMed

    Tandon, Nidhi; Sidana, Surbhi; Gertz, Morie A; Dispenzieri, Angela; Lacy, Martha Q; Buadi, Francis K; Dingli, David; Fonder, Amie L; Hobbs, Miriam A; Hayman, Suzanne R; Gonsalves, Wilson I; Hwa, Yi Lisa; Kapoor, Prashant; Kyle, Robert A; Leung, Nelson; Go, Ronald S; Lust, John A; Russell, Stephen J; Zeldenrust, Steven R; Rajkumar, S Vincent; Kumar, Shaji K

    2017-03-17

    We analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1-93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22m vs 32.3m; p= 0.01) as compared to different therapy; but did not have any impact OS (30.8m vs 51.1m; p = 0.5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS. This article is protected by copyright. All rights reserved.

  17. Preliminary report of improved sleep quality in patients with dry eye disease after initiation of topical therapy

    PubMed Central

    Ayaki, Masahiko; Toda, Ikuko; Tachi, Naoko; Negishi, Kazuno; Tsubota, Kazuo

    2016-01-01

    Purpose Dry eye disease (DED) is potentially associated with sleep and mood disorders. This study evaluated sleep quality in patients with DED using a questionnaire-based survey before and after topical eyedrop treatment. The effectiveness of sleep and ophthalmic services in assisting with sleep problems in patients with eye disease was also assessed. Methods Seventy-one consecutive patients with DED visiting eight general eye clinics in various locations answered a questionnaire containing the Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. Photophobia and chronotype (morningness/eveningness) were also evaluated with two representative questions from established questionnaires (National Eye Institute Visual Function Questionnaire-25 and Morningness/Eveningness questionnaire). Follow-up evaluation was conducted by interview or mail 3–10 months after the initial evaluation. A sleep service was established in two eye clinics to identify possible ocular diseases related to sleep and mood disorders; it comprised a questionnaire, sleep diary, actigram, medical interviews, visual field testing, retinal ganglion cell layer thickness measurement, and DED examination. Results Patients with newly diagnosed DED exhibited a greater improvement in sleep after DED treatment compared with patients with established DED. Improvement in Pittsburgh Sleep Quality Index was significant (P<0.05) and strongly correlated with improvement in Hospital Anxiety and Depression Scale (P<0.05) for new patients, but not for patients with established DED. Ten eye clinic patients visited the sleep service and nine of them had DED. They were successfully treated with eyedrops and sleep services, which included blue-light-shield eyewear and wearable blue-light therapy lamps according to their problem. Conclusion Sleep quality improved in patients with DED after topical treatment with or without the sleep service. Psychiatric treatment focusing on sleep disorders could be

  18. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment

    PubMed Central

    Kaler, Stephen G.

    2014-01-01

    Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6 to 8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation, and presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n=35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation. PMID:25281031

  19. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.

    PubMed

    Kaler, Stephen G

    2014-10-01

    Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation and potential presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n=35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation.

  20. A hybrid manifold learning algorithm for the diagnosis and prognostication of Alzheimer's disease.

    PubMed

    Dai, Peng; Gwadry-Sridhar, Femida; Bauer, Michael; Borrie, Michael

    The diagnosis of Alzheimer's disease (AD) requires a variety of medical tests, which leads to huge amounts of multivariate heterogeneous data. Such data are difficult to compare, visualize, and analyze due to the heterogeneous nature of medical tests. We present a hybrid manifold learning framework, which embeds the feature vectors in a subspace preserving the underlying pairwise similarity structure, i.e. similar/dissimilar pairs. Evaluation tests are carried out using the neuroimaging and biological data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) in a three-class (normal, mild cognitive impairment, and AD) classification task using support vector machine (SVM). Furthermore, we make extensive comparison with standard manifold learning algorithms, such as Principal Component Analysis (PCA), Principal Component Analysis (PCA), Multidimensional Scaling (MDS), and isometric feature mapping (Isomap). Experimental results show that our proposed algorithm yields an overall accuracy of 85.33% in the three-class task.

  1. Economic evaluation of participation in a voluntary Johne's disease prevention and control program from a farmer's perspective--The Alberta Johne's Disease Initiative.

    PubMed

    Wolf, R; Clement, F; Barkema, H W; Orsel, K

    2014-05-01

    The Alberta Johne's Disease Initiative (AJDI) is a Johne's disease (JD) control program with the goal of reducing the spread of Mycobacterium avium ssp. paratuberculosis (MAP) through implementation of best management practices. The objective was to estimate the economic benefit of participation in the AJDI. A decision tree was constructed in which disease prevalence, test characteristics, and probabilities for implementation of best management practices suggested by herd veterinarians were implemented. Analysis was performed using a Markov analysis, and input data were assigned using estimates from the AJDI and published data. A cost-effectiveness analysis was performed and the net benefit of participation (from the perspective of a dairy farmer) in the AJDI compared with no participation was calculated. A series of 1-way sensitivity analyses were used to control for uncertainty. Farms participating in the AJDI were estimated to have a net benefit of Can$74 per cow over the course of 10 yr. If project costs were covered by the participating farm, the net benefit was Can$27. In addition to the effects on MAP infection, a reduction in calf diarrhea was modeled for farms that improved their calf management through the use of pasteurizers. In that case, the additional costs outweighed additional revenues compared with the baseline analysis, resulting in a reduced net benefit of Can$19. Participation would not be cost effective if cows in early stages of MAP infection did not have decreased production and if prevalence of MAP infection did not increase on farms with poor management. A limitation of the study, despite high uncertainty in some input parameters, was the lack of knowledge regarding changes in prevalence on farms with various management strategies. In conclusion, participation in the AJDI was cost effective for the average Alberta dairy farm.

  2. National Studies as a Component of the World Health Organization Initiative to Estimate the Global and Regional Burden of Foodborne Disease

    PubMed Central

    Lake, Robin J.; Devleesschauwer, Brecht; Nasinyama, George; Havelaar, Arie H.; Kuchenmüller, Tanja; Haagsma, Juanita A.; Jensen, Helen H.; Jessani, Nasreen; Maertens de Noordhout, Charline; Angulo, Frederick J.; Ehiri, John E.; Molla, Lindita; Agaba, Friday; Aungkulanon, Suchunya; Kumagai, Yuko; Speybroeck, Niko

    2015-01-01

    Background The World Health Organization (WHO) initiative to estimate the global burden of foodborne diseases established the Foodborne Diseases Burden Epidemiology Reference Group (FERG) in 2007. In addition to global and regional estimates, the initiative sought to promote actions at a national level. This involved capacity building through national foodborne disease burden studies, and encouragement of the use of burden information in setting evidence-informed policies. To address these objectives a FERG Country Studies Task Force was established and has developed a suite of tools and resources to facilitate national burden of foodborne disease studies. This paper describes the process and lessons learned during the conduct of pilot country studies under the WHO FERG initiative. Findings Pilot country studies were initiated in Albania, Japan and Thailand in 2011 and in Uganda in 2012. A brief description of each study is provided. The major scientific issue is a lack of data, particularly in relation to disease etiology, and attribution of disease burden to foodborne transmission. Situation analysis, knowledge translation, and risk communication to achieve evidence-informed policies require specialist expertise and resources. Conclusions The FERG global and regional burden estimates will greatly enhance the ability of individual countries to fill data gaps and generate national estimates to support efforts to reduce the burden of foodborne disease. PMID:26633010

  3. Sharing privacy-sensitive access to neuroimaging and genetics data: a review and preliminary validation

    PubMed Central

    Sarwate, Anand D.; Plis, Sergey M.; Turner, Jessica A.; Arbabshirani, Mohammad R.; Calhoun, Vince D.

    2014-01-01

    The growth of data sharing initiatives for neuroimaging and genomics represents an exciting opportunity to confront the “small N” problem that plagues contemporary neuroimaging studies while further understanding the role genetic markers play in the function of the brain. When it is possible, open data sharing provides the most benefits. However, some data cannot be shared at all due to privacy concerns and/or risk of re-identification. Sharing other data sets is hampered by the proliferation of complex data use agreements (DUAs) which preclude truly automated data mining. These DUAs arise because of concerns about the privacy and confidentiality for subjects; though many do permit direct access to data, they often require a cumbersome approval process that can take months. An alternative approach is to only share data derivatives such as statistical summaries—the challenges here are to reformulate computational methods to quantify the privacy risks associated with sharing the results of those computations. For example, a derived map of gray matter is often as identifiable as a fingerprint. Thus alternative approaches to accessing data are needed. This paper reviews the relevant literature on differential privacy, a framework for measuring and tracking privacy loss in these settings, and demonstrates the feasibility of using this framework to calculate statistics on data distributed at many sites while still providing privacy. PMID:24778614

  4. Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging

    PubMed Central

    Eugene, Andy R.; Masiak, Jolanta

    2016-01-01

    Background Selective Mutism is described as the inability to verbally express oneself in anxiety provoking social situations and may result in awkward social interactions in school-aged children. In this case-report we present the baseline electrophysiological neuroimaging results and after treatment with Sertraline for 6-weeks. Methods A 20-channel EEG event-related potential recording was acquired during an internal voice task at baseline prior to the initiation of 50mg of Sertraline and then repeated 6-weeks after treatment with Sertraline. EEG signals were processed for movement, eye-blink, and muscle artifacts and ERP signal averaging was completed. ERPs were analyzed using Standard Low Resolution Brain Electromagnetic Tomography (sLORETA). Results At baseline, Sertraline increased the neuronal activation in the middle temporal gyrus and the anterior cingulate gyrus from baseline in the patient following 6-weeks of treatment. Conclusion Our findings suggest that electrophysiological neuroimaging may provide a creative approach for personalizing medicine by providing insight to the pharmacodynamics of antidepressants. PMID:27468379

  5. Clinical and neuroimaging biomarkers of amyloid-negative logopenic primary progressive aphasia

    PubMed Central

    Whitwell, Jennifer L.; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Schwarz, Christopher G.; Reid, Robert; Baker, Matthew C.; Perkerson, Ralph B.; Lowe, Val J.; Rademakers, Rosa; Jack, Clifford R.; Josephs, Keith A.

    2015-01-01

    Logopenic primary progressive aphasia (lvPPA) is a progressive language disorder characterized by anomia, difficulty repeating complex sentences, and phonological errors. The majority, although not all, lvPPA patients have underlying Alzheimer’s disease. We aimed to determine whether clinical or neuroimaging features differ according to the deposition of Aβ on Pittsburgh-compound B PET in lvPPA. Clinical features, patterns of atrophy on MRI, hypometabolism on FDG-PET, and white matter tract degeneration were compared between six PiB-negative and 20 PiB-positive lvPPA patients. PiB-negative patients showed more asymmetric left-sided patterns of atrophy, hypometabolism and white matter tract degeneration, with greater left anteromedial temporal and medial prefrontal involvement, than PiB-positive patients. PiB-positive patients showed greater involvement of right temporoparietal and frontal lobes. There was very little evidence for clinical differences between the groups. Strikingly asymmetric neuroimaging findings with relatively preserved right hemisphere may provide clues that AD pathology is absent in lvPPA. PMID:25658633

  6. Interpreting support vector machine models for multivariate group wise analysis in neuroimaging.

    PubMed

    Gaonkar, Bilwaj; T Shinohara, Russell; Davatzikos, Christos

    2015-08-01

    Machine learning based classification algorithms like support vector machines (SVMs) have shown great promise for turning a high dimensional neuroimaging data into clinically useful decision criteria. However, tracing imaging based patterns that contribute significantly to classifier decisions remains an open problem. This is an issue of critical importance in imaging studies seeking to determine which anatomical or physiological imaging features contribute to the classifier's decision, thereby allowing users to critically evaluate the findings of such machine learning methods and to understand disease mechanisms. The majority of published work addresses the question of statistical inference for support vector classification using permutation tests based on SVM weight vectors. Such permutation testing ignores the SVM margin, which is critical in SVM theory. In this work we emphasize the use of a statistic that explicitly accounts for the SVM margin and show that the null distributions associated with this statistic are asymptotically normal. Further, our experiments show that this statistic is a lot less conservative as compared to weight based permutation tests and yet specific enough to tease out multivariate patterns in the data. Thus, we can better understand the multivariate patterns that the SVM uses for neuroimaging based classification.

  7. A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury

    PubMed Central

    Amyot, Franck; Arciniegas, David B.; Brazaitis, Michael P.; Curley, Kenneth C.; Diaz-Arrastia, Ramon; Gandjbakhche, Amir; Herscovitch, Peter; Hinds, Sidney R.; Manley, Geoffrey T.; Razumovsky, Alexander; Riley, Jason; Salzer, Wanda; Shih, Robert; Smirniotopoulos, James G.; Stocker, Derek

    2015-01-01

    Abstract The incidence of traumatic brain injury (TBI) in the United States was 3.5 million cases in 2009, according to the Centers for Disease Control and Prevention. It is a contributing factor in 30.5% of injury-related deaths among civilians. Additionally, since 2000, more than 260,000 service members were diagnosed with TBI, with the vast majority classified as mild or concussive (76%). The objective assessment of TBI via imaging is a critical research gap, both in the military and civilian communities. In 2011, the Department of Defense (DoD) prepared a congressional report summarizing the effectiveness of seven neuroimaging modalities (computed tomography [CT], magnetic resonance imaging [MRI], transcranial Doppler [TCD], positron emission tomography, single photon emission computed tomography, electrophysiologic techniques [magnetoencephalography and electroencephalography], and functional near-infrared spectroscopy) to assess the spectrum of TBI from concussion to coma. For this report, neuroimaging experts identified the most relevant peer-reviewed publications and assessed the quality of the literature for each of these imaging technique in the clinical and research settings. Although CT, MRI, and TCD were determined to be the most useful modalities in the clinical setting, no single imaging modality proved sufficient for all patients due to the heterogeneity of TBI. All imaging modalities reviewed demonstrated the potential to emerge as part of future clinical care. This paper describes and updates the results of the DoD report and also expands on the use of angiography in patients with TBI. PMID:26176603

  8. The Role of Functional Neuroimaging in Pre-Surgical Epilepsy Evaluation

    PubMed Central

    Pittau, Francesca; Grouiller, Frédéric; Spinelli, Laurent; Seeck, Margitta; Michel, Christoph M.; Vulliemoz, Serge

    2014-01-01

    The prevalence of epilepsy is about 1% and one-third of cases do not respond to medical treatment. In an eligible subset of patients with drug-resistant epilepsy, surgical resection of the epileptogenic zone is the only treatment that can possibly cure the disease. Non-invasive techniques provide information for the localization of the epileptic focus in the majority of cases, whereas in others invasive procedures are required. In the last years, non-invasive neuroimaging techniques, such as simultaneous recording of functional magnetic resonance imaging and electroencephalogram (EEG-fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), electric and magnetic source imaging (MSI, ESI), spectroscopy (MRS), have proved their usefulness in defining the epileptic focus. The combination of these functional techniques can yield complementary information and their concordance is crucial for guiding clinical decision, namely the planning of invasive EEG recordings or respective surgery. The aim of this review is to present these non-invasive neuroimaging techniques, their potential combination, and their role in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. PMID:24715886

  9. Interpreting support vector machine models for multivariate group wise analysis in neuroimaging

    PubMed Central

    Gaonkar, Bilwaj; Shinohara, Russell T; Davatzikos, Christos

    2015-01-01

    Machine learning based classification algorithms like support vector machines (SVMs) have shown great promise for turning a high dimensional neuroimaging data into clinically useful decision criteria. However, tracing imaging based patterns that contribute significantly to classifier decisions remains an open problem. This is an issue of critical importance in imaging studies seeking to determine which anatomical or physiological imaging features contribute to the classifier’s decision, thereby allowing users to critically evaluate the findings of such machine learning methods and to understand disease mechanisms. The majority of published work addresses the question of statistical inference for support vector classification using permutation tests based on SVM weight vectors. Such permutation testing ignores the SVM margin, which is critical in SVM theory. In this work we emphasize the use of a statistic that explicitly accounts for the SVM margin and show that the null distributions associated with this statistic are asymptotically normal. Further, our experiments show that this statistic is a lot less conservative as compared to weight based permutation tests and yet specific enough to tease out multivariate patterns in the data. Thus, we can better understand the multivariate patterns that the SVM uses for neuroimaging based classification. PMID:26210913

  10. Neuroimaging features of xeroderma pigmentosum group A.

    PubMed

    Ueda, Takehiro; Kanda, Fumio; Aoyama, Nobukazu; Fujii, Masahiko; Nishigori, Chikako; Toda, Tatsushi

    2012-01-01

    Xeroderma pigmentosum group A (XPA) is a hereditary dermatological disease in which hypersensitivity to ultraviolet radiation and various neurological symptoms are observed. In this study, to evaluate the degeneration occurring in the brain of XPA patients, neurological examinations by an established neurologist and 3-Tesla magnetic resonance imaging (MRI) were performed in 10 Japanese XPA patients. MRI studies included diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) in addition to conventional sequences. Neurological examinations revealed various deteriorations in the both central and peripheral nervous systems in all subjects. MRI studies demonstrated age-dependent decline in multimodalities. Severe brain atrophy in conventional sequences, decreased fractional anisotropy (FA) value in DTI, and reduced NAA/Cre ratio in MRS were observed in the adult patients. Multimodal MRI studies unmask the neurological deterioration in XPA patients.

  11. A telemedicine instrument for remote evaluation of tremor: design and initial applications in fatigue and patients with Parkinson's Disease

    PubMed Central

    2011-01-01

    Introduction A novel system that combines a compact mobile instrument and Internet communications is presented in this paper for remote evaluation of tremors. The system presents a high potential application in Parkinson's disease and connects to the Internet through a TCP/IP protocol. Tremor transduction is carried out by accelerometers, and the data processing, presentation and storage were obtained by a virtual instrument. The system supplies the peak frequency (fp), the amplitude (Afp) and power in this frequency (Pfp), the total power (Ptot), and the power in low (1-4 Hz) and high (4-7 Hz) frequencies (Plf and Phf, respectively). Methods The ability of the proposed system to detect abnormal tremors was initially demonstrated by a fatigue study in normal subjects. In close agreement with physiological fundamentals, the presence of fatigue increased fp, Afp, Pfp and Pt (p < 0.05), while the removal of fatigue reduced all the mentioned parameters (p < 0.05). The system was also evaluated in a preliminary in vivo test in parkinsonian patients. Afp, Pfp, Ptot, Plf and Phf were the most accurate parameters in the detection of the adverse effects of this disease (Se = 100%, Sp = 100%), followed by fp (Se = 100%, Sp = 80%). Tests for Internet transmission that realistically simulated clinical conditions revealed adequate acquisition and analysis of tremor signals and also revealed that the user could adequately receive medical recommendations. Conclusions The proposed system can be used in a wide spectrum of telemedicine scenarios, enabling the home evaluation of tremor occurrence under specific medical treatments and contributing to reduce the costs of the assistance offered to these patients. PMID:21306628

  12. Pain perception and hypnosis: findings from recent functional neuroimaging studies.

    PubMed

    Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

    2015-01-01

    Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

  13. Genetic imaging consortium for addiction medicine: From neuroimaging to genes.

    PubMed

    Mackey, Scott; Kan, Kees-Jan; Chaarani, Bader; Alia-Klein, Nelly; Batalla, Albert; Brooks, Samantha; Cousijn, Janna; Dagher, Alain; de Ruiter, Michiel; Desrivieres, Sylvane; Feldstein Ewing, Sarah W; Goldstein, Rita Z; Goudriaan, Anna E; Heitzeg, Mary M; Hutchison, Kent; Li, Chiang-Shan R; London, Edythe D; Lorenzetti, Valentina; Luijten, Maartje; Martin-Santos, Rocio; Morales, Angelica M; Paulus, Martin P; Paus, Tomas; Pearlson, Godfrey; Schluter, Renée; Momenan, Reza; Schmaal, Lianne; Schumann, Gunter; Sinha, Rajita; Sjoerds, Zsuzsika; Stein, Dan J; Stein, Elliot A; Solowij, Nadia; Tapert, Susan; Uhlmann, Anne; Veltman, Dick; van Holst, Ruth; Walter, Henrik; Wright, Margaret J; Yucel, Murat; Yurgelun-Todd, Deborah; Hibar, Derrek P; Jahanshad, Neda; Thompson, Paul M; Glahn, David C; Garavan, Hugh; Conrod, Patricia

    2016-01-01

    Since the sample size of a typical neuroimaging study lacks sufficient statistical power to explore unknown genomic associations with brain phenotypes, several international genetic imaging consortia have been organized in recent years to pool data across sites. The challenges and achievements of these consortia are considered here with the goal of leveraging these resources to study addiction. The authors of this review have joined together to form an Addiction working group within the framework of the ENIGMA project, a meta-analytic approach to multisite genetic imaging data. Collectively, the Addiction working group possesses neuroimaging and genomic data obtained from over 10,000 subjects. The deadline for contributing data to the first round of analyses occurred at the beginning of May 2015. The studies performed on this data should significantly impact our understanding of the genetic and neurobiological basis of addiction.

  14. Understanding the impact of TV commercials: electrical neuroimaging.

    PubMed

    Vecchiato, Giovanni; Kong, Wanzeng; Maglione, Anton Giulio; Wei, Daming

    2012-01-01

    Today, there is a greater interest in the marketing world in using neuroimaging tools to evaluate the efficacy of TV commercials. This field of research is known as neuromarketing. In this article, we illustrate some applications of electrical neuroimaging, a discipline that uses electroencephalography (EEG) and intensive signal processing techniques for the evaluation of marketing stimuli. We also show how the proper usage of these methodologies can provide information related to memorization and attention while people are watching marketing-relevant stimuli. We note that temporal and frequency patterns of EEG signals are able to provide possible descriptors that convey information about the cognitive process in subjects observing commercial advertisements (ads). Such information could be unobtainable through common tools used in standard marketing research. Evidence of this research shows how EEG methodologies could be employed to better design new products that marketers are going to promote and to analyze the global impact of video commercials already broadcast on TV.

  15. Neuroimaging in Tourette Syndrome: Research Highlights From 2014–2015

    PubMed Central

    Greene, Deanna J.; Schlaggar, Bradley L.; Black, Kevin J.

    2015-01-01

    Tourette Syndrome (ts) is a developmental neuropsychiatric disorder of the central nervous system defined by the presence of chronic tics. While investigations of the underlying brain mechanisms have provided valuable information, a complete understanding of the pathophysiology of ts remains elusive. Neuroimaging methods provide remarkable tools for examining the human brain, and have been used to study brain structure and function in ts. In this article, we review ts neuroimaging studies published in 2014–2015. We highlight a number of noteworthy studies due to their innovative methods and interesting findings. Yet, we note that many of the recent studies share common concerns, specifically susceptibility to motion artifacts and modest sample sizes. Thus, we encourage future work to carefully address potential methodological confounds and to study larger samples to increase the potential for replicable results. PMID:26543796

  16. Functions of the human frontoparietal attention network: Evidence from neuroimaging

    PubMed Central

    Scolari, Miranda; Seidl-Rathkopf, Katharina N; Kastner, Sabine

    2016-01-01

    Human frontoparietal cortex has long been implicated as a source of attentional control. However, the mechanistic underpinnings of these control functions have remained elusive due to limitations of neuroimaging techniques that rely on anatomical landmarks to localize patterns of activation. The recent advent of topographic mapping via functional magnetic resonance imaging (fMRI) has allowed the reliable parcellation of the network into 18 independent subregions in individual subjects, thereby offering unprecedented opportunities to address a wide range of empirical questions as to how mechanisms of control operate. Here, we review the human neuroimaging literature that has begun to explore space-based, feature-based, object-based and category-based attentional control within the context of topographically defined frontoparietal cortex. PMID:27398396

  17. Functions of the human frontoparietal attention network: Evidence from neuroimaging.

    PubMed

    Scolari, Miranda; Seidl-Rathkopf, Katharina N; Kastner, Sabine

    2015-02-01

    Human frontoparietal cortex has long been implicated as a source of attentional control. However, the mechanistic underpinnings of these control functions have remained elusive due to limitations of neuroimaging techniques that rely on anatomical landmarks to localize patterns of activation. The recent advent of topographic mapping via functional magnetic resonance imaging (fMRI) has allowed the reliable parcellation of the network into 18 independent subregions in individual subjects, thereby offering u