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Alexander Drzezga,
J Alex Becker,
Koene R A Van Dijk,
Aishwarya Sreenivasan,
Tanveer Talukdar,
Caroline Sullivan,
Aaron P Schultz,
Jorge Sepulcre,
Deepti Putcha, Doug Greve,
Keith A Johnson,
Reisa A Sperling
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ABSTRACT: Disruption of functional connectivity between brain regions may represent an early functional consequence of β-amyloid pathology prior to clinical Alzheimer's disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity. Significant disruptions of whole-brain connectivity were found in amyloid-positive patients with mild cognitive impairment in typical cortical hubs (posterior cingulate cortex/precuneus), strongly overlapping with regional hypometabolism. Subtle connectivity disruptions and hypometabolism were already present in amyloid-positive asymptomatic subjects. Voxel-based morphometry measures indicate that these findings were not solely a consequence of regional atrophy. Whole-brain connectivity values and metabolism showed a positive correlation with each other and a negative correlation with amyloid burden. These results indicate that disruption of functional connectivity and hypometabolism may represent early functional consequences of emerging molecular Alzheimer's disease pathology, evolving prior to clinical onset of dementia. The spatial overlap between hypometabolism and disruption of connectivity in cortical hubs points to a particular susceptibility of these regions to early Alzheimer's-type neurodegeneration and may reflect a link between synaptic dysfunction and functional disconnection.
Brain 06/2011; 134(Pt 6):1635-46. · 9.46 Impact Factor
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ABSTRACT: Functional magnetic resonance imaging (fMRI) holds significant potential to aid in the development of early interventions to improve memory function, and to assess longitudinal change in memory systems in aging and early Alzheimer's disease (AD). However, the test-retest reliability of hippocampal activation and of "beneficial" deactivation in the precuneus has yet to be fully established during memory encoding tasks in older subjects. Using a mixed block and event-related face-name associative encoding paradigm, we assessed the reliability of hippocampal activation and default network deactivation over a 4- to 6-week interscan interval in 27 older individuals who were cognitively normal [Clinical Dementia Rating (CDR) Scale = 0; n = 18] or mildly impaired (CDR = 0.5; n = 9). Reliability was assessed in whole brain maps and regions of interest using both a full-task paradigm of six functional runs as well as an abbreviated paradigm of the first two functional runs, which would be advantageous for use in clinical trials. We found reliable hippocampal signal response across both block- and event-related designs in the right hippocampus. Comparable reliability in hippocampal activation was found in the full and the abbreviated paradigm. Similar reliability in hippocampal activation was observed across both CDR groups overall, but the CDR 0.5 group was more variable in left hippocampal activity. Task-related deactivation in the precuneus demonstrated much greater variability than hippocampal activation in all analyses. Overall, these results are encouraging for the utility of fMRI in "Proof of Concept" clinical trials investigating the efficacy of potentially therapeutic agents for treatment of age-related memory changes, cognitive impairment, and early AD.
Human Brain Mapping 01/2011; 32(12):2027-44. · 5.88 Impact Factor
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Gregory G Brown,
Gregory McCarthy,
Amanda Bischoff-Grethe,
Burak Ozyurt, Doug Greve,
Steven G Potkin,
Jessica A Turner,
Randy Notestine,
Vince D Calhoun,
Judy M Ford,
Daniel Mathalon,
Dara S Manoach,
Syam Gadde,
Gary H Glover,
Cynthia G Wible,
Aysenil Belger,
Randy L Gollub,
John Lauriello,
Daniel O'Leary,
Kelvin O Lim
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ABSTRACT: Correlations of cognitive functioning with brain activation during a sternberg item recognition paradigm (SIRP) were investigated in patients with schizophrenia and in healthy controls studied at 8 sites. To measure memory scanning times, 4 response time models were fit to SIRP data. The best fitting model assumed exhaustive serial memory scanning followed by self-terminating memory search and involved one intercept parameter to represent SIRP processes not contributing directly to memory scanning. Patients displayed significantly longer response times with increasing memory load and differed on the memory scanning, memory search, and intercept parameters of the best fitting probability model. Groups differed in the correlation between the memory scanning parameter and linear brain response to increasing memory load within left inferior and left middle frontal gyrus, bilateral caudate, and right precuneus. The pattern of findings in these regions indicated that high scanning capacity was associated with high neural capacity among healthy subjects but that scanning speed was uncoupled from brain response to increasing memory load among schizophrenia patients. Group differences in correlation of the best fitting model's scanning parameter with a quadratic trend in brain response to increasing memory load suggested inefficient or disordered patterns of neural inhibition among individuals with schizophrenia, especially in the left perirhinal and entorhinal cortices. The results show at both cognitive and neural levels that disordered memory scanning contributes to deficient SIRP performance among schizophrenia patients.
Schizophrenia Bulletin 12/2008; 35(1):32-46. · 8.80 Impact Factor
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ABSTRACT: The clinical phenotype of Huntington's disease (HD) is far more complex and variable than depictions of it as a progressive movement disorder dominated by neostriatal pathology represent. The availability of novel neuro-imaging methods has enabled us to evaluate cerebral cortical changes in HD, which we have found to occur early and to be topographically selective. What is less clear, however, is how these changes influence the clinical expression of the disease. In this study, we used a high-resolution surface based analysis of in vivo MRI data to measure cortical thickness in 33 individuals with HD, spanning the spectrum of disease and 22 age- and sex-matched controls. We found close relationships between specific functional and cognitive measures and topologically specific cortical regions. We also found that distinct motor phenotypes were associated with discrete patterns of cortical thinning. The selective topographical associations of cortical thinning with clinical features of HD suggest that we are not simply correlating global worsening with global cortical degeneration. Our results indicate that cortical involvement contributes to important symptoms, including those that have been ascribed primarily to the striatum, and that topologically selective changes in the cortex might explain much of the clinical heterogeneity found in HD. Additionally, a significant association between regional cortical thinning and total functional capacity, currently the leading primary outcome measure used in neuroprotection trials for HD, establishes cortical MRI morphometry as a potential biomarker of disease progression.
Brain 05/2008; 131(Pt 4):1057-68. · 9.46 Impact Factor
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ABSTRACT: Darwin regarded emotions as predispositions to act adaptively, thereby suggesting that characteristic body movements are associated with each emotional state. To this date, investigations of emotional cognition have predominantly concentrated on processes associated with viewing facial expressions. However, expressive body movements may be just as important for understanding the neurobiology of emotional behavior. Here, we used functional MRI to clarify how the brain recognizes happiness or fear expressed by a whole body. Our results indicate that observing fearful body expressions produces increased activity in brain areas narrowly associated with emotional processes and that this emotion-related activity occurs together with activation of areas linked with representation of action and movement. The mechanism of fear contagion hereby suggested may automatically prepare the brain for action.
Proceedings of the National Academy of Sciences 12/2004; 101(47):16701-6. · 9.68 Impact Factor
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ABSTRACT: the "licensee" (either an individual or a single entity), and CorTechs. For the purposes of this EULA, FreeSurfer includes computer software, documentation and sample datasets, the associated media, any printed materials, and any online or electronic documentation. By installing, copying, or otherwise using FreeSurfer, the licensee agrees to be bound by the terms of this EULA. If you do not agree to the terms of this EULA, then you may not install, copy or otherwise use FreeSurfer, and you are required to destroy the CD and remove any files that you may have already installed. 1. GRANT OF LICENSE This EULA grants the licensee the following rights: Software. The licensee may install one copy of FreeSurfer on a single computer. Network Use. The licensee may use FreeSurfer over an internal network, and the licensee may distribute FreeSurfer to other computers over an internal network. Documentation. The licensee may make a copy of the documentation for internal use only. 2. LIMITA
02/2002;
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ABSTRACT: Event-related functional magnetic resonance imaging was used to investigate the localization of syntactic processing in sentence comprehension. Matched pairs of sentences containing identical lexical items were compared. One member of the pair consisted of a syntactically simpler sentence, containing a subject relativized clause. The second member of the pair consisted of a syntactically more complex sentence, containing an object relativized clause. Ten subjects made plausibility judgments about the sentences, which were presented one word at a time on a computer screen. There was an increase in BOLD hemodynamic signal in response to the presentation of all sentences compared to fixation in both right and left occipital cortex, the left perisylvian cortex, and the left premotor and motor areas. BOLD signal increased in the left angular gyrus when subjects processed the complex portion of syntactically more complex sentences. This study shows that a hemodynamic response associated with processing the syntactically complex portions of a sentence can be localized to one part of the dominant perisylvian association cortex.
Human Brain Mapping 02/2002; 15(1):26-38. · 5.88 Impact Factor
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Randy L Gollub,
Stephanie J. Bird,
E. N. (Emery N.) Brown,
Bruce Fischl,
Nancy Kanwisher,
Kennedy,
David N. (David Nelson,
Dara Manoach,
Jennifer R Melcher,
Christopher Moore, [......],
Joe Mandeville,
Bruce Robert Rosen,
Cary Savage,
Robert Savoy,
A Gregory Sorensen,
Tuch,
David Solomon,
Wim Vanduffel,
Mark Geoffrey Vangel,
George Bush
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ABSTRACT: Provides information relevant to the conduct and interpretation of human brain mapping studies. Provides in-depth coverage of the physics of image formation, mechanisms of image contrast, and the physiological basis for image signals. Parenchymal and cerebrovascular neuroanatomy and application of sophisticated structural analysis algorithms for segmentation and registration of functional data are discussed. Additional topics include fMRI experimental design including block design, event related and exploratory data analysis methods, and building and applying statistical models for fMRI data. Human subject issues including informed consent, institutional review board requirements and safety in the high field environment are also presented. Probability, linear algebra, differential equations, and introductory or college-level subjects in neurobiology, physiology, and physics is required.
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Randy L Gollub,
Robert B. Banzett,
Divya S Bolar,
Randy Buckner,
Bradford Dickerson,
John D E Gabrieli,
Susan Whitfield-Gabrieli, Doug Greve,
Nouchine Hadjikhani,
Karl Helmer, [......],
Sonia Pujol,
Bruce Robert Rosen,
David Salat,
Robert Savoy,
Dan Sodickson,
A Gregory Sorensen,
Christina Triantafyllou,
Mark Geoffrey Vangel,
Lawrence Wald,
Anastasia Yendiki
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ABSTRACT: This team taught, multidisciplinary course covers the fundamentals of magnetic resonance imaging relevant to the conduct and interpretation of human brain mapping studies. The challenges inherent in advancing our knowledge about brain function using fMRI are presented first to put the work in context. The course then provides in depth coverage of the physics of image formation, mechanisms of image contrast, and the physiological basis for image signals. Parenchymal and cerebrovascular neuroanatomy and application of sophisticated structural analysis algorithms for segmentation and registration of functional data are discussed. Additional topics include fMRI experimental design including block design, event related and exploratory data analysis methods, building and applying statistical models for fMRI data. Human subjects issues including informed consent, institutional review board requirements and safety in the high field environment are presented.
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Randy L Gollub,
Robert Savoy,
Lawrence Wald,
Robert B. Banzett,
Bradford C Dickerson,
Jennifer R Melcher,
Kennedy,
David N. (David Nelson,
Tuch,
David Solomon, [......],
Mark Geoffrey Vangel,
Rick Hoge,
Anne Blood,
Nouchine Hadjikhani,
Christopher Moore,
David Salat,
Sigalovsky,
Irina S,
Steven M Stufflebeam,
Martin Zalesky
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ABSTRACT: Provides information relevant to the conduct and interpretation of human brain mapping studies. Provides in-depth coverage of the physics of image formation, mechanisms of image contrast, and the physiological basis for image signals. Parenchymal and cerebrovascular neuroanatomy and application of sophisticated structural analysis algorithms for segmentation and registration of functional data are discussed. Additional topics include fMRI experimental design including block design, event related and exploratory data analysis methods, and building and applying statistical models for fMRI data. Human subject issues including informed consent, institutional review board requirements and safety in the high field environment are also presented. Probability, linear algebra, differential equations, and introductory or college-level subjects in neurobiology, physiology, and physics is required.
