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Improved gray matter surface based spatial statistics in neuroimaging studies.
Parvathaneni P, Lyu I, Huo Y, Rogers BP, Schilling KG, Nath V, Blaber JA, Hainline AE, Anderson AW, Woodward ND, Landman BA
(2019) Magn Reson Imaging 61: 285-295
MeSH Terms: Adult, Algorithms, Artifacts, Brain, Computer Simulation, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Gray Matter, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Neurites, Neuroimaging, Probability, White Matter
Show Abstract · Added January 31, 2020
Neuroimaging often involves acquiring high-resolution anatomical images along with other low-resolution image modalities, like diffusion and functional magnetic resonance imaging. Performing gray matter statistics with low-resolution image modalities is a challenge due to registration artifacts and partial volume effects. Gray matter surface based spatial statistics (GS-BSS) has been shown to provide higher sensitivity using gray matter surfaces compared to that of skeletonization approach of gray matter based spatial statistics which is adapted from tract based spatial statistics in diffusion studies. In this study, we improve upon GS-BSS incorporating neurite orientation dispersion and density imaging (NODDI) based search (denoted N-GSBSS) by 1) enhancing metrics mapping from native space, 2) incorporating maximum orientation dispersion index (ODI) search along surface normal, and 3) proposing applicability to other modalities, such as functional MRI (fMRI). We evaluated the performance of N-GSBSS against three baseline pipelines: volume-based registration, FreeSurfer's surface registration and ciftify pipeline for fMRI and simulation studies. First, qualitative mean ODI results are shown for N-GSBSS with and without NODDI based search in comparison with ciftify pipeline. Second, we conducted one-sample t-tests on working memory activations in fMRI to show that the proposed method can aid in the analysis of low resolution fMRI data. Finally we performed a sensitivity test in a simulation study by varying percentage change of intensity values within a region of interest in gray matter probability maps. N-GSBSS showed higher sensitivity in the simulation test compared to the other methods capturing difference between the groups starting at 10% change in the intensity values. The computational time of N-GSBSS is 68 times faster than that of traditional surface-based or 86 times faster than that of ciftify pipeline analysis.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Anatomical accuracy of standard-practice tractography algorithms in the motor system - A histological validation in the squirrel monkey brain.
Schilling KG, Gao Y, Stepniewska I, Janve V, Landman BA, Anderson AW
(2019) Magn Reson Imaging 55: 7-25
MeSH Terms: Algorithms, Animals, Brain, Brain Mapping, Diffusion Tensor Imaging, Image Processing, Computer-Assisted, Models, Anatomic, Motor Cortex, Probability, Reproducibility of Results, Saimiri, Sensitivity and Specificity, Software, White Matter
Show Abstract · Added March 26, 2019
For two decades diffusion fiber tractography has been used to probe both the spatial extent of white matter pathways and the region to region connectivity of the brain. In both cases, anatomical accuracy of tractography is critical for sound scientific conclusions. Here we assess and validate the algorithms and tractography implementations that have been most widely used - often because of ease of use, algorithm simplicity, or availability offered in open source software. Comparing forty tractography results to a ground truth defined by histological tracers in the primary motor cortex on the same squirrel monkey brains, we assess tract fidelity on the scale of voxels as well as over larger spatial domains or regional connectivity. No algorithms are successful in all metrics, and, in fact, some implementations fail to reconstruct large portions of pathways or identify major points of connectivity. The accuracy is most dependent on reconstruction method and tracking algorithm, as well as the seed region and how this region is utilized. We also note a tremendous variability in the results, even though the same MR images act as inputs to all algorithms. In addition, anatomical accuracy is significantly decreased at increased distances from the seed. An analysis of the spatial errors in tractography reveals that many techniques have trouble properly leaving the gray matter, and many only reveal connectivity to adjacent regions of interest. These results show that the most commonly implemented algorithms have several shortcomings and limitations, and choices in implementations lead to very different results. This study should provide guidance for algorithm choices based on study requirements for sensitivity, specificity, or the need to identify particular connections, and should serve as a heuristic for future developments in tractography.
Copyright © 2018 Elsevier Inc. All rights reserved.
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14 MeSH Terms
Evaluating statistical approaches to leverage large clinical datasets for uncovering therapeutic and adverse medication effects.
Choi L, Carroll RJ, Beck C, Mosley JD, Roden DM, Denny JC, Van Driest SL
(2018) Bioinformatics 34: 2988-2996
MeSH Terms: Datasets as Topic, Drug Discovery, Drug-Related Side Effects and Adverse Reactions, Electronic Health Records, Humans, Logistic Models, Probability
Show Abstract · Added March 24, 2020
Motivation - Phenome-wide association studies (PheWAS) have been used to discover many genotype-phenotype relationships and have the potential to identify therapeutic and adverse drug outcomes using longitudinal data within electronic health records (EHRs). However, the statistical methods for PheWAS applied to longitudinal EHR medication data have not been established.
Results - In this study, we developed methods to address two challenges faced with reuse of EHR for this purpose: confounding by indication, and low exposure and event rates. We used Monte Carlo simulation to assess propensity score (PS) methods, focusing on two of the most commonly used methods, PS matching and PS adjustment, to address confounding by indication. We also compared two logistic regression approaches (the default of Wald versus Firth's penalized maximum likelihood, PML) to address complete separation due to sparse data with low exposure and event rates. PS adjustment resulted in greater power than PS matching, while controlling Type I error at 0.05. The PML method provided reasonable P-values, even in cases with complete separation, with well controlled Type I error rates. Using PS adjustment and the PML method, we identify novel latent drug effects in pediatric patients exposed to two common antibiotic drugs, ampicillin and gentamicin.
Availability and implementation - R packages PheWAS and EHR are available at https://github.com/PheWAS/PheWAS and at CRAN (https://www.r-project.org/), respectively. The R script for data processing and the main analysis is available at https://github.com/choileena/EHR.
Supplementary information - Supplementary data are available at Bioinformatics online.
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(Na1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance.
Kroncke BM, Glazer AM, Smith DK, Blume JD, Roden DM
(2018) Circ Genom Precis Med 11: e002095
MeSH Terms: Animals, Cell Line, Humans, Models, Genetic, Mutation, NAV1.5 Voltage-Gated Sodium Channel, Penetrance, Probability, Statistics, Nonparametric, Uncertainty
Show Abstract · Added March 26, 2019
BACKGROUND - Accurately predicting the impact of rare nonsynonymous variants on disease risk is an important goal in precision medicine. Variants in the cardiac sodium channel (protein Na1.5; voltage-dependent cardiac Na+ channel) are associated with multiple arrhythmia disorders, including Brugada syndrome and long QT syndrome. Rare variants also occur in ≈1% of unaffected individuals. We hypothesized that in vitro electrophysiological functional parameters explain a statistically significant portion of the variability in disease penetrance.
METHODS - From a comprehensive literature review, we quantified the number of carriers presenting with and without disease for 1712 reported variants. For 356 variants, data were also available for 5 Na1.5 electrophysiological parameters: peak current, late/persistent current, steady-state V1/2 of activation and inactivation, and recovery from inactivation.
RESULTS - We found that peak and late current significantly associate with Brugada syndrome (<0.001; ρ=-0.44; Spearman rank test) and long QT syndrome disease penetrance (<0.001; ρ=0.37). Steady-state V1/2 activation and recovery from inactivation associate significantly with Brugada syndrome and long QT syndrome penetrance, respectively. Continuous estimates of disease penetrance align with the current American College of Medical Genetics classification paradigm.
CONCLUSIONS - Na1.5 in vitro electrophysiological parameters are correlated with Brugada syndrome and long QT syndrome disease risk. Our data emphasize the value of in vitro electrophysiological characterization and incorporating counts of affected and unaffected carriers to aid variant classification. This quantitative analysis of the electrophysiological literature should aid the interpretation of Na1.5 variant electrophysiological abnormalities and help improve Na1.5 variant classification.
© 2018 American Heart Association, Inc.
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10 MeSH Terms
Subjective value representations during effort, probability and time discounting across adulthood.
Seaman KL, Brooks N, Karrer TM, Castrellon JJ, Perkins SF, Dang LC, Hsu M, Zald DH, Samanez-Larkin GR
(2018) Soc Cogn Affect Neurosci 13: 449-459
MeSH Terms: Adult, Aged, Aged, 80 and over, Aging, Brain, Choice Behavior, Cognition, Decision Making, Delay Discounting, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Motivation, Neuropsychological Tests, Physical Exertion, Probability, Psychomotor Performance, Reward, Young Adult
Show Abstract · Added April 15, 2019
Every day, humans make countless decisions that require the integration of information about potential benefits (i.e. rewards) with other decision features (i.e. effort required, probability of an outcome or time delays). Here, we examine the overlap and dissociation of behavioral preferences and neural representations of subjective value in the context of three different decision features (physical effort, probability and time delays) in a healthy adult life span sample. While undergoing functional neuroimaging, participants (N = 75) made incentive compatible choices between a smaller monetary reward with lower physical effort, higher probability, or a shorter time delay versus a larger monetary reward with higher physical effort, lower probability, or a longer time delay. Behavioral preferences were estimated from observed choices, and subjective values were computed using individual hyperbolic discount functions. We found that discount rates were uncorrelated across tasks. Despite this apparent behavioral dissociation between preferences, we found overlapping subjective value-related activity in the medial prefrontal cortex across all three tasks. We found no consistent evidence for age differences in either preferences or the neural representations of subjective value across adulthood. These results suggest that while the tolerance of decision features is behaviorally dissociable, subjective value signals share a common representation across adulthood.
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Communication About the Probability of Cancer in Indeterminate Pulmonary Nodules.
Maiga AW, Deppen SA, Massion PP, Callaway-Lane C, Pinkerman R, Dittus RS, Lambright ES, Nesbitt JC, Grogan EL
(2018) JAMA Surg 153: 353-357
MeSH Terms: Aged, Communication, Documentation, Female, Guideline Adherence, Humans, Lung Neoplasms, Male, Medical Records, Middle Aged, Practice Guidelines as Topic, Probability, Retrospective Studies, Risk Assessment, Risk Factors, Solitary Pulmonary Nodule
Show Abstract · Added January 29, 2018
Importance - Clinical guidelines recommend that clinicians estimate the probability of malignancy for patients with indeterminate pulmonary nodules (IPNs) larger than 8 mm. Adherence to these guidelines is unknown.
Objectives - To determine whether clinicians document the probability of malignancy in high-risk IPNs and to compare these quantitative or qualitative predictions with the validated Mayo Clinic Model.
Design, Setting, and Participants - Single-institution, retrospective cohort study of patients from a tertiary care Department of Veterans Affairs hospital from January 1, 2003, through December 31, 2015. Cohort 1 included 291 veterans undergoing surgical resection of known or suspected lung cancer from January 1, 2003, through December 31, 2015. Cohort 2 included a random sample of 239 veterans undergoing inpatient or outpatient pulmonary evaluation of IPNs at the hospital from January 1, 2003, through December 31, 2012.
Exposures - Clinician documentation of the quantitative or qualitative probability of malignancy.
Main Outcomes and Measures - Documentation from pulmonary and/or thoracic surgery clinicians as well as information from multidisciplinary tumor board presentations was reviewed. Any documented quantitative or qualitative predictions of malignancy were extracted and summarized using descriptive statistics. Clinicians' predictions were compared with risk estimates from the Mayo Clinic Model.
Results - Of 291 patients in cohort 1, 282 (96.9%) were men; mean (SD) age was 64.6 (9.0) years. Of 239 patients in cohort 2, 233 (97.5%) were men; mean (SD) age was 65.5 (10.8) years. Cancer prevalence was 258 of 291 cases (88.7%) in cohort 1 and 110 of 225 patients with a definitive diagnosis (48.9%) in cohort 2. Only 13 patients (4.5%) in cohort 1 and 3 (1.3%) in cohort 2 had a documented quantitative prediction of malignancy prior to tissue diagnosis. Of the remaining patients, 217 of 278 (78.1%) in cohort 1 and 149 of 236 (63.1%) in cohort 2 had qualitative statements of cancer risk. In cohort 2, 23 of 79 patients (29.1%) without any documented malignancy risk statements had a final diagnosis of cancer. Qualitative risk statements were distributed among 32 broad categories. The most frequently used statements aligned well with Mayo Clinic Model predictions for cohort 1 compared with cohort 2. The median Mayo Clinic Model-predicted probability of cancer was 68.7% (range, 2.4%-100.0%). Qualitative risk statements roughly aligned with Mayo predictions.
Conclusions and Relevance - Clinicians rarely provide quantitative documentation of cancer probability for high-risk IPNs, even among patients drawn from a broad range of cancer probabilities. Qualitative statements of cancer risk in current practice are imprecise and highly variable. A standard scale that correlates with predicted cancer risk for IPNs should be used to communicate with patients and other clinicians.
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16 MeSH Terms
The discrepancy among single nucleotide variants detected by DNA and RNA high throughput sequencing data.
Guo Y, Zhao S, Sheng Q, Samuels DC, Shyr Y
(2017) BMC Genomics 18: 690
MeSH Terms: Databases, Nucleic Acid, Genotype, Heterozygote, High-Throughput Nucleotide Sequencing, Mutation, Polymorphism, Single Nucleotide, Probability, Sequence Analysis, DNA, Sequence Analysis, RNA
Show Abstract · Added March 21, 2018
BACKGROUND - High throughput sequencing technology enables the both the human genome and transcriptome to be screened at the single nucleotide resolution. Tools have been developed to infer single nucleotide variants (SNVs) from both DNA and RNA sequencing data. To evaluate how much difference can be expected between DNA and RNA sequencing data, and among tissue sources, we designed a study to examine the single nucleotide difference among five sources of high throughput sequencing data generated from the same individual, including exome sequencing from blood, tumor and adjacent normal tissue, and RNAseq from tumor and adjacent normal tissue.
RESULTS - Through careful quality control and analysis of the SNVs, we found little difference between DNA-DNA pairs (1%-2%). However, between DNA-RNA pairs, SNV differences ranged anywhere from 10% to 20%.
CONCLUSIONS - Only a small portion of these differences can be explained by RNA editing. Instead, the majority of the DNA-RNA differences should be attributed to technical errors from sequencing and post-processing of RNAseq data. Our analysis results suggest that SNV detection using RNAseq is subject to high false positive rates.
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9 MeSH Terms
Category-specific learned attentional bias to object parts.
Chua KW, Gauthier I
(2016) Atten Percept Psychophys 78: 44-51
MeSH Terms: Adolescent, Attention, Cognition, Female, Humans, Learning, Male, Photic Stimulation, Probability, Reaction Time, Young Adult
Show Abstract · Added February 23, 2016
Humans can selectively attend to information in visual scenes. Learning from previous experiences plays a role in how visual attention is subsequently deployed. For example, visual search times are faster in areas that are statistically more likely to contain a target (Jiang and Swallow in Cognition, 126(3), 378-390, 2013). Here, we examined whether similar attentional biases can be created for different locations on complex objects as a function of their category, based on a history of these locations containing a target. Subjects performed a visual search task in the context of novel objects called Greebles. The target appeared in one half (e.g., top) of the Greebles 89 % of the time and in the other half (e.g., bottom) 11 % of the time. We found a reaction time advantage when the target was located in a "target-rich" region, even after target location probabilities were equated. This indicates that attentional biases can be associated not only with regions of space but also with specific object features, or at least with locations in an object-based frame of reference.
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11 MeSH Terms
Automatic detection of the anterior and posterior commissures on MRI scans using regression forests.
Liu Y, Dawant BM
(2014) Conf Proc IEEE Eng Med Biol Soc 2014: 1505-8
MeSH Terms: Algorithms, Brain, Brain Mapping, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Learning, Magnetic Resonance Imaging, Models, Statistical, Normal Distribution, Probability, Programming Languages, Regression Analysis, Reproducibility of Results, Software
Show Abstract · Added February 19, 2015
Identification of the anterior and posterior commissure is crucial in stereotactic and functional neurosurgery, human brain mapping, and medical image processing. We present a learning-based algorithm to automatically and rapidly localize these landmarks using random forests regression. Given a point in the image, we extract a set of multi-scale long-range textural features, and associate a probability for this point to be the landmark. We build random forests models to learn the relationship between the value of these features and the probability of a point to be a landmark point. Three-stage coarse-to-fine models are trained for AC and PC separately using down-sampled by 4, down-sampled by 2, and the original images. Testing is performed in a hierarchical approach to first obtain a rough estimation at the coarse level and then fine-tune the landmark position. We extensively evaluate our method in a leave-one-out fashion using a large dataset of 100 T1-weighted images. We also compare our method to the state-of-art AC/PC detection methods including an atlas-based approach with six well-established nonrigid registration algorithms and a publicly available implementation of a model-based approach. Our method results in an overall error of 0.84±0.41mm for AC, 0.83±0.36mm for PC and a maximum error of 2.04mm; it performs significantly better than the model-based AC/PC detection method we compare it to and better than three of the nonrigid registration methods. It is much faster than nonrigid registration methods.
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15 MeSH Terms
Impaired effort allocation in patients with schizophrenia.
Treadway MT, Peterman JS, Zald DH, Park S
(2015) Schizophr Res 161: 382-5
MeSH Terms: Adult, Anticipation, Psychological, Decision Making, Female, Humans, Male, Motivation, Probability, Psychological Tests, Reward, Schizophrenia, Schizophrenic Psychology
Show Abstract · Added July 28, 2015
A hallmark of negative symptoms in schizophrenia is reduced motivation and goal directed behavior. While preclinical models suggest that blunted striatal dopamine levels can produce such reductions, this mechanism is inconsistent with evidence for enhanced striatal dopamine levels in schizophrenia. In seeking to reconcile this discrepancy, one possibility is that negative symptoms reflect a failure of striatal motivational systems to mobilize appropriately in response to reward-related information. In the present study, we used a laboratory effort-based decision-making task in a sample of patients with schizophrenia and healthy controls to examine allocation of effort in exchange for varying levels of monetary reward. We found that patients and controls did not differ in the overall amount of effort expenditure, but patients made significantly less optimal choices in terms of maximizing rewards. These results provide further evidence for a selective deficit in the ability of schizophrenia patients to utilize environmental cues to guide reward-seeking behavior.
Copyright © 2014 Elsevier B.V. All rights reserved.
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12 MeSH Terms