@article {bai2016activity, title = {An activity index for raw accelerometry data and its comparison with other activity metrics}, journal = {PloS ONE}, volume = {11}, number = {8}, year = {2016}, pages = {e0160644}, publisher = {Public Library of Science}, author = {Bai, Jiawei and Di, Chongzhi and Xiao, Luo and Evenson, Kelly R and LaCroix, Andrea Z and Crainiceanu, Ciprian M and Buchner, David M} } @article {819, title = {Analytic programming with FMRI data: a quick-start guide for statisticians using R.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e89470}, abstract = {

Functional magnetic resonance imaging (fMRI) is a thriving field that plays an important role in medical imaging analysis, biological and neuroscience research and practice. This manuscript gives a didactic introduction to the statistical analysis of fMRI data using the R project, along with the relevant R code. The goal is to give statisticians who would like to pursue research in this area a quick tutorial for programming with fMRI data. References of relevant packages and papers are provided for those interested in more advanced analysis.

}, keywords = {Brain, brain mapping, Humans, Magnetic Resonance Imaging, Programming Languages}, issn = {1932-6203}, doi = {10.1371/journal.pone.0089470}, author = {Eloyan, Ani and Li, Shanshan and Muschelli, John and Pekar, Jim J and Mostofsky, Stewart H and Caffo, Brian S} } @article {836, title = {Brain mediators of the effects of noxious heat on pain.}, journal = {Pain}, volume = {155}, year = {2014}, month = {2014 Aug}, pages = {1632-48}, abstract = {

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain.

}, issn = {1872-6623}, doi = {10.1016/j.pain.2014.05.015}, author = {Atlas, Lauren Y and Lindquist, Martin A and Bolger, Niall and Wager, Tor D} } @article {835, title = {Evaluating dynamic bivariate correlations in resting-state fMRI: a comparison study and a new approach.}, journal = {Neuroimage}, volume = {101}, year = {2014}, month = {2014 Nov 1}, pages = {531-46}, abstract = {

To date, most functional Magnetic Resonance Imaging (fMRI) studies have assumed that the functional connectivity (FC) between time series from distinct brain regions is constant across time. However, recently, there has been an increased interest in quantifying possible dynamic changes in FC during fMRI experiments, as it is thought that this may provide insight into the fundamental workings of brain networks. In this work we focus on the specific problem of estimating the dynamic behavior of pair-wise correlations between time courses extracted from two different regions of the brain. We critique the commonly used sliding-window technique, and discuss some alternative methods used to model volatility in the finance literature that could also prove to be useful in the neuroimaging setting. In particular, we focus on the Dynamic Conditional Correlation (DCC) model, which provides a model-based approach towards estimating dynamic correlations. We investigate the properties of several techniques in a series of simulation studies and find that DCC achieves the best overall balance between sensitivity and specificity in detecting dynamic changes in correlations. We also investigate its scalability beyond the bivariate case to demonstrate its utility for studying dynamic correlations between more than two brain regions. Finally, we illustrate its performance in an application to test-retest resting state fMRI data.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.06.052}, author = {Lindquist, Martin A and Xu, Yuting and Nebel, Mary Beth and Caffo, Brain S} } @article {790, title = {Health effects of lesion localization in multiple sclerosis: spatial registration and confounding adjustment.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e107263}, abstract = {

Brain lesion localization in multiple sclerosis (MS) is thought to be associated with the type and severity of adverse health effects. However, several factors hinder statistical analyses of such associations using large MRI datasets: 1) spatial registration algorithms developed for healthy individuals may be less effective on diseased brains and lead to different spatial distributions of lesions; 2) interpretation of results requires the careful selection of confounders; and 3) most approaches have focused on voxel-wise regression approaches. In this paper, we evaluated the performance of five registration algorithms and observed that conclusions regarding lesion localization can vary substantially with the choice of registration algorithm. Methods for dealing with confounding factors due to differences in disease duration and local lesion volume are introduced. Voxel-wise regression is then extended by the introduction of a metric that measures the distance between a patient-specific lesion mask and the population prevalence map.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0107263}, author = {Eloyan, Ani and Shou, Haochang and Shinohara, Russell T and Sweeney, Elizabeth M and Nebel, Mary Beth and Cuzzocreo, Jennifer L and Calabresi, Peter A and Reich, Daniel S and Lindquist, Martin A and Crainiceanu, Ciprian M} } @article {837, title = {A hierarchical model for simultaneous detection and estimation in multi-subject fMRI studies.}, journal = {Neuroimage}, volume = {98}, year = {2014}, month = {2014 Sep}, pages = {61-72}, abstract = {

In this paper we introduce a new hierarchical model for the simultaneous detection of brain activation and estimation of the shape of the hemodynamic response in multi-subject fMRI studies. The proposed approach circumvents a major stumbling block in standard multi-subject fMRI data analysis, in that it both allows the shape of the hemodynamic response function to vary across region and subjects, while still providing a straightforward way to estimate population-level activation. An efficient estimation algorithm is presented, as is an inferential framework that allows for not only tests of activation, but also tests for deviations from some canonical shape. The model is validated through simulations and application to a multi-subject fMRI study of thermal pain.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.04.052}, author = {Degras, David and Lindquist, Martin A} } @article {815, title = {Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.}, journal = {Neurobiol Dis}, volume = {74C}, year = {2014}, month = {2014 Nov 7}, pages = {58-65}, abstract = {

There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play.

}, issn = {1095-953X}, doi = {10.1016/j.nbd.2014.10.019}, author = {Coughlin, Jennifer M and Wang, Yuchuan and Munro, Cynthia A and Ma, Shuangchao and Yue, Chen and Chen, Shaojie and Airan, Raag and Kim, Pearl K and Adams, Ashley V and Garcia, Cinthya and Higgs, Cecilia and Sair, Haris I and Sawa, Akira and Smith, Gwenn and Lyketsos, Constantine G and Caffo, Brian and Kassiou, Michael and Guilarte, Tomas R and Pomper, Martin G} } @article {791, title = {Predicting human movement with multiple accelerometers using movelets.}, journal = {Med Sci Sports Exerc}, volume = {46}, year = {2014}, month = {2014 Sep}, pages = {1859-66}, abstract = {

PURPOSE: The study aims were 1) to develop transparent algorithms that use short segments of training data for predicting activity types and 2) to compare the prediction performance of the proposed algorithms using single accelerometers and multiple accelerometers.

METHODS: Sixteen participants (age, 80.6 yr (4.8 yr); body mass index, 26.1 kg{\textperiodcentered}m (2.5 kg{\textperiodcentered}m)) performed 15 lifestyle activities in the laboratory, each wearing three accelerometers at the right hip and left and right wrists. Triaxial accelerometry data were collected at 80 Hz using ActiGraph GT3X+. Prediction algorithms were developed, which, instead of extracting features, build activity-specific dictionaries composed of short signal segments called movelets. Three alternative approaches were proposed to integrate the information from the multiple accelerometers.

RESULTS: With at most several seconds of training data per activity, the prediction accuracy at the second-level temporal resolution was very high for lying, standing, normal/fast walking, and standing up from a chair (the median prediction accuracy ranged from 88.2\% to 99.9\% on the basis of the single-accelerometer movelet approach). For these activities, wrist-worn accelerometers performed almost as well as hip-worn accelerometers (the median difference in accuracy between wrist and hip ranged from -2.7\% to 5.8\%). Modest improvements in prediction accuracy were achieved by integrating information from multiple accelerometers.

DISCUSSION AND CONCLUSIONS: It is possible to achieve high prediction accuracy at the second-level temporal resolution with very limited training data. To increase prediction accuracy from the simultaneous use of multiple accelerometers, a careful selection of integrative approaches is required.

}, issn = {1530-0315}, doi = {10.1249/MSS.0000000000000285}, author = {He, Bing and Bai, Jiawei and Zipunnikov, Vadim V and Koster, Annemarie and Caserotti, Paolo and Lange-Maia, Brittney and Glynn, Nancy W and Harris, Tamara B and Crainiceanu, Ciprian M} } @article {834, title = {Separate neural representations for physical pain and social rejection.}, journal = {Nat Commun}, volume = {5}, year = {2014}, month = {2014}, pages = {5380}, abstract = {

Current theories suggest that physical pain and social rejection share common neural mechanisms, largely by virtue of overlapping functional magnetic resonance imaging (fMRI) activity. Here we challenge this notion by identifying distinct multivariate fMRI patterns unique to pain and rejection. Sixty participants experience painful heat and warmth and view photos of ex-partners and friends on separate trials. FMRI pattern classifiers discriminate pain and rejection from their respective control conditions in out-of-sample individuals with 92\% and 80\% accuracy. The rejection classifier performs at chance on pain, and vice versa. Pain- and rejection-related representations are uncorrelated within regions thought to encode pain affect (for example, dorsal anterior cingulate) and show distinct functional connectivity with other regions in a separate resting-state data set (N=91). These findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans.

}, issn = {2041-1723}, doi = {10.1038/ncomms6380}, author = {Woo, Choong-Wan and Koban, Leonie and Kross, Ethan and Lindquist, Martin A and Banich, Marie T and Ruzic, Luka and Andrews-Hanna, Jessica R and Wager, Tor D} } @article {792, title = {Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI.}, journal = {Neuroimage}, volume = {102 Pt 2}, year = {2014}, month = {2014 Nov 15}, pages = {938-44}, abstract = {

Resting-state functional magnetic resonance imaging (rs-fMRI) is used to investigate synchronous activations in spatially distinct regions of the brain, which are thought to reflect functional systems supporting cognitive processes. Analyses are often performed using seed-based correlation analysis, allowing researchers to explore functional connectivity between data in a seed region and the rest of the brain. Using scan-rescan rs-fMRI data, we investigate how well the subject-specific seed-based correlation map from the second replication of the study can be predicted using data from the first replication. We show that one can dramatically improve prediction of subject-specific connectivity by borrowing strength from the group correlation map computed using all other subjects in the study. Even more surprisingly, we found that the group correlation map provided a better prediction of a subject{\textquoteright}s connectivity than the individual{\textquoteright}s own data. While further discussion and experimentation are required to understand how this can be used in practice, results indicate that shrinkage-based methods that borrow strength from the population mean should play a role in rs-fMRI data analysis.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.05.043}, author = {Shou, Haochang and Eloyan, Ani and Nebel, Mary Beth and Mejia, Amanda and Pekar, James J and Mostofsky, Stewart and Caffo, Brian and Lindquist, Martin A and Crainiceanu, Ciprian M} } @article {820, title = {Successful implementation of a unit-based quality nurse to reduce central line-associated bloodstream infections.}, journal = {Am J Infect Control}, volume = {42}, year = {2014}, month = {2014 Feb}, pages = {139-43}, abstract = {

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSI) are an important cause of patient morbidity and mortality. Novel strategies to prevent CLABSI are needed.

METHODS: We described a quasiexperimental study to examine the effect of the presence of a unit-based quality nurse (UQN) dedicated to perform patient safety and infection control activities with a focus on CLABSI prevention in a surgical intensive care unit (SICU).

RESULTS: From July 2008 to March 2012, there were 3,257 SICU admissions; CL utilization ratio was 0.74 (18,193 CL-days/24,576 patient-days). The UQN program began in July 2010; the nurse was present for 30\% (193/518) of the days of the intervention period of July 2010 to March 2012. The average CLABSI rate was 5.0 per 1,000 CL-days before the intervention and 1.5 after the intervention and decreased by 5.1\% (P = .005) for each additional 1\% of days of the month that the UQN was present, even after adjusting for CLABSI rates in other adult intensive care units, time, severity of illness, and Comprehensive Unit-based Safety Program participation (5.1\%, P = .004). Approximately 11.4 CLABSIs were prevented.

CONCLUSION: The presence of a UQN dedicated to perform infection control activities may be an effective strategy for CLABSI reduction.

}, keywords = {Adult, Catheter-Related Infections, Catheterization, Central Venous, Humans, Infection Control, Intensive Care Units, Nurses, Quality Control, Quality of Health Care}, issn = {1527-3296}, doi = {10.1016/j.ajic.2013.08.006}, author = {Thom, Kerri A and Li, Shanshan and Custer, Melissa and Preas, Michael Anne and Rew, Cindy D and Cafeo, Christina and Leekha, Surbhi and Caffo, Brian S and Scalea, Thomas M and Lissauer, Matthew E} } @article {806, title = {Acute lesions that impair affective empathy.}, journal = {Brain}, volume = {136}, year = {2013}, month = {2013 Aug}, pages = {2539-49}, abstract = {

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy--making inferences about how another person feels--engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy.

}, keywords = {Adult, Aged, Brain, Brain Ischemia, brain mapping, Cognition, Emotions, Empathy, Female, Functional Laterality, Humans, Male, Middle Aged, Nerve Net, Social Perception, Stroke}, issn = {1460-2156}, doi = {10.1093/brain/awt177}, author = {Leigh, Richard and Oishi, Kenichi and Hsu, John and Lindquist, Martin and Gottesman, Rebecca F and Jarso, Samson and Crainiceanu, Ciprian and Mori, Susumu and Hillis, Argye E} } @article {843, title = {Cloak and DAG: a response to the comments on our comment.}, journal = {Neuroimage}, volume = {76}, year = {2013}, month = {2013 Aug 1}, pages = {446-9}, abstract = {

Our original comment (Lindquist and Sobel, 2011) made explicit the types of assumptions neuroimaging researchers are making when directed graphical models (DGMs), which include certain types of structural equation models (SEMs), are used to estimate causal effects. When these assumptions, which many researchers are not aware of, are not met, parameters of these models should not be interpreted as effects. Thus it is imperative that neuroimaging researchers interested in issues involving causation, for example, effective connectivity, consider the plausibility of these assumptions for their particular problem before using SEMs. In cases where these additional assumptions are not met, researchers may be able to use other methods and/or design experimental studies where the use of unrealistic assumptions can be avoided. Pearl does not disagree with anything we stated. However, he takes exception to our use of potential outcomes{\textquoteright} notation, which is the standard notation used in the statistical literature on causal inference, and his comment is devoted to promoting his alternative conventions. Glymour{\textquoteright}s comment is based on three claims that he inappropriately attributes to us. Glymour is also more optimistic than us about the potential of using directed graphical models (DGMs) to discover causal relations in neuroimaging research; we briefly address this issue toward the end of our rejoinder.

}, keywords = {Artifacts, Brain, Computer Simulation, Humans, Image Interpretation, Computer-Assisted, Meta-Analysis as Topic}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2011.11.027}, author = {Lindquist, Martin A and Sobel, Michael E} } @article {810, title = {Combining hidden Markov models for comparing the dynamics of multiple sleep electroencephalograms.}, journal = {Stat Med}, volume = {32}, year = {2013}, month = {2013 Aug 30}, pages = {3342-56}, abstract = {

In this manuscript, we consider methods for the analysis of populations of electroencephalogram signals during sleep for the study of sleep disorders using hidden Markov models (HMMs). Notably, we propose an easily implemented method for simultaneously modeling multiple time series that involve large amounts of data. We apply these methods to study sleep-disordered breathing (SDB) in the Sleep Heart Health Study (SHHS), a landmark study of SDB and cardiovascular consequences. We use the entire, longitudinally collected, SHHS cohort to develop HMM population parameters, which we then apply to obtain subject-specific Markovian predictions. From these predictions, we create several indices of interest, such as transition frequencies between latent states. Our HMM analysis of electroencephalogram signals uncovers interesting findings regarding differences in brain activity during sleep between those with and without SDB. These findings include stability of the percent time spent in HMM latent states across matched diseased and non-diseased groups and differences in the rate of transitioning.

}, keywords = {Data Interpretation, Statistical, Electroencephalography, Female, Humans, Longitudinal Studies, Male, Markov Chains, Middle Aged, Models, Statistical, Sleep Apnea Syndromes}, issn = {1097-0258}, doi = {10.1002/sim.5747}, author = {Langrock, Roland and Swihart, Bruce J and Caffo, Brian S and Punjabi, Naresh M and Crainiceanu, Ciprian M} } @article {823, title = {Comparison of total hospital-acquired bloodstream infections to central line-associated bloodstream infections and implications for outcome measures in infection control.}, journal = {Infect Control Hosp Epidemiol}, volume = {34}, year = {2013}, month = {2013 Sep}, pages = {984-6}, abstract = {

The validity of the central line-associated bloodstream infection (CLABSI) measure is compromised by subjectivity. We observed significant decreases in both CLABSIs and total hospital-acquired bloodstream infections (BSIs) following a CLABSI prevention intervention in adult intensive care units. Total hospital-acquired BSIs could be explored as an adjunct, objective CLABSI measure.

}, keywords = {Adult, Catheter-Related Infections, Catheterization, Central Venous, Cross Infection, Humans, Intensive Care Units, Longitudinal Studies, Tertiary Care Centers}, issn = {1559-6834}, doi = {10.1086/671730}, author = {Leekha, Surbhi and Li, Shanshan and Thom, Kerri A and Preas, Michael Anne and Caffo, Brian S and Morgan, Daniel J and Harris, Anthony D} } @article {824, title = {A decision-theory approach to interpretable set analysis for high-dimensional data.}, journal = {Biometrics}, volume = {69}, year = {2013}, month = {2013 Sep}, pages = {614-23}, abstract = {

A key problem in high-dimensional significance analysis is to find pre-defined sets that show enrichment for a statistical signal of interest; the classic example is the enrichment of gene sets for differentially expressed genes. Here, we propose a new decision-theory approach to the analysis of gene sets which focuses on estimating the fraction of non-null variables in a set. We introduce the idea of "atoms," non-overlapping sets based on the original pre-defined set annotations. Our approach focuses on finding the union of atoms that minimizes a weighted average of the number of false discoveries and missed discoveries. We introduce a new false discovery rate for sets, called the atomic false discovery rate (afdr), and prove that the optimal estimator in our decision-theory framework is to threshold the afdr. These results provide a coherent and interpretable framework for the analysis of sets that addresses the key issues of overlapping annotations and difficulty in interpreting p values in both competitive and self-contained tests. We illustrate our method and compare it to a popular existing method using simulated examples, as well as gene-set and brain ROI data analyses.

}, keywords = {Algorithms, Bayes Theorem, Biometry, Brain, Computer Simulation, Data Interpretation, Statistical, Decision Theory, Functional Neuroimaging, Gene Expression Profiling, Genomics, Humans, Magnetic Resonance Imaging, Models, Statistical, Oligonucleotide Array Sequence Analysis}, issn = {1541-0420}, doi = {10.1111/biom.12060}, author = {Boca, Simina M and Bravo, H{\'e}ctor C{\'e}orrada and Caffo, Brian and Leek, Jeffrey T and Parmigiani, Giovanni} } @article {838, title = {Detecting functional connectivity change points for single-subject fMRI data.}, journal = {Front Comput Neurosci}, volume = {7}, year = {2013}, month = {2013}, pages = {143}, abstract = {

Recently in functional magnetic resonance imaging (fMRI) studies there has been an increased interest in understanding the dynamic manner in which brain regions communicate with one another, as subjects perform a set of experimental tasks or as their psychological state changes. Dynamic Connectivity Regression (DCR) is a data-driven technique used for detecting temporal change points in functional connectivity between brain regions where the number and location of the change points are unknown a priori. After finding the change points, DCR estimates a graph or set of relationships between the brain regions for data that falls between pairs of change points. In previous work, the method was predominantly validated using multi-subject data. In this paper, we concentrate on single-subject data and introduce a new DCR algorithm. The new algorithm increases accuracy for individual subject data with a small number of observations and reduces the number of false positives in the estimated undirected graphs. We also introduce a new Likelihood Ratio test for comparing sparse graphs across (or within) subjects; thus allowing us to determine whether data should be combined across subjects. We perform an extensive simulation analysis on vector autoregression (VAR) data as well as to an fMRI data set from a study (n = 23) of a state anxiety induction using a socially evaluative threat challenge. The focus on single-subject data allows us to study the variation between individuals and may provide us with a deeper knowledge of the workings of the brain.

}, issn = {1662-5188}, doi = {10.3389/fncom.2013.00143}, author = {Cribben, Ivor and Wager, Tor D and Lindquist, Martin A} } @article {839, title = {An fMRI-based neurologic signature of physical pain.}, journal = {N Engl J Med}, volume = {368}, year = {2013}, month = {2013 Apr 11}, pages = {1388-97}, abstract = {

BACKGROUND: Persistent pain is measured by means of self-report, the sole reliance on which hampers diagnosis and treatment. Functional magnetic resonance imaging (fMRI) holds promise for identifying objective measures of pain, but brain measures that are sensitive and specific to physical pain have not yet been identified.

METHODS: In four studies involving a total of 114 participants, we developed an fMRI-based measure that predicts pain intensity at the level of the individual person. In study 1, we used machine-learning analyses to identify a pattern of fMRI activity across brain regions--a neurologic signature--that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other regions. In study 2, we tested the sensitivity and specificity of the signature to pain versus warmth in a new sample. In study 3, we assessed specificity relative to social pain, which activates many of the same brain regions as physical pain. In study 4, we assessed the responsiveness of the measure to the analgesic agent remifentanil.

RESULTS: In study 1, the neurologic signature showed sensitivity and specificity of 94\% or more (95\% confidence interval [CI], 89 to 98) in discriminating painful heat from nonpainful warmth, pain anticipation, and pain recall. In study 2, the signature discriminated between painful heat and nonpainful warmth with 93\% sensitivity and specificity (95\% CI, 84 to 100). In study 3, it discriminated between physical pain and social pain with 85\% sensitivity (95\% CI, 76 to 94) and 73\% specificity (95\% CI, 61 to 84) and with 95\% sensitivity and specificity in a forced-choice test of which of two conditions was more painful. In study 4, the strength of the signature response was substantially reduced when remifentanil was administered.

CONCLUSIONS: It is possible to use fMRI to assess pain elicited by noxious heat in healthy persons. Future studies are needed to assess whether the signature predicts clinical pain. (Funded by the National Institute on Drug Abuse and others.).

}, keywords = {Adult, Analgesics, Opioid, Artificial Intelligence, Brain, brain mapping, Female, Hot Temperature, Humans, Magnetic Resonance Imaging, Male, Pain, Pain Measurement, Piperidines, ROC Curve, Sensitivity and Specificity, Young Adult}, issn = {1533-4406}, doi = {10.1056/NEJMoa1204471}, author = {Wager, Tor D and Atlas, Lauren Y and Lindquist, Martin A and Roy, Mathieu and Woo, Choong-Wan and Kross, Ethan} } @article {809, title = {In vivo identification of morphologic retinal abnormalities in neuromyelitis optica.}, journal = {Neurology}, volume = {80}, year = {2013}, month = {2013 Apr 9}, pages = {1406-14}, abstract = {

OBJECTIVE: To assess eyes with neuromyelitis optica (NMO) for morphologic retinal abnormalities utilizing high-definition optical coherence tomography (OCT) imaging.

METHODS: In this cross-sectional study, 39 patients with NMO spectrum disorders and 39 age- and sex-matched healthy controls underwent spectral-domain OCT and visual function testing.

RESULTS: Microcystic macular edema (MME) of the inner nuclear layer (INL) was identified in 10 of 39 patients (26\%) and was exclusively found in eyes with a history of optic neuritis (ON). MME eyes had lower high- and low-contrast letter-acuity scores (100\%: p = 0.002; 2.5\%: p = 0.002; 1.25\%: p = 0.004), lower peripapillary retinal nerve fiber layer (RNFL) thickness (p = 0.04), lower macular RNFL thickness (p = 0.004), lower ganglion cell layer + inner plexiform layer (GCIP) thickness (p = 0.007), higher INL thickness (p < 0.001), and a greater number of ON episodes (p = 0.008) relative to non-MME eyes with a history of ON. After adjusting for history of multiple ON episodes, these findings remained significant for macular-RNFL thickness (p = 0.03), INL thickness (p < 0.001), and 100\% and 2.5\% contrast letter-acuity scores (p = 0.008 and p = 0.03, respectively). NMO spectrum eyes without ON history had lower macular RNFL thickness (p = 0.003), GCIP thickness (p = 0.002), outer nuclear layer thickness (p = 0.02), and low-contrast letter-acuity scores (2.5\%: p = 0.03; 1.25\%: p = 0.002) compared to healthy controls.

CONCLUSIONS: We have identified a pattern of retinal morphologic abnormalities in NMO that is associated with severe retinal axonal and neuronal loss and corresponding visual disability. MME may contribute to poor visual outcomes following NMO-associated ON or alternatively represent a marker of ON severity. Additionally, our results support that subclinical involvement of the anterior visual pathway may occur in NMO spectrum disorders.

}, keywords = {Adolescent, Adult, Aged, Aquaporin 4, Autoantibodies, Case-Control Studies, Chi-Square Distribution, Female, Humans, Macular Edema, Male, Middle Aged, Nerve Fibers, Neuromyelitis Optica, Retina, Tomography, Optical Coherence, Vision Tests, Visual Acuity, Young Adult}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31828c2f7a}, author = {Sotirchos, Elias S and Saidha, Shiv and Byraiah, Gita and Mealy, Maureen A and Ibrahim, Mohamed A and Sepah, Yasir Jamal and Newsome, Scott D and Ratchford, John N and Frohman, Elliot M and Balcer, Laura J and Crainiceanu, Ciprian M and Nguyen, Quan Dong and Levy, Michael and Calabresi, Peter A} } @article {808, title = {Ironing out the statistical wrinkles in "ten ironic rules".}, journal = {Neuroimage}, volume = {81}, year = {2013}, month = {2013 Nov 1}, pages = {499-502}, abstract = {

The article "Ten ironic rules for non-statistical reviewers" (Friston, 2012) shares some commonly heard frustrations about the peer-review process that all researchers can identify with. Though we found the article amusing, we have some concerns about its description of a number of statistical issues. In this commentary we address these issues, as well as the premise of the article.

}, keywords = {Neuroimaging, Peer Review, Research, Research Design, Statistics as Topic}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2013.02.056}, author = {Lindquist, Martin A and Caffo, Brian and Crainiceanu, Ciprian} } @article {825, title = {Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.}, journal = {AIDS Res Hum Retroviruses}, volume = {29}, year = {2013}, month = {2013 Nov}, pages = {1487-95}, abstract = {

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [(99m)Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other enemas (p<0.01). Colon biopsies also showed that only the hyperosmolar enema caused sloughing of the colonic epithelium (p<0.05). In permeability testing, the hypoosmolar enema had higher plasma (99m)Tc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

}, keywords = {Anti-Infective Agents, Biopsy, Colon, Sigmoid, Enema, HIV Infections, Humans, Intestinal Mucosa, Male, Patient Acceptance of Health Care, Solutions, Tomography, Emission-Computed, Single-Photon}, issn = {1931-8405}, doi = {10.1089/AID.2013.0189}, author = {Leyva, Francisco J and Bakshi, Rahul P and Fuchs, Edward J and Li, Liye and Caffo, Brian S and Goldsmith, Arthur J and Ventuneac, Ana and Carballo-Di{\'e}guez, Alex and Du, Yong and Leal, Jeffrey P and Lee, Linda A and Torbenson, Michael S and Hendrix, Craig W} } @article {803, title = {Quantifying the reliability of image replication studies: the image intraclass correlation coefficient (I2C2).}, journal = {Cogn Affect Behav Neurosci}, volume = {13}, year = {2013}, month = {2013 Dec}, pages = {714-24}, abstract = {

This article proposes the image intraclass correlation (I2C2) coefficient as a global measure of reliability for imaging studies. The I2C2 generalizes the classic intraclass correlation (ICC) coefficient to the case when the data of interest are images, thereby providing a measure that is both intuitive and convenient. Drawing a connection with classical measurement error models for replication experiments, the I2C2 can be computed quickly, even in high-dimensional imaging studies. A nonparametric bootstrap procedure is introduced to quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo permutation is utilized to test reproducibility versus a zero I2C2, representing complete lack of reproducibility. Methodologies are applied to three replication studies arising from different brain imaging modalities and settings: regional analysis of volumes in normalized space imaging for characterizing brain morphology, seed-voxel brain activation maps based on resting-state functional magnetic resonance imaging (fMRI), and fractional anisotropy in an area surrounding the corpus callosum via diffusion tensor imaging. Notably, resting-state fMRI brain activation maps are found to have low reliability, ranging from .2 to .4. Software and data are available to provide easy access to the proposed methods.

}, keywords = {Adult, Brain, brain mapping, Computer Simulation, Female, Humans, Male, Models, Biological, Neuroimaging, Reproducibility of Results, Statistics as Topic}, issn = {1531-135X}, doi = {10.3758/s13415-013-0196-0}, author = {Shou, H and Eloyan, A and Lee, S and Zipunnikov, V and Crainiceanu, A N and Nebel, N B and Caffo, B and Lindquist, M A and Crainiceanu, C M} } @article {827, title = {Analysis of group ICA-based connectivity measures from fMRI: application to Alzheimer{\textquoteright}s disease.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e49340}, abstract = {

Functional magnetic resonance imaging (fMRI) is a powerful tool for the in vivo study of the pathophysiology of brain disorders and disease. In this manuscript, we propose an analysis stream for fMRI functional connectivity data and apply it to a novel study of Alzheimer{\textquoteright}s disease. In the first stage, spatial independent component analysis is applied to group fMRI data to obtain common brain networks (spatial maps) and subject-specific mixing matrices (time courses). In the second stage, functional principal component analysis is utilized to decompose the mixing matrices into population-level eigenvectors and subject-specific loadings. Inference is performed using permutation-based exact logistic regression for matched pairs data. The method is applied to a novel fMRI study of Alzheimer{\textquoteright}s disease risk under a verbal paired associates task. We found empirical evidence of alternative ICA-based metrics of connectivity when comparing subjects evidencing mild cognitive impairment relative to carefully matched controls.

}, keywords = {Aged, Algorithms, Alzheimer Disease, Brain, brain mapping, Case-Control Studies, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Mild Cognitive Impairment, Nerve Net, Principal Component Analysis, Task Performance and Analysis, Time Factors}, issn = {1932-6203}, doi = {10.1371/journal.pone.0049340}, author = {Li, Shanshan and Eloyan, Ani and Joel, Suresh and Mostofsky, Stewart and Pekar, James and Bassett, Susan Spear and Caffo, Brian} } @article {calSimex, title = {Assessment of bias in experimentally measured diffusion tensor imaging parameters using SIMEX}, journal = {Accepted in Magnetic Resonance in Medicine}, year = {2012}, author = {Lauzon, C and Crainiceanu, C and Caffo, B and Landman, B} } @article {landmanb, title = {Biological parametric mapping accounting for random regressors with regression calibration and model II regression}, journal = {Accepted in Neuroimage}, year = {2012}, author = {Yang, X and Lauzon, C and Crainiceanu, C and Caffo, B and Resnick, S and Landman, B} } @article {LS11b, title = {Cloak and DAG: A response to the comments on our comment}, journal = {NeuroImage, to appear}, year = {2012}, issn = {1053-8119}, doi = {10.1016/j.neuroimage.2011.11.027}, url = {http://www.sciencedirect.com/science/article/pii/S1053811911013085}, author = {Lindquist, Martin A and Sobel, M.E.} } @article {841, title = {Dissociable influences of opiates and expectations on pain.}, journal = {J Neurosci}, volume = {32}, year = {2012}, month = {2012 Jun 6}, pages = {8053-64}, abstract = {

Placebo treatments and opiate drugs are thought to have common effects on the opioid system and pain-related brain processes. This has created excitement about the potential for expectations to modulate drug effects themselves. If drug effects differ as a function of belief, this would challenge the assumptions underlying the standard clinical trial. We conducted two studies to directly examine the relationship between expectations and opioid analgesia. We administered the opioid agonist remifentanil to human subjects during experimental thermal pain and manipulated participants{\textquoteright} knowledge of drug delivery using an open-hidden design. This allowed us to test drug effects, expectancy (knowledge) effects, and their interactions on pain reports and pain-related responses in the brain. Remifentanil and expectancy both reduced pain, but drug effects on pain reports and fMRI activity did not interact with expectancy. Regions associated with pain processing showed drug-induced modulation during both Open and Hidden conditions, with no differences in drug effects as a function of expectation. Instead, expectancy modulated activity in frontal cortex, with a separable time course from drug effects. These findings reveal that opiates and placebo treatments both influence clinically relevant outcomes and operate without mutual interference.

}, keywords = {Analgesics, Opioid, Anticipation, Psychological, Behavior, brain mapping, Dose-Response Relationship, Drug, Female, Hemodynamics, Hot Temperature, Humans, Image Processing, Computer-Assisted, Injections, Intravenous, Linear Models, Magnetic Resonance Imaging, Male, Pain, Pain Measurement, Piperidines, Young Adult}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0383-12.2012}, author = {Atlas, Lauren Y and Whittington, Robert A and Lindquist, Martin A and Wielgosz, Joe and Sonty, Nomita and Wager, Tor D} } @article {nicole, title = {Distribution of cell-free and cell-associated HIV surrogates in the female genital tract following simulated vaginal intercourse}, journal = {Appeared online in the Journal of Infectious Diseases}, year = {2012}, author = {Louissaint, N and Nimmagadda, S and Bakshi, R and Du, Y and Macura, K and King, K and Wahl, R and Goldsmith, J and Caffo, B and Cao, Y and Anderson, J and Fuchs, E and Hendrix, C} } @article {cribben2012dynamic, title = {Dynamic connectivity regression: Determining state-related changes in brain connectivity}, journal = {NeuroImage}, year = {2012}, publisher = {Elsevier}, author = {Cribben, Ivor and Haraldsdottir, Ragnheidur and Atlas, Lauren Y and Wager, Tor D and Lindquist, Martin A} } @article {842, title = {Dynamic connectivity regression: determining state-related changes in brain connectivity.}, journal = {Neuroimage}, volume = {61}, year = {2012}, month = {2012 Jul 16}, pages = {907-20}, abstract = {

Most statistical analyses of fMRI data assume that the nature, timing and duration of the psychological processes being studied are known. However, often it is hard to specify this information a priori. In this work we introduce a data-driven technique for partitioning the experimental time course into distinct temporal intervals with different multivariate functional connectivity patterns between a set of regions of interest (ROIs). The technique, called Dynamic Connectivity Regression (DCR), detects temporal change points in functional connectivity and estimates a graph, or set of relationships between ROIs, for data in the temporal partition that falls between pairs of change points. Hence, DCR allows for estimation of both the time of change in connectivity and the connectivity graph for each partition, without requiring prior knowledge of the nature of the experimental design. Permutation and bootstrapping methods are used to perform inference on the change points. The method is applied to various simulated data sets as well as to an fMRI data set from a study (N=26) of a state anxiety induction using a socially evaluative threat challenge. The results illustrate the method{\textquoteright}s ability to observe how the networks between different brain regions changed with subjects{\textquoteright} emotional state.

}, keywords = {Algorithms, Brain, brain mapping, Computer Simulation, Emotions, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Neural Pathways}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2012.03.070}, author = {Cribben, Ivor and Haraldsdottir, Ragnheidur and Atlas, Lauren Y and Wager, Tor D and Lindquist, Martin A} } @article {lindquist2012estimating, title = {Estimating and testing variance components in a multi-level GLM}, journal = {Neuroimage}, volume = {59}, number = {1}, year = {2012}, pages = {490{\textendash}501}, publisher = {Elsevier}, author = {Lindquist, Martin A and Spicer, Julie and Asllani, Iris and Wager, Tor D} } @article {844, title = {Estimating and testing variance components in a multi-level GLM.}, journal = {Neuroimage}, volume = {59}, year = {2012}, month = {2012 Jan 2}, pages = {490-501}, abstract = {

Most analysis of multi-subject fMRI data is concerned with determining whether there exists a significant population-wide {\textquoteright}activation{\textquoteright} in a comparison between two or more conditions. This is typically assessed by testing the average value of a contrast of parameter estimates (COPE) against zero in a general linear model (GLM) analysis. However, important information can also be obtained by testing whether there exist significant individual differences in effect magnitude between subjects, i.e. whether the variance of a COPE is significantly different from zero. Intuitively, such a test amounts to testing whether inter-individual differences are larger than would be expected given the within-subject error variance. We compare several methods for estimating variance components, including a) a na{\"\i}ve estimate using ordinary least squares (OLS); b) linear mixed effects in R (LMER); c) a novel Matlab implementation of iterative generalized least squares (IGLS) and its restricted maximum likelihood variant (RIGLS). All methods produced reasonable estimates of within- and between-subject variance components, with IGLS providing an attractive balance between sensitivity and appropriate control of false positives. Finally, we use the IGLS method to estimate inter-subject variance in a perfusion fMRI study (N=18) of social evaluative threat, and show evidence for significant inter-individual differences in ventromedial prefrontal cortex (VMPFC), amygdala, hippocampus and medial temporal lobes, insula, and brainstem, with predicted inverse coupling between VMPFC and the midbrain periaqueductal gray only when high inter-individual variance was used to define the seed for functional connectivity analyses. In sum, tests of variance provides a way of selecting regions that show significant inter-individual variability for subsequent analyses that attempt to explain those individual differences.

}, keywords = {Brain, brain mapping, Humans, Image Interpretation, Computer-Assisted, Linear Models, Magnetic Resonance Imaging, Models, Neurological, Sensitivity and Specificity}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2011.07.077}, author = {Lindquist, Martin A and Spicer, Julie and Asllani, Iris and Wager, Tor D} } @article {lindquist12, title = {Functional causal mediation analysis with an application to brain connectivity}, journal = {Journal of the American Statistical Association, to appear.}, year = {2012}, author = {Lindquist, Martin A} } @article {840, title = {Functional Causal Mediation Analysis With an Application to Brain Connectivity.}, journal = {J Am Stat Assoc}, volume = {107}, year = {2012}, month = {2012 Dec 21}, pages = {1297-1309}, abstract = {

Mediation analysis is often used in the behavioral sciences to investigate the role of intermediate variables that lie on the causal path between a randomized treatment and an outcome variable. Typically, mediation is assessed using structural equation models (SEMs), with model coefficients interpreted as causal effects. In this article, we present an extension of SEMs to the functional data analysis (FDA) setting that allows the mediating variable to be a continuous function rather than a single scalar measure, thus providing the opportunity to study the functional effects of the mediator on the outcome. We provide sufficient conditions for identifying the average causal effects of the functional mediators using the extended SEM, as well as weaker conditions under which an instrumental variable estimand may be interpreted as an effect. The method is applied to data from a functional magnetic resonance imaging (fMRI) study of thermal pain that sought to determine whether activation in certain brain regions mediated the effect of applied temperature on self-reported pain. Our approach provides valuable information about the timing of the mediating effect that is not readily available when using the standard nonfunctional approach. To the best of our knowledge, this work provides the first application of causal inference to the FDA framework.

}, issn = {0162-1459}, doi = {10.1080/01621459.2012.695640}, author = {Lindquist, Martin A} } @article {pmid22006982, title = {Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis}, journal = {Brain}, volume = {135}, number = {Pt 2}, year = {2012}, month = {Feb}, pages = {521{\textendash}533}, author = {Syc, S. B. and Saidha, S. and Newsome, S and Ratchford, J and Levy, M. and Ford, E. and Crainiceanu, C and Durbin, M. K. and Oakley, J. D. and Meyer, S. A. and Frohman, E. M. and Calabresi, P} } @article {rectalab, title = {Quantification of the spatial distribution of rectally-applied surrogates for microbicide and semen in colon with SPECT imaging}, journal = {Accepted in the British Journal of Clinical Pharmacology}, year = {2012}, author = {Cao, Y and Caffo, B and Fuchs, E and Lee, L and Du, Y and Li, L and Bakshi, R and Khan, W and Wahl, R and Grohskopf, L and Hendrix, C} } @article {832, title = {Towards Automatic Quantitative Quality Control for MRI.}, journal = {Proc Soc Photo Opt Instrum Eng}, volume = {8314}, year = {2012}, month = {2012 Feb 23}, abstract = {

Quality and consistency of clinical and research data collected from Magnetic Resonance Imaging (MRI) scanners may become suspect due to a wide variety of common factors including, experimental changes, hardware degradation, hardware replacement, software updates, personnel changes, and observed imaging artifacts. Standard practice limits quality analysis to visual assessment by a researcher/clinician or a quantitative quality control based upon phantoms which may not be timely, cannot account for differing experimental protocol (e.g. gradient timings and strengths), and may not be pertinent to the data or experimental question at hand. This paper presents a parallel processing pipeline developed towards experiment specific automatic quantitative quality control of MRI data using diffusion tensor imaging (DTI) as an experimental test case. The pipeline consists of automatic identification of DTI scans run on the MRI scanner, calculation of DTI contrasts from the data, implementation of modern statistical methods (wild bootstrap and SIMEX) to assess variance and bias in DTI contrasts, and quality assessment via power calculations and normative values. For this pipeline, a DTI specific power calculation analysis is developed as well as the first incorporation of bias estimates in DTI data to improve statistical analysis.

}, issn = {1018-4732}, doi = {10.1117/12.910819}, author = {Lauzon, Carolyn B and Caffo, Brian C and Landman, Bennett A} } @article {pmid21995019, title = {Assessment of bias for MRI diffusion tensor imaging using SIMEX}, journal = {Med Image Comput Comput Assist Interv}, volume = {14}, number = {Pt 2}, year = {2011}, pages = {107{\textendash}115}, author = {Lauzon, C and Asman, A. J. and Crainiceanu, C and Caffo, B and Landman, B} } @article {li3, title = {Comparison of proportions for composite endpoints with missing components}, journal = {Journal of Biopharmaceutical Statistics, NIHMSID: 316386}, volume = {21}, year = {2011}, pages = {271{\textendash}281}, author = {Li, X and Caffo, B} } @article {lewis2011differential, title = {Differential involvement of striato-and cerebello-thalamo-cortical pathways in tremor-and akinetic/rigid-predominant Parkinson{\textquoteright}s disease}, journal = {Neuroscience}, year = {2011}, publisher = {Elsevier}, author = {Lewis, M.M. and Du, G. and Sen, S. and Kawaguchi, A. and Truong, Y. and Lee, S. and Mailman, R.B. and Huang, X.} } @article {nicole2, title = {Distribution of Cell-free and Cell-associated HIV surrogates in the Colon Following Simulated Receptive Anal Intercourse in Healthy Men}, journal = {Journal of Acquired Immune Defficiency Syndromes, Basic and Translational Science}, volume = {59}, number = {1}, year = {2011}, pages = {10{\textendash}17}, author = {Louissaint, N and Nimmagadda, S and Fuchs, E and Bashki, R and Cao, Y and Lee, L and Goldsmith, J and Caffo, B and Du, Y and King, K and Menendez, F and Torbenson, M and Hendrix, C} } @article {LS11a, title = {Graphical models, potential outcomes and causal inference: Comment on Ramsey, Spirtes and Glymour}, journal = {NeuroImage}, volume = {57}, year = {2011}, pages = {334-336}, issn = {1053-8119}, doi = {10.1016/j.neuroimage.2010.10.020}, url = {http://www.sciencedirect.com/science/article/pii/S1053811910013121}, author = {Lindquist, Martin A and Sobel, M.E.} } @article {845, title = {Graphical models, potential outcomes and causal inference: comment on Ramsey, Spirtes and Glymour.}, journal = {Neuroimage}, volume = {57}, year = {2011}, month = {2011 Jul 15}, pages = {334-6}, abstract = {

Ramsey, Spirtes and Glymour (RSG) critique a method proposed by Neumann et al. (2010) for the discovery of functional networks from fMRI meta-analysis data. We concur with this critique, but are unconvinced that directed graphical models (DGMs) are generally useful for estimating causal effects. We express our reservations using the "potential outcomes" framework for causal inference widely used in statistics.

}, keywords = {Artifacts, Brain, Computer Simulation, Humans, Image Interpretation, Computer-Assisted, Meta-Analysis as Topic}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2010.10.020}, author = {Lindquist, Martin A and Sobel, Michael E} } @article {lee2011independent, title = {Independent Component Analysis Involving Autocorrelated Sources With an Application to Functional Magnetic Resonance Imaging}, journal = {Journal of the American Statistical Association}, volume = {106}, number = {495}, year = {2011}, pages = {1009{\textendash}1024}, publisher = {ASA}, author = {Lee, S. and Shen, H. and Truong, Y. and Lewis, M. and Huang, X.} } @article {AJT:AJT3735, title = {MELD Exceptions and Rates of Waiting List Outcomes}, journal = {American Journal of Transplantation}, volume = {11}, number = {11}, year = {2011}, pages = {2362{\textendash}2371}, publisher = {Blackwell Publishing Inc}, keywords = {Liver transplantation, MELD score, organ allocation}, issn = {1600-6143}, doi = {10.1111/j.1600-6143.2011.03735.x}, url = {http://dx.doi.org/10.1111/j.1600-6143.2011.03735.x}, author = {Massie, A and Caffo, B and Gentry, S and Hall, E and Axelrod, D and Lentine, K and Schnitzler, M and Gheorghian, A and Salvalaggio, P and Segev, D} } @article {doi:10.1198/jasa.2011.ap10089, title = {Population value decomposition, a framework for the analysis of image populations}, journal = {Journal of the American Statistical Association, with discussion and rejoinder}, volume = {106}, number = {495}, year = {2011}, pages = {775-790}, doi = {10.1198/jasa.2011.ap10089}, url = {http://pubs.amstat.org/doi/abs/10.1198/jasa.2011.ap10089}, author = {Crainiceanu, C and Caffo, B and Luo, S and Zipunnikov, V. and Punjabi, N} } @article {nazarian2011AI, title = {Prospective study to assess the safety of a protocol for magnetic resonance imaging of patients with implanted cardiac devices}, journal = {Annals of Interal Medicine}, volume = {155}, number = {7}, year = {2011}, pages = {415{\textendash}424}, publisher = {American College of Physicians}, author = {Nazarian, S and Hansford, R and Roguin, A and Goldsher, D and Zviman, M and Lardo, A and Caffo, B and Frick, K and Kraut, M and Kamel, I and Ihab, R and Calkins, H and Berger, R and Bluemke, D and Halperin, H} } @article {atlas, title = {Brain mediators of predictive cue effects on perceived pain}, journal = {J Neurosci}, volume = {30}, year = {2010}, pages = {12964-77}, author = {Atlas, L.Y. and Bolger, N. and Lindquist, Martin A and Wager, T.D.} } @article {846, title = {Brain mediators of predictive cue effects on perceived pain.}, journal = {J Neurosci}, volume = {30}, year = {2010}, month = {2010 Sep 29}, pages = {12964-77}, abstract = {

Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for barely painful or highly painful thermal stimulation, and we assessed how cues influenced human subjects{\textquoteright} pain reports and brain responses to matched levels of noxious heat using functional magnetic resonance imaging. We used multilevel mediation analysis to identify brain regions that (1) are modulated by predictive cues, (2) predict trial-to-trial variations in pain reports, and (3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pretask expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing.

}, keywords = {Adult, Brain, Cognition, Cues, Female, Hot Temperature, Humans, Male, Pain, Pain Threshold, Perception, Physical Stimulation}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0057-10.2010}, author = {Atlas, Lauren Y and Bolger, Niall and Lindquist, Martin A and Wager, Tor D} } @article {kriegeskorte2010everything, title = {Everything you never wanted to know about circular analysis, but were afraid to ask}, journal = {Journal of Cerebral Blood Flow \& Metabolism}, volume = {30}, number = {9}, year = {2010}, pages = {1551{\textendash}1557}, publisher = {Nature Publishing Group}, author = {Kriegeskorte, Nikolaus and Lindquist, Martin A and Nichols, Thomas E and Poldrack, Russell A and Vul, Edward} } @article {847, title = {Everything you never wanted to know about circular analysis, but were afraid to ask.}, journal = {J Cereb Blood Flow Metab}, volume = {30}, year = {2010}, month = {2010 Sep}, pages = {1551-7}, abstract = {

Over the past year, a heated discussion about {\textquoteright}circular{\textquoteright} or {\textquoteright}nonindependent{\textquoteright} analysis in brain imaging has emerged in the literature. An analysis is circular (or nonindependent) if it is based on data that were selected for showing the effect of interest or a related effect. The authors of this paper are researchers who have contributed to the discussion and span a range of viewpoints. To clarify points of agreement and disagreement in the community, we collaboratively assembled a series of questions on circularity herein, to which we provide our individual current answers in }, keywords = {Brain, brain mapping, Data Interpretation, Statistical, Guidelines as Topic, Image Processing, Computer-Assisted, Neurosciences, Publications, Research Design, Selection Bias}, issn = {1559-7016}, doi = {10.1038/jcbfm.2010.86}, author = {Kriegeskorte, Nikolaus and Lindquist, Martin A and Nichols, Thomas E and Poldrack, Russell A and Vul, Edward} } @article {vidwan2010relation, title = {Relation of platelet count to bleeding and vascular complications in patients undergoing coronary angiography}, journal = {The American journal of cardiology}, volume = {105}, number = {9}, year = {2010}, pages = {1219{\textendash}1222}, publisher = {Elsevier}, author = {Vidwan, P. and Lee, S. and Rossi, J.S. and Stouffer, G.A.} } @article {laffan2010utility, title = {Utility of sleep stage transitions in assessing sleep continuity}, journal = {Sleep, PMCID: PMC2982738}, volume = {33}, number = {12}, year = {2010}, pages = {1681}, issn = {0161-8105}, author = {Laffan, A and Caffo, B and Swihart, B and Punjabi, N} } @article {Luo:Crai:Loui:Chat:baye:2009, title = {Bayesian Inference for Smoking Cessation with a Latent Cure State}, journal = {Biometrics}, volume = {65}, number = {3}, year = {2009}, pages = {970{\textendash}978}, keywords = {cure model, MCMC, Mixed-effects model, prediction, Recurrent events, Smoking cessation}, author = {Luo, Sheng and Crainiceanu, C and Louis, Thomas A. and Chatterjee, Nilanjan} } @article {Wager09a, title = {Brain mediators of cardiovascular responses to social threat, Part I: Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity}, journal = {NeuroImage}, volume = {47}, year = {2009}, pages = {821-835}, author = {Wager, T.D. and Waugh, C.E. and Lindquist, Martin A and Noll, D.C. and Fredrickson, B.L. and Taylor, S.F.} } @article {Wager09b, title = {Brain mediators of cardiovascular responses to social threat, Part II: Prefrontal subcortical pathways and relationship with anxiety}, journal = {NeuroImage}, volume = {47}, year = {2009}, pages = {836-851}, author = {Wager, T.D. and van Ast, V. and Davidson, M.L. and Lindquist, Martin A and Ochsner, K.N.} } @article {lindquist2009correlations, title = {Correlations and multiple comparisons in functional imaging: a statistical perspective (Commentary on Vul et al., 2009)}, journal = {Perspectives on Psychological Science}, volume = {4}, number = {3}, year = {2009}, pages = {310{\textendash}313}, publisher = {SAGE Publications}, author = {Lindquist, Martin A and Gelman, Andrew} } @article {lauzon2009easy, title = {Easy Multiplicity Control in Equivalence Testing Using Two One-Sided Tests}, journal = {The American Statistician, PMCID: PMC2800314}, volume = {63}, number = {2}, year = {2009}, pages = {147{\textendash}154}, publisher = {ASA}, author = {Lauzon, C and Caffo, B} } @article {wager2009evaluating, title = {Evaluating the consistency and specificity of neuroimaging data using meta-analysis}, journal = {Neuroimage}, volume = {45}, number = {1}, year = {2009}, pages = {S210{\textendash}S221}, publisher = {Elsevier}, author = {Wager, Tor D and Lindquist, Martin A and Nichols, Thomas E and Kober, Hedy and Van Snellenberg, Jared X} } @article {lindquistJASA09, title = {Logistic Regression with Brownian-like Predictors}, journal = {Journal of the American Statistical Association}, volume = {104}, year = {2009}, pages = {1575-1585}, author = {Lindquist, Martin A and McKeague, I.W.} } @article {lindquist09, title = {Modeling the Hemodynamic Response Function in fMRI: Efficiency, Bias and Mis-modeling}, journal = {NeuroImage}, volume = {45}, year = {2009}, pages = {S187-S198}, author = {Lindquist, Martin A and Loh, J.M. and Atlas, L. and Wager, T.D.} } @article {caffo2009overview, title = {An overview of observational sleep research with application to sleep stage transitioning}, journal = {Chance, PMCID: PMC2800358}, volume = {22}, number = {1}, year = {2009}, pages = {10{\textendash}15}, publisher = {Springer}, author = {Caffo, B and Swihart, B and Crainiceanu, C and Laffan, A and Punjabi, N} } @article {Caff:Swih:Crai:Laff:Punj:an:2009, title = {An Overview of Observational Sleep Research with Application to Sleep State Transitioning}, journal = {Chance}, volume = {22}, number = {1}, year = {2009}, pages = {10{\textendash}15}, author = {Caffo, B and Swihart, B and Crainiceanu, C and Laffan, A and Punjabi, Naresh} } @article {Luo:Crai:Loui:Chat:anal:2008, title = {Analysis of Smoking Cessation Patterns Using a Stochastic Mixed-Effects Model With a Latent Cured State}, journal = {Journal of the American Statistical Association}, volume = {103}, number = {483}, year = {2008}, pages = {1002{\textendash}1013}, keywords = {cure model, Mixed-effects model, Recurrent events, Smoking cessation, stochastic transition model}, author = {Luo, Sheng and Crainiceanu, C and Louis, Thomas A. and Chatterjee, Nilanjan} } @article {grinband2008detection, title = {Detection of time-varying signals in event-related fMRI designs}, journal = {Neuroimage}, volume = {43}, number = {3}, year = {2008}, pages = {509{\textendash}520}, publisher = {Elsevier}, author = {Grinband, Jack and Wager, Tor D and Lindquist, Martin A and Ferrera, Vincent P and Hirsch, Joy} } @article {Wager08, title = {Prefrontal-Subcortical Pathways Mediating Successful Emotion Regulation}, journal = {Neuron}, volume = {59}, year = {2008}, pages = {1037-1050}, author = {Wager, T.D. and Davidson, M.L. and Hughes, B.L. and Lindquist, Martin A and Ochsner, K.N.} } @article {lindquist2008rapid, title = {Rapid three-dimensional functional magnetic resonance imaging}, year = {2008}, author = {Lindquist, Martin A and Zhang, Cun-Hui and Glover, Gary and Shepp, Lawrence} } @article {lindquist08, title = {The Statistical Analysis of fMRI Data}, journal = {Statistical Science}, volume = {23}, year = {2008}, pages = {439{\textendash}464}, author = {Lindquist, Martin A} } @article {wager2007meta, title = {Meta-analysis of functional neuroimaging data: current and future directions}, journal = {Social Cognitive and Affective Neuroscience}, volume = {2}, number = {2}, year = {2007}, pages = {150{\textendash}158}, publisher = {Oxford University Press}, author = {Wager, Tor D and Lindquist, Martin A and Kaplan, Lauren} } @article {lindquist2007modeling, title = {Modeling state-related fMRI activity using change-point theory}, journal = {NeuroImage}, volume = {35}, number = {3}, year = {2007}, pages = {1125{\textendash}1141}, publisher = {Elsevier}, author = {Lindquist, Martin A and Waugh, Christian and Wager, Tor D} } @article {li2007potential, title = {On the potential for ill logic with logically defined outcomes}, journal = {Biostatistics}, volume = {8}, number = {4}, year = {2007}, pages = {800}, author = {Li, X and Caffo, B and Scharfstein, D} } @article {pmid17344421, title = {Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study}, journal = {J. Am. Soc. Nephrol.}, volume = {18}, number = {4}, year = {2007}, month = {Apr}, pages = {1307{\textendash}1315}, author = {Kottgen, A. and Russell, S. D. and Loehr, L. R. and Crainiceanu, C and Rosamond, W. D. and Chang, P. P. and Chambless, L. E. and Coresh, J.} } @article {lindquist07, title = {Validity and Power in Hemodynamic Response Modeling: A comparison study and a new approach}, journal = {Human Brain Mapping}, volume = {28}, year = {2007}, pages = {764-784}, author = {Lindquist, Martin A and Wager, T.D.} } @article {pmid15817517, title = {Electrocorticographic high gamma activity versus electrical cortical stimulation mapping of naming}, journal = {Brain}, volume = {128}, number = {Pt 7}, year = {2005}, month = {Jul}, pages = {1556{\textendash}1570}, author = {Sinai, A. and Bowers, C. W. and Crainiceanu, C and Boatman, D. and Gordon, B. and Lesser, R. P. and Lenz, F. A. and Crone, N.E.} } @article {yacoub2003spin, title = {Spin-echo fMRI in humans using high spatial resolutions and high magnetic fields}, journal = {Magnetic resonance in medicine}, volume = {49}, number = {4}, year = {2003}, pages = {655{\textendash}664}, publisher = {Wiley Online Library}, author = {Yacoub, Essa and Duong, Timothy Q and De Moortele, Van and Lindquist, Martin A and Adriany, Gregor and Kim, Seong-Gi and U{\u g}urbil, K{\^a}mil and Hu, Xiaoping and others} } @article {Greenspan1997, title = {Loss of FHIT expression in cervical carcinoma cell lines and primary tumors.}, journal = {Cancer Research}, volume = {57}, number = {21}, year = {1997}, pages = {4692{\textendash}4698}, publisher = {Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, abstract = {

Allelic deletions involving the short arm of chromosome 3 (3p13-21.1) have been observed frequently in cervical carcinomas. Recently, a candidate tumor suppressor gene, FHIT (Fragile Histidine Triad), was cloned and mapped to this chromosomal region (3p14.2). Abnormal FHIT transcripts have been identified previously in a variety of tumor cell lines and primary carcinomas, although their significance and the molecular mechanisms underlying their origin remain incompletely defined. In addition, integration of human papillomavirus DNA has been identified at a fragile site (FRA3B) within the FHIT locus in cervical cancer. These observations motivated us to evaluate FHIT mRNA and protein expression in cervical cancer cell lines, primary cervical carcinomas, and normal tissues. Transcripts of the expected size and sequence were the predominant species identified by reverse transcription (RT)-PCR in cultured keratinocytes and all normal tissues evaluated. In contrast, aberrant FHIT transcripts were readily demonstrated in 6 of 7 cervical carcinoma cell lines and 17 of 25 (68\%) primary cervical carcinomas. Northern blot analyses demonstrated reduced or absent FHIT expression in the cervical carcinoma cell lines, particularly those with aberrant RT-PCR products. Immunohistochemical analysis of Fhit expression in cervical tissues revealed strong immunoreactivity in nonneoplastic squamous and glandular cervical epithelium and marked reduction or loss of Fhit protein in 25 of 33 (76\%) primary cervical carcinomas. In those cervical cancer cell lines and primary tumors with exclusively aberrant or absent FHIT transcripts by RT-PCR, Fhit protein expression was always markedly reduced or absent. The frequent alterations in FHIT expression in many cervical carcinomas, but not in normal tissues, suggest that FHIT gene alterations may play an important role in cervical tumorigenesis.

}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9354423}, author = {Greenspan, D L and Connolly, D C and Wu, R and Lei, R Y and Vogelstein, Joshua T and Kim, Y T and Mok, J E and Mu{\~n}oz, N and Bosch, F X and Shah, K and Cho, K R} }