@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 {798, title = {Assessing the "physical cliff": detailed quantification of age-related differences in daily patterns of physical activity.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Aug}, pages = {973-9}, abstract = {

BACKGROUND: In spite of evidence that physical activity has beneficial effects on health and age-related functional decline, there is a scarcity of detailed and accurate information on objectively measured daily activity and patterns of such activity in older adults.

METHODS: Participants in the Baltimore Longitudinal Study of Aging (n = 611, 50\% male, mean age 67, range 32-93) wore the Actiheart portable activity monitor for 7 days in the free-living environment. The association between activity and age was modeled using a continuous log-linear regression of activity counts on age with sex, body mass index, employment status, functional performance, and comorbid conditions as covariates.

RESULTS: In the fully adjusted model, continuous analyses demonstrated that overall physical activity counts were 1.3\% lower for each year increase in age. Although there were no differences among morning levels of activity, there was significantly lower afternoon and evening activity in older individuals (p < .01). After adjusting for age, poor functional performance, nonworking status, and higher body mass index were independently associated with less physical activity (p < .001).

CONCLUSIONS: The use of accelerometers to characterize minute-by-minute intensity, cumulative physical activity counts, and daily activity patterns provides detailed data not gathered by traditional subjective methods, particularly at low levels of activity. The findings of a 1.3\% decrease per year in activity from mid-to-late life, and the corresponding drop in afternoon and evening activity, provide new information that may be useful when targeting future interventions. Further, this methodology addresses essential gaps in understanding activity patterns and trends in more sedentary sectors of the population.

}, keywords = {Accelerometry, Adult, Age Factors, Aged, Aged, 80 and over, Employment, Female, Health Behavior, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Motor Activity, Physical Fitness, Sedentary Lifestyle}, issn = {1758-535X}, doi = {10.1093/gerona/glt199}, author = {Schrack, Jennifer A and Zipunnikov, Vadim and Goldsmith, Jeff and Bai, Jiawei and Simonsick, Eleanor M and Crainiceanu, Ciprian and Ferrucci, Luigi} } @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 {833, title = {Cross-sectional and longitudinal association of body mass index and brain volume.}, journal = {Hum Brain Mapp}, volume = {35}, year = {2014}, month = {2014 Jan}, pages = {75-88}, abstract = {

Although a link between body mass index (BMI) and brain volume has been established in several cross-sectional studies, evidence of the association between change in BMI over time and changes in brain structure is limited. Using data from a cohort of 347 former lead workers and community controls with two magnetic resonance imaging scans over a period of ~5 years, we estimated cross-sectional and longitudinal associations of BMI and brain volume using both region of interest (ROI) and voxel-based morphometric (VBM) methods. We found that associations of BMI and brain volume were not significantly different in former lead workers when compared with community controls. In the cross-sectional analysis, higher BMIs were associated with smaller brain volumes in gray matter (GM) using both ROI and VBM approaches. No associations with white matter (WM) were observed. In the longitudinal analysis, higher baseline BMI was associated with greater decline in temporal and occipital GM ROI volumes. Change in BMI over the 5-year period was only associated with change in hippocampal volume and was not associated with change in any of the GM ROIs. Overall, higher BMI was associated with lower GM volume in several ROIs and with declines in volume in temporal and occipital GM over time. These results suggest that sustained high body mass may contribute to progressive temporal and occipital atrophy.

}, keywords = {Aged, Atrophy, Body Mass Index, Brain, Cross-Sectional Studies, Humans, Image Interpretation, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Obesity}, issn = {1097-0193}, doi = {10.1002/hbm.22159}, author = {Bobb, Jennifer F and Schwartz, Brian S and Davatzikos, Christos and Caffo, Brian} } @article {831, title = {Disruption of functional organization within the primary motor cortex in children with autism.}, journal = {Hum Brain Mapp}, volume = {35}, year = {2014}, month = {2014 Feb}, pages = {567-80}, abstract = {

Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left-right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex.

}, keywords = {Adult, Autistic Disorder, brain mapping, Child, Developmental Disabilities, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Motor Cortex, Oxygen, Young Adult}, issn = {1097-0193}, doi = {10.1002/hbm.22188}, author = {Nebel, Mary Beth and Joel, Suresh E and Muschelli, John and Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {794, title = {Estimating energy expenditure from heart rate in older adults: a case for calibration.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e93520}, abstract = {

BACKGROUND: Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear.

OBJECTIVE: To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration.

DESIGN: Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance.

RESULTS: Heart rate and energy expenditure were highly correlated (r=0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. =0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min).

CONCLUSION: These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0093520}, author = {Schrack, Jennifer A and Zipunnikov, Vadim and Goldsmith, Jeff and Bandeen-Roche, Karen and Crainiceanu, Ciprian M and Ferrucci, Luigi} } @article {816, title = {Evidence for Specificity of Motor Impairments in Catching and Balance in Children with Autism.}, journal = {J Autism Dev Disord}, year = {2014}, month = {2014 Sep 18}, abstract = {

To evaluate evidence for motor impairment specificity in autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Children completed performance-based assessment of motor functioning (Movement Assessment Battery for Children: MABC-2). Logistic regression models were used to predict group membership. In the models comparing typically developing and developmental disability (DD), all three MABC subscale scores were significantly negatively associated with having a DD. In the models comparing ADHD and ASD, catching and static balance items were associated with ASD group membership, with a 1 point decrease in performance increasing odds of ASD by 36 and 39~\%, respectively. Impairments in motor skills requiring the coupling of visual and temporal feedback to guide and adjust movement appear specifically deficient in ASD.

}, issn = {1573-3432}, doi = {10.1007/s10803-014-2229-0}, author = {Ament, Katarina and Mejia, Amanda and Buhlman, Rebecca and Erklin, Shannon and Caffo, Brian and Mostofsky, Stewart and Wodka, Ericka} } @article {804, title = {Normalization and extraction of interpretable metrics from raw accelerometry data.}, journal = {Biostatistics}, volume = {15}, year = {2014}, month = {2014 Jan}, pages = {102-16}, abstract = {

We introduce an explicit set of metrics for human activity based on high-density acceleration recordings from a hip-worn tri-axial accelerometer. These metrics are based on two concepts: (i) Time Active, a measure of the length of time when activity is distinguishable from rest and (ii) AI, a measure of the relative amplitude of activity relative to rest. All measurements are normalized (have the same interpretation across subjects and days), easy to explain and implement, and reproducible across platforms and software implementations. Metrics were validated by visual inspection of results and quantitative in-lab replication studies, and by an association study with health outcomes.

}, keywords = {Acceleration, Aged, Baltimore, Cohort Studies, Data Interpretation, Statistical, Female, Humans, Male, Motor Activity}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxt029}, author = {Bai, Jiawei and He, Bing and Shou, Haochang and Zipunnikov, Vadim and Glass, Thomas A and Crainiceanu, Ciprian M} } @article {Bai2014Metrics, title = {Normalization and extraction of interpretable metrics from raw accelerometry data}, journal = {Biostatistics}, volume = {15}, number = {1}, year = {2014}, pages = {102{\textendash}116}, abstract = {

We introduce an explicit set of metrics for human activity based on high-density acceleration recordings from a hip-worn tri-axial accelerometer. These metrics are based on two concepts: (i) Time Active, a measure of the length of time when activity is distinguishable from rest and (ii) AI, a measure of the relative amplitude of activity relative to rest. All measurements are normalized (have the same interpretation across subjects and days), easy to explain and implement, and reproducible across platforms and software implementations. Metrics were validated by visual inspection of results and quantitative in-lab replication studies, and by an association study with health outcomes.

}, keywords = {Activity intensity, Movelets, Movement, Signal processing, Time active, Tri-axial accelerometer}, issn = {14654644}, author = {Bai, Jiawei and He, Bing and Shou, Haochang and Zipunnikov, Vadim and Glass, Thomas A. and Crainiceanu, Ciprian M.} } @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 {818, title = {Reduction of motion-related artifacts in resting state fMRI using aCompCor.}, journal = {Neuroimage}, volume = {96}, year = {2014}, month = {2014 Aug 1}, pages = {22-35}, abstract = {

Recent studies have illustrated that motion-related artifacts remain in resting-state fMRI (rs-fMRI) data even after common corrective processing procedures have been applied, but the extent to which head motion distorts the data may be modulated by the corrective approach taken. We compare two different methods for estimating nuisance signals from tissues not expected to exhibit BOLD fMRI signals of neuronal origin: 1) the more commonly used mean signal method and 2) the principal components analysis approach (aCompCor: Behzadi et al., 2007). Further, we investigate the added benefit of "scrubbing" (Power et al., 2012) following both methods. We demonstrate that the use of aCompCor removes motion artifacts more effectively than tissue-mean signal regression. In addition, inclusion of more components from anatomically defined regions of no interest better mitigates motion-related artifacts and improves the specificity of functional connectivity estimates. While scrubbing further attenuates motion-related artifacts when mean signals are used, scrubbing provides no additional benefit in terms of motion artifact reduction or connectivity specificity when using aCompCor.

}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2014.03.028}, author = {Muschelli, John and Nebel, Mary Beth and Caffo, Brian S and Barber, Anita D and Pekar, James J and Mostofsky, Stewart H} } @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 {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 {829, title = {Developmental changes in within- and between-network connectivity between late childhood and adulthood.}, journal = {Neuropsychologia}, volume = {51}, year = {2013}, month = {2013 Jan}, pages = {156-67}, abstract = {

A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain-behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control.

}, keywords = {Adolescent, Adult, Age Factors, Analysis of Variance, Brain, brain mapping, Child, Child Development, Cognition, Female, Humans, Image Processing, Computer-Assisted, Inhibition (Psychology), Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Oxygen, Reaction Time, Young Adult}, issn = {1873-3514}, doi = {10.1016/j.neuropsychologia.2012.11.011}, author = {Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @article {826, title = {Effects of working memory demand on neural mechanisms of motor response selection and control.}, journal = {J Cogn Neurosci}, volume = {25}, year = {2013}, month = {2013 Aug}, pages = {1235-48}, abstract = {

Inhibitory control commonly recruits a number of frontal regions: pre-supplementary motor area (pre-SMA), frontal eye fields (FEFs), and right-lateralized posterior inferior frontal gyrus (IFG), dorsal anterior insula (DAI), dorsolateral prefrontal cortex (DLPFC), and inferior frontal junction (IFJ). These regions may directly implement inhibitory motor control or may be more generally involved in executive control functions. Two go/no-go tasks were used to distinguish regions specifically recruited for inhibition from those that additionally show increased activity with working memory demand. The pre-SMA and IFG were recruited for inhibition in both tasks and did not have greater activation for working memory demand on no-go trials, consistent with a role in inhibitory control. Activation in pre-SMA also responded to response selection demand and was increased with working memory on go trials specifically. The bilateral FEF and right DAI were commonly active for no-go trials. The FEF was also recruited to a greater degree with working memory demand on go trials and may bias top-down information when stimulus-response mappings change. The DAI, additionally responded to increased working memory demand on both go and no-go trials and may be involved in accessing sustained task information, alerting, or autonomic changes when cognitive demands increase. DLPFC activation was consistent with a role in working memory retrieval on both go and no-go trials. The inferior frontal junction, on the other hand, had greater activation with working memory specifically for no-go trials and may detect salient stimuli when the task requires frequent updating of working memory representations.

}, keywords = {Adult, Brain, brain mapping, Choice Behavior, Female, Humans, Image Processing, Computer-Assisted, Inhibition (Psychology), Magnetic Resonance Imaging, Male, Memory, Short-Term, Motor Activity, Neuropsychological Tests, Oxygen, Reaction Time, Young Adult}, issn = {1530-8898}, doi = {10.1162/jocn_a_00394}, author = {Barber, Anita D and Caffo, Brian S and Pekar, James J and Mostofsky, Stewart H} } @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 {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 {811, title = {Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.}, journal = {JAMA Neurol}, volume = {70}, year = {2013}, month = {2013 Jan}, pages = {34-43}, abstract = {

OBJECTIVE: To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS).

DESIGN: Cross-sectional study.

SETTING: Johns Hopkins University, Baltimore, Maryland.

PARTICIPANTS: A total of 84 patients with MS and 24 healthy control subjects.

MAIN OUTCOME MEASURES: High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes.

RESULTS: Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer+inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P=.01 and P=.04, respectively) and caudate (P=.04 and P=.03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P=.007) and inversely associated with normal-appearing white matter volume (P=.005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.

}, keywords = {Adult, Axons, Caudate Nucleus, Central Nervous System, Cerebral Cortex, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Retina, Retinal Neurons, Tomography, Optical Coherence}, issn = {2168-6157}, doi = {10.1001/jamaneurol.2013.573}, author = {Saidha, Shiv and Sotirchos, Elias S and Oh, Jiwon and Syc, Stephanie B and Seigo, Michaela A and Shiee, Navid and Eckstein, Chistopher and Durbin, Mary K and Oakley, Jonathan D and Meyer, Scott A and Frohman, Teresa C and Newsome, Scott and Ratchford, John N and Balcer, Laura J and Pham, Dzung L and Crainiceanu, Ciprian M and Frohman, Elliot M and Reich, Daniel S and Calabresi, Peter A} } @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 {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 {709, title = {Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study.}, journal = {Lancet Neurol}, volume = {11}, year = {2012}, month = {2012 Nov}, pages = {963-72}, abstract = {

BACKGROUND: Microcystic macular oedema (MMO) of the retinal inner nuclear layer (INL) has been identified in patients with multiple sclerosis (MS) by use of optical coherence tomography (OCT). We aimed to determine whether MMO of the INL, and increased thickness of the INL are associated with disease activity or disability progression.

METHODS: This retrospective study was done at the Johns Hopkins Hospital (Baltimore, MD, USA), between September, 2008, and March, 2012. Patients with MS and healthy controls underwent serial OCT scans and clinical assessments including visual function. OCT scanning, including automated intraretinal layer segmentation, yielded thicknesses of the retinal nerve fibre layer, the ganglion cell layer plus inner plexiform layer, the INL plus outer plexiform layer (the combined thickness of these layers was used as a surrogate measure of INL thickness), and the outer nuclear layer. Patients with MS also underwent annual brain MRI scans. Disability scores were compared with the Wilcoxon rank-sum test. Mixed-effects linear regression was used to compare OCT measures and letter-acuity scores. Logistic regression was used to examine the relations of baseline OCT thicknesses with clinical and radiological parameters.

FINDINGS: 164 patients with MS and 60 healthy controls were assessed. Mean follow-up was 25{\textperiodcentered}8 months (SD 9{\textperiodcentered}1) for patients with MS and 22{\textperiodcentered}4 months (11{\textperiodcentered}4) for healthy controls. Ten (6\%) patients with MS had MMO during at least one study visit; MMO was visible at baseline in four of these patients. Healthy controls did not have MMO. Patients with MS and MMO had higher baseline MS severity scores (median 5{\textperiodcentered}93 [range 2{\textperiodcentered}44-8{\textperiodcentered}91]) than those who did not have MMO at any time during the study (151 patients; 3{\textperiodcentered}81 [0{\textperiodcentered}13-9{\textperiodcentered}47]; p=0{\textperiodcentered}032), although expanded disability status scale (EDSS) scores were not significantly different (5{\textperiodcentered}2 [1{\textperiodcentered}0-6{\textperiodcentered}5] for patients with MS and MMO vs 2{\textperiodcentered}5 [0{\textperiodcentered}0-8{\textperiodcentered}0] for those without MMO; p=0{\textperiodcentered}097). The eyes of patients with MS and MMO (12 eyes) versus those without MMO (302 eyes) had lower letter-acuity scores (100\% contrast, p=0{\textperiodcentered}017; 2{\textperiodcentered}5\% contrast, p=0{\textperiodcentered}031; 1{\textperiodcentered}25\% contrast, p=0{\textperiodcentered}014), and increased INL thicknesses (p=0{\textperiodcentered}003) at baseline. Increased baseline INL thickness in patients with MS was associated with the development of contrast-enhancing lesions (p=0{\textperiodcentered}007), new T2 lesions (p=0{\textperiodcentered}015), EDSS progression (p=0{\textperiodcentered}034), and relapses in patients with relapsing-remitting MS (p=0{\textperiodcentered}008) during the study. MMO was not associated with disease activity during follow-up.

INTERPRETATION: Increased INL thickness on OCT is associated with disease activity in MS. If this finding is confirmed, INL thickness could be a useful predictor of disease progression in patients with MS.

FUNDING: National Multiple Sclerosis Society, National Eye Institute, Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.

}, keywords = {Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Macular Edema, Male, Middle Aged, Multiple Sclerosis, Retina, Retinal Ganglion Cells, Retrospective Studies, Tomography, Optical Coherence}, issn = {1474-4465}, doi = {10.1016/S1474-4422(12)70213-2}, author = {Saidha, Shiv and Sotirchos, Elias S and Ibrahim, Mohamed A and Crainiceanu, Ciprian M and Gelfand, Jeffrey M and Sepah, Yasir J and Ratchford, John N and Oh, Jiwon and Seigo, Michaela A and Newsome, Scott D and Balcer, Laura J and Frohman, Elliot M and Green, Ari J and Nguyen, Quan D and Calabresi, Peter A} } @article {barber, title = {Motor "dexterity"?: evidence that left hemisphere lateralization of motor circuit connectivity is associated with better motor performance in children}, journal = {Cerebral Cortex}, year = {2012}, author = {Barber, A and Srinivasan, P and Joel, S. and Caffo, B and Pekar, J and Mostofsky, S} } @article {BaGoCaGlCr2012, title = {Movelets: A dictionary of movement}, journal = {Electronic Journal of Statistics}, volume = {6}, year = {2012}, pages = {559-578}, issn = {1935-7524}, doi = {10.1214/12-EJS684}, author = {Bai, J and Goldsmith, J and Caffo, B and Glass, T and Crainiceanu, C} } @article {813, title = {Movelets: A dictionary of movement.}, journal = {Electron J Stat}, volume = {6}, year = {2012}, month = {2012}, pages = {559-578}, abstract = {

Recent technological advances provide researchers with a way of gathering real-time information on an individual{\textquoteright}s movement through the use of wearable devices that record acceleration. In this paper, we propose a method for identifying activity types, like walking, standing, and resting, from acceleration data. Our approach decomposes movements into short components called "movelets", and builds a reference for each activity type. Unknown activities are predicted by matching new movelets to the reference. We apply our method to data collected from a single, three-axis accelerometer and focus on activities of interest in studying physical function in elderly populations. An important technical advantage of our methods is that they allow identification of short activities, such as taking two or three steps and then stopping, as well as low frequency rare(compared with the whole time series) activities, such as sitting on a chair. Based on our results we provide simple and actionable recommendations for the design and implementation of large epidemiological studies that could collect accelerometry data for the purpose of predicting the time series of activities and connecting it to health outcomes.

}, issn = {1935-7524}, doi = {10.1214/12-EJS684}, author = {Bai, Jiawei and Goldsmith, Jeff and Caffo, Brian and Glass, Thomas A and Crainiceanu, Ciprian M} } @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 {710, title = {Relationships Between Retinal Axonal and Neuronal Measures and Global Central Nervous System Pathology in Multiple Sclerosis.}, journal = {Arch Neurol}, year = {2012}, month = {2012 Oct 1}, pages = {1-10}, abstract = {

OBJECTIVE To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS). DESIGN Cross-sectional study. SETTING Johns Hopkins University, Baltimore, Maryland. PARTICIPANTS A total of 84 patients with MS and 24 healthy control subjects. MAIN OUTCOME MEASURES High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes. RESULTS Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer\ +\ inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P\ =\ .01 and P\ =\ .04, respectively) and caudate (P\ =\ .04 and P\ =\ .03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P\ =\ .007) and inversely associated with normal-appearing white matter volume (P\ =\ .005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.

}, issn = {1538-3687}, doi = {10.1001/archneurol.2013.573}, author = {Saidha, Shiv and Sotirchos, Elias S and Oh, Jiwon and Syc, Stephanie B and Seigo, Michaela A and Shiee, Navid and Eckstein, Chistopher and Durbin, Mary K and Oakley, Jonathan D and Meyer, Scott A and Frohman, Teresa C and Newsome, Scott and Ratchford, John N and Balcer, Laura J and Pham, Dzung L and Crainiceanu, Ciprian M and Frohman, Elliot M and Reich, Daniel S and Calabresi, Peter A} } @article {shee, title = {Revisiting Brain Atrophy and Its Relationship to Disability in Multiple Sclerosis}, journal = {PLoS ONE}, volume = {7}, number = {5}, year = {2012}, month = {05}, pages = {e37049}, publisher = {Public Library of Science}, doi = {10.1371/journal.pone.0037049}, url = {http://dx.doi.org/10.1371\%2Fjournal.pone.0037049}, author = {Shiee, N and Bazin, P and Zackowski, K and Farrell, S and Harrison, D and Newsome, S and Ratchford, J and Caffo, B and Calabresi, P and Pham, D and Reich, D.} } @article {830, title = {Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives.}, journal = {Bipolar Disord}, volume = {14}, year = {2012}, month = {2012 Dec}, pages = {888-93}, abstract = {

OBJECTIVES: White matter hyperintensities (WMH) are more common in subjects with bipolar disorder (BP) than in healthy subjects (HS). Few studies have examined the effect of the diagnostic type of bipolar illness on WMH burden, and none have approached this question through a direct measurement of the volume of affected white matter in relationship to familiality. In this pilot study, we utilized a volumetric measurement of WMH to investigate the relationship between the total volume of WMH and the familiality and type of BP.

METHODS: Forty-five individuals with bipolar I disorder (BP-I) with psychotic features, BP-I without psychotic features, or bipolar II disorder (BP-II), seven of their unaffected relatives, and 32 HS were recruited for participation. T-2 weighted magnetic resonance imaging scans were obtained on all subjects, and the total volume of all WMH for each subject was measured in cubic centimeters. The significance of difference between groups was tested using ANOVA with post-hoc adjustment for multiple comparisons. Further, we used logistic regression to test for trends between symptom load and total WMH volume.

RESULTS: The mean total volume of WMH in BP-I patients with psychotic features was significantly higher (p < 0.05) than that of HS. Further, we observed a positive linear trend by familiality and type of affectedness when comparing mean total WMH volume of HS, unaffected family members, subjects with BP-II, and BP-I with and without a history of psychosis (p < 0.05).

CONCLUSIONS: Based on a quantitative technique, WMH burden appears to be associated with familiality and type of BP. The significance of these findings remains to be fully elucidated.

}, keywords = {Adult, Analysis of Variance, Bipolar Disorder, Brain, Female, Humans, Image Processing, Computer-Assisted, Leukoencephalopathies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated}, issn = {1399-5618}, doi = {10.1111/bdi.12019}, author = {Tighe, Sarah K and Reading, Sarah A and Rivkin, Paul and Caffo, Brian and Schweizer, Barbara and Pearlson, Godfrey and Potash, James B and Depaulo, J Raymond and Bassett, Susan S} } @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 {reiss2011extracting, title = {Extracting information from functional connectivity maps via function-on-scalar regression}, journal = {NeuroImage}, volume = {56}, number = {1}, year = {2011}, pages = {140{\textendash}148}, author = {Reiss, P.T. and Mennes, M. and Petkova, E. and Huang, L. and Hoptman, M.J. and Biswal, B.B. and Colcombe, S.J. and Zuo, X.N. and Milham, M.P.} } @article {pmid21853058, title = {The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials}, journal = {PLoS ONE}, volume = {6}, number = {8}, year = {2011}, pages = {e22947}, author = {Warner, C. V. and Syc, S. B. and Stankiewicz, A. M. and Hiremath, G. and Farrell, S and Crainiceanu, C and Conger, A. and Frohman, T. C. and Bisker, E. R. and Balcer, L and Frohman, E. M. and Calabresi, P and Saidha, S.} } @article {doi:10.1198/jcgs.2010.10007, title = {Penalized Functional Regression}, journal = {Journal of Computational and Graphical Statistics}, volume = {20}, number = {4}, year = {2011}, pages = {830-851}, doi = {10.1198/jcgs.2010.10007}, url = {http://pubs.amstat.org/doi/abs/10.1198/jcgs.2010.10007}, author = {Goldsmith, J and Bobb, J. and Crainiceanu, C and Caffo, B and Reich, D.} } @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 {hedlin2009covariate, title = {Covariate-adjusted nonparametric analysis of magnetic resonance images using Markov chain Monte Carlo}, journal = {Statistics and its Interface, NIHMSID: 210823}, volume = {3}, number = {1}, year = {2010}, pages = {113-123}, author = {Hedlin, H and Caffo, B and Mahfoud, Z and Bassett, S} } @conference {Knei:Brez:Crai:gene:2010, title = {Generalized Semiparametric Regression with Covariates Measured with Error}, booktitle = {Statistical Modelling and Regression Structures: Festschrift in Honour of Ludwig Fahrmeir}, year = {2010}, pages = {133{\textendash}154}, publisher = {Physica-Verlag Ges.m.b.H}, organization = {Physica-Verlag Ges.m.b.H}, author = {Kneib, Thomas and Brezger, Andreas and Crainiceanu, C}, editor = {Kneib, Thomas and Tutz, Gerhard} } @article {nazarian:qrs, title = {QRS Prolongation in Myotonic Muscular Dystrophy and Diffuse Fibrosis on Cardiac Magnetic Resonance}, journal = {Magnetic Resonance in Medicine, PMCID: PMC3034129}, volume = {64}, number = {1}, year = {2010}, pages = {107{\textendash}114}, author = {Nazarian, S and Bluemke, D and Wagner, K and Zviman, M and Turkbey, E and Caffo, B and Shehata, M and Edwards,D and Butcher, B and Calkins, H and Berger, R and Halperin, H and Tomaselli, G} } @article {boatman, title = {Quantifying Auditory Event-Related Responses in Multichannel Human Intracranial Recordings}, journal = {Invited submission to Frontiers in Computational Neuroscience, PMCID: PMC2859880}, volume = {4}, number = {4}, year = {2010}, pages = {1{\textendash}17}, author = {Boatman-Reich, D and Franaszczuk, Piotr J. and Korzeniewska, A. and Caffo, B and Ritzl, E and Colwell, S and Crone, N} } @article {pmid20227508, title = {Two-stage decompositions for the analysis of functional connectivity for fMRI with application to Alzheimer{\textquoteright}s disease risk}, journal = {Neuroimage}, volume = {51}, number = {3}, year = {2010}, month = {Jul}, pages = {1140{\textendash}1149}, author = {Caffo, B and Crainiceanu, C and Verduzco, G. and Joel, S. and Mostofsky, S and Bassett, S and Pekar, J} } @article {reich2009damage, title = {Damage to the Optic Radiation in Multiple Sclerosis Is Associated With Retinal Injury and Visual Disability}, journal = {Archives of Neurology, PMCID: PMC2784485}, volume = {66}, number = {8}, year = {2009}, pages = {998{\textendash}1006}, publisher = {Am Med Assoc}, author = {Reich, D. and Smith, S and Gordon-Lipkin, E and Ozturk, A and Caffo, B and Balcer, L and Calabresi, P} } @article {yousem2009intelligence, title = {Intelligence and Medial Temporal Lobe Function in Older Adults: A Functional MR Imaging-Based Investigation}, journal = {American Journal of Neuroradiology, PMCID: PMC2843089}, volume = {30}, number = {8}, year = {2009}, pages = {1477{\textendash}1481}, publisher = {Am Soc Neuroradiology}, author = {Yousem, D and Yassa, M and Cristinzio, C and Kusevic, I and Mohamed, M and Caffo, B and Bassett, S} } @article {su2009modified, title = {Modified test statistics by inter-voxel variance shrinkage with an application to fMRI}, journal = {Biostatistics, NIHMSID: 316409}, volume = {10}, number = {2}, year = {2009}, pages = {219-227}, author = {Su, S and Caffo, B and Garrett-Mayer, E and Bassett, S} } @article {bowman2008bayesian, title = {A Bayesian hierarchical framework for spatial modeling of fMRI data}, journal = {NeuroImage, PMCID: PMC2134321}, volume = {39}, number = {1}, year = {2008}, pages = {146{\textendash}156}, publisher = {Elsevier}, author = {Bowman, F and Caffo, B and Bassett, S and Kilts, C} } @article {swihart2008quantitative, title = {Characterizing Sleep Structure Using the Hypnogram}, journal = {Journal of Clinical Sleep Medicine, PMCID: PMC2542492}, volume = {4}, number = {4}, year = {2008}, pages = {349{\textendash}355}, author = {Swihart, B and Caffo, B and Bandeen-Roche, K and Punjabi, N} } @article {redgrave2008differential, title = {Differential brain activation in anorexia nervosa to Fat and Thin words during a Stroop task}, journal = {NeuroReport, PMCID: PMC2891098}, volume = {19}, number = {12}, year = {2008}, pages = {1181{\textendash}1185}, author = {Redgrave, G and Bakker, A and Bello, N and Caffo, B and Coughlin, J and Guarda, A and McEntee, J and Pekar, J and Reinblatt, S and Verduzco, G. and Moran, T} } @article {zhang2008power, title = {Power Spectral Analysis of EEG Activity During Sleep in Cigarette Smokers}, journal = {Chest}, volume = {133}, number = {2}, year = {2008}, pages = {427{\textendash}432}, publisher = {Am Coll Chest Phys}, author = {Zhang, L and Samet, J and Caffo, B and Bankman, I and Punjabi, N} } @article {caffo2007brain, title = {Are Brain Volumes based on Magnetic Resonance Imaging Mediators of the Associations of Cumulative Lead Dose with Cognitive Function?}, journal = {American Journal of Epidemiology}, volume = {167}, number = {4}, year = {2007}, pages = {429{\textendash}437}, publisher = {Oxford Univ Press}, author = {Caffo, B and Chen, S and Stewart, W and Bolla, K and Yousem, D and Davatzikos, C. and Schwartz, B} } @article {schwartz2007relations, title = {Relations of brain volumes with cognitive function in males 45 years and older with past lead exposure}, journal = {Neuroimage, PMCID: PMC2038986}, volume = {37}, number = {2}, year = {2007}, pages = {633{\textendash}641}, publisher = {Elsevier}, author = {Schwartz, B and Chen, S and Caffo, B and Stewart, W and Bolla, K and Yousem, D and Davatzikos, C.} } @article {pmid17646610, title = {Short-term variability in measures of glycemia and implications for the classification of diabetes}, journal = {Arch. Intern. Med.}, volume = {167}, number = {14}, year = {2007}, month = {Jul}, pages = {1545{\textendash}1551}, author = {Selvin, E. and Crainiceanu, C and Brancati, F. L. and Coresh, J.} } @article {bassett2006familial, title = {Familial risk for Alzheimer{\textquoteright}s disease alters fMRI activation patterns}, journal = {Brain, PMCID: PMC2744898}, volume = {129}, number = {5}, year = {2006}, pages = {1229{\textendash}1239}, publisher = {Oxford Univ Press}, author = {Bassett, S and Yousem, D and Cristinzio, C and Kusevic, I and Yassa, M and Caffo, B and Zeger, S} } @article {ndovi2006quantitative, title = {Quantitative assessment of seminal vesicle and prostate drug concentrations by use of a noninvasive method}, journal = {Clinical Pharmacology \& Therapeutics}, volume = {80}, number = {2}, year = {2006}, pages = {146{\textendash}158}, publisher = {Nature Publishing Group}, author = {Ndovi, T and Choi, L and Caffo, B and Parsons, T and Baker, S and Zhao, M and Rohde, C and Hendrix, C} } @article {Gime:Crai:Barb:Jeno:Morg:semi:2006, title = {Semiparametric Regression in Capture\textndashrecapture Modeling}, journal = {Biometrics}, volume = {62}, number = {3}, year = {2006}, pages = {691{\textendash}698}, keywords = {auxiliary variables, Bayesian inference, Demographic rates, Environmental covariates, penalized splines, Winbugs}, author = {Gimenez, O. and Crainiceanu, C and Barbraud, C. and Jenouvrier, S. and Morgan, B. J. T.} } @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. 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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} }