@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 {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 {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 {828, title = {Axial 3D gradient-echo imaging for improved multiple sclerosis lesion detection in the cervical spinal cord at 3T.}, journal = {Neuroradiology}, volume = {55}, year = {2013}, month = {2013 Mar}, pages = {431-9}, abstract = {

INTRODUCTION: In multiple sclerosis (MS), spinal cord imaging can help in diagnosis and follow-up evaluation. However, spinal cord magnetic resonance imaging (MRI) is technically challenging, and image quality, particularly in the axial plane, is typically poor compared to brain MRI. Because gradient-recalled echo (GRE) images might offer improved contrast resolution within the spinal cord at high magnetic field strength, both without and with a magnetization transfer prepulse, we compared them to T2-weighted fast-spin-echo (T2-FSE) images for the detection of MS lesions in the cervical cord at 3T.

METHODS: On a clinical 3T MRI scanner, we studied 62 MS cases and 19 healthy volunteers. Axial 3D GRE sequences were performed without and with off-resonance radiofrequency irradiation. To mimic clinical practice, all images were evaluated in conjunction with linked images from a sagittal short tau inversion recovery scan, which is considered the gold standard for lesion detection in MS. Two experienced observers recorded image quality, location and size of focal lesions, atrophy, swelling, and diffuse signal abnormality independently at first and then in consensus.

RESULTS: The number and volume of lesions detected with high confidence was more than three times as high on both GRE sequences compared to T2-FSE (p < 0.0001). Approximately 5 \% of GRE scans were affected by artifacts that interfered with image interpretation, not significantly different from T2W-FSE.

CONCLUSIONS: Axial 3D GRE sequences are useful for MS lesion detection when compared to 2D T2-FSE sequences in the cervical spinal cord at 3T and should be considered when examining intramedullary spinal cord lesions.

}, keywords = {Adult, Aged, Algorithms, Cervical Vertebrae, Echo-Planar Imaging, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Imaging, Three-Dimensional, Male, Middle Aged, Multiple Sclerosis, Reproducibility of Results, Sensitivity and Specificity, Spinal Cord}, issn = {1432-1920}, doi = {10.1007/s00234-012-1118-5}, author = {Ozturk, Arzu and Aygun, Nafi and Smith, Seth A and Caffo, Brian and Calabresi, Peter A and Reich, Daniel S} } @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 {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 {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 {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 {708, title = {Arsenic exposure, diabetes prevalence, and diabetes control in the Strong Heart Study.}, journal = {Am J Epidemiol}, volume = {176}, year = {2012}, month = {2012 Nov 15}, pages = {865-74}, abstract = {

This study evaluated the association of arsenic exposure, as measured in urine, with diabetes prevalence, glycated hemoglobin, and insulin resistance in American Indian adults from Arizona, Oklahoma, and North and South Dakota (1989-1991). We studied 3,925 men and women 45-74 years of age with available urine arsenic measures. Diabetes was defined as a fasting glucose level of 126 mg/dL or higher, a 2-hour glucose level of 200 mg/dL or higher, a hemoglobin A1c (HbA1c) of 6.5\% or higher, or diabetes treatment. Median urine arsenic concentration was 14.1 {\textmu}g/L (interquartile range, 7.9-24.2). Diabetes prevalence was 49.4\%. After adjustment for sociodemographic factors, diabetes risk factors, and urine creatinine, the prevalence ratio of diabetes comparing the 75th versus 25th percentiles of total arsenic concentrations was 1.14 (95\% confidence interval: 1.08, 1.21). The association between arsenic and diabetes was restricted to participants with poor diabetes control (HbA1c >=8\%). Arsenic was positively associated with HbA1c levels in participants with diabetes. Arsenic was not associated with HbA1c or with insulin resistance (assessed by homeostatic model assessment to quantify insulin resistance) in participants without diabetes. Urine arsenic was associated with diabetes control in a population from rural communities in the United States with a high burden of diabetes. Prospective studies that evaluate the direction of the relation between poor diabetes control and arsenic exposure are needed.

}, keywords = {Aged, Arizona, Arsenicals, Blood Glucose, Creatinine, Diabetes Mellitus, Environmental Exposure, Female, Hemoglobin A, Glycosylated, Humans, Indians, North American, Male, Middle Aged, North Dakota, Oklahoma, Poisson Distribution, Prevalence, Regression Analysis, Risk Factors, South Dakota}, issn = {1476-6256}, doi = {10.1093/aje/kws153}, author = {Gribble, Matthew O and Howard, Barbara V and Umans, Jason G and Shara, Nawar M and Francesconi, Kevin A and Goessler, Walter and Crainiceanu, Ciprian M and Silbergeld, Ellen K and Guallar, Eliseo and Navas-Acien, Ana} } @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 {622, title = {Dynamics of large-scale cortical interactions at high gamma frequencies during word production: event related causality (ERC) analysis of human electrocorticography (ECoG).}, journal = {Neuroimage}, volume = {56}, year = {2011}, month = {2011 Jun 15}, pages = {2218-37}, abstract = {

Intracranial EEG studies in humans have shown that functional brain activation in a variety of functional-anatomic domains of human cortex is associated with an increase in power at a broad range of high gamma (\>60Hz) frequencies. Although these electrophysiological responses are highly specific for the location and timing of cortical processing and in animal recordings are highly correlated with increased population firing rates, there has been little direct empirical evidence for causal interactions between different recording sites at high gamma frequencies. Such causal interactions are hypothesized to occur during cognitive tasks that activate multiple brain regions. To determine whether such causal interactions occur at high gamma frequencies and to investigate their functional significance, we used event-related causality (ERC) analysis to estimate the dynamics, directionality, and magnitude of event-related causal interactions using subdural electrocorticography (ECoG) recorded during two word production tasks: picture naming and auditory word repetition. A clinical subject who had normal hearing but was skilled in American Signed Language (ASL) provided a unique opportunity to test our hypothesis with reference to a predictable pattern of causal interactions, i.e. that language cortex interacts with different areas of sensorimotor cortex during spoken vs. signed responses. Our ERC analyses confirmed this prediction. During word production with spoken responses, perisylvian language sites had prominent causal interactions with mouth/tongue areas of motor cortex, and when responses were gestured in sign language, the most prominent interactions involved hand and arm areas of motor cortex. Furthermore, we found that the sites from which the most numerous and prominent causal interactions originated, i.e. sites with a pattern of ERC "divergence", were also sites where high gamma power increases were most prominent and where electrocortical stimulation mapping interfered with word production. These findings suggest that the number, strength and directionality of event-related causal interactions may help identify network nodes that are not only activated by a task but are critical to its performance.

}, keywords = {brain mapping, Cerebral Cortex, Electroencephalography, Female, Humans, Middle Aged, Neural Pathways, Seizures, Signal Processing, Computer-Assisted, Speech}, issn = {1095-9572}, doi = {10.1016/j.neuroimage.2011.03.030}, author = {Korzeniewska, A. and Franaszczuk, Piotr J. and Crainiceanu, C and Ku{\'s}, Rafa{\l} and Crone, Nathan E.} }