Stephen Correia

Brown University, Providence, Rhode Island, United States

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Publications (39)101.17 Total impact

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    ABSTRACT: Major imaging biomarkers of Alzheimer's disease include amyloid deposition [imaged with [(11)C]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [(18)F]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now extend this work to include a larger cohort, whole-brain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimer's disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease.
    Proceedings of the National Academy of Sciences 11/2013; · 9.74 Impact Factor
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    ABSTRACT: Chronic systemic immune activation and inflammatory processes have been linked to brain dysfunction in medically stable HIV-infected people. We investigated the association between verbal memory performance and plasma concentrations of 13 cytokines measured using multiplexed bead array immunoassay in 74 HIV-seropositive individuals and 50 HIV-seronegative controls. Memory performance was positively related to levels of IL-8 and IFN-γ, and negatively related to IL-10 and IL-18 and to hepatitis C infection. Memory performance was not significantly related to HIV disease markers. The results indicate the importance of systemic immune and inflammatory markers to neurocognitive function in chronic and stable HIV disease.
    Journal of neuroimmunology 09/2013; · 2.84 Impact Factor
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    ABSTRACT: To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network. Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO). We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO. Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease.
    Neurology 07/2013; · 8.25 Impact Factor
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    ABSTRACT: The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer's disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N = 23) versus no e4 allele (non-carriers, N = 41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p = .038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.
    Brain Imaging and Behavior 03/2013; · 2.67 Impact Factor
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    ABSTRACT: Objective: Presentation of an unusual case of amnesic syndrome following a suspected AVM. The subject was a 14-year-old female (N) who suffered a large right temporo-parietal intra-parenchymal hemorrhage with extension into the ventricular system requiring surgical evacuation. She presented with a significant anterograde amnesic disorder that was generalized and not circumscribed to the visual domain. A neuropsychological assessment was recommended to investigate the nature and extent of her amnesic symptoms. Two aspects were found to be fundamental in this case, firstly, the inconsistency between the image findings of acute cerebral injury and her general amnesic disorder, and secondly, her capacity to keep up with academic demands despite persisting memory impairment. Method: N was assessed on four occasions over a period of 4 years to monitor her recovery. The initial assessment was comprehensive and covered intellectual functions, attention, processing speed, general memory, and executive functions. The subsequent reviews targeted for the most part the areas of impairment to evaluate the recovery process. Follow-up MRI findings were also reviewed. Results: The initial neuropsychological findings 5-6 weeks post-injury confirmed the presence of a moderate to severe impairment in general memory. Subsequent reviews indicated some gains overall, but she demonstrated persisting mild memory dysfunctions particularly in the area of visual memory. Conclusions: Ns general memory impairment was surprising given her right hemispheric injury. Her profile suggested some probable left hemispheric injury. Ns grades at school indicated that her mild memory impairments were not affecting her ability to keep up academically at a level that was consistent with her intellectual ability. The etiology of her memory impairment as well as the course of recovery over time will discussed.
    Archives of Clinical Neuropsychology 09/2012; 27(6):576-685. · 2.00 Impact Factor
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    Alzheimer's and Dementia 07/2012; 8(4):P72-P73. · 14.48 Impact Factor
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    ABSTRACT: Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.
    Proceedings of the National Academy of Sciences 03/2012; 109(10):3985-90. · 9.74 Impact Factor
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    ABSTRACT: HIV-infected people frequently exhibit brain dysfunction characterized by preferential damage to the cerebral white matter. Despite suppressed viral load and reconstituted immune function afforded by combination antiretroviral therapy (CART), brain dysfunction continues to be observed even in medically stable individuals. To provide insight into the etiology of HIV-associated brain dysfunction in the CART era, we examined the effects of HIV disease markers, antiretroviral treatment, hepatitis C (HCV) coinfection, and age on DTI measures of white matter integrity in a cohort of 85 individuals aged 23 to 65 years with chronic HIV infection. Fractional anisotropy and mean diffusivity were derived from 29 cerebral white matter regions, which were segmented on each individual brain using a high-resolution T1-weighted image and registered to diffusion images. Significant effects of clinical variables were found on white matter abnormalities in nearly all brain regions examined. Most notably, HCV coinfection and older age were associated with decreased anisotropy or increased diffusivity in the majority of brain regions. Individuals with higher current CD4 levels exhibited higher anisotropy in parietal lobe regions, while those undergoing antiretroviral treatment exhibited higher anisotropy in temporal lobe regions. The observed diffuse pattern of white matter injury suggests that future neuroimaging studies should employ methodologies that are not limited to circumscribed regions of interest. The current findings underline the multifactorial nature of HIV-associated brain dysfunction in the CART era, and the importance of examining the effects of HIV disease in the context of other comorbidities, in particular HCV coinfection and aging.
    Journal of NeuroVirology 10/2011; 17(5):477-86. · 2.85 Impact Factor
  • Stephen Correia, Assawin Gongvatana
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    ABSTRACT: Historically, the role of white matter in human cognition and behavior has received less attention than that of gray matter (Filley, The Behavioral Neurology of White Matter, 2001). It was not until the 1960s that Geschwind (1926–1984) firmly established the importance of white matter in supporting normal mental activity in his classic work on disconnection syndromes (Geschwind, Brain 88:237–294, 585–644, 1965; Geschwind and Kaplan, Neurology 12:675–685, 1962). Since then, interest in the role of white matter in cognition, emotion, and behavior has grown. By the late 1980s, magnetic resonance imaging (MRI) was widely adopted for detecting brain disorders. The introduction of diffusion-tensor imaging (DTI) in the mid-1990s (Basser, NMR Biomed 8:333–344, 1995; Basser et al., J Magn Reson B 103:247–254, 1994; Basser et al., Biophys J 66:259–267, 1994) provided a new in vivo MRI tool for gaining unprecedented insight into the structure of white matter and its functional correlates. DTI provides information about the structural coherence and topography of biological tissue based on the measurement of rate and direction of water diffusion. DTI is particularly useful in fibrous tissue such as cerebral white matter or muscle where the linear arrangement of cell structures constrains water to diffuse faster along the fibers than in other directions.
    09/2010: pages 49-66;
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    ABSTRACT: The evaluation of bilingual children is a complicated endeavor because there are various views of how bilingualism affects brain organization and functioning. Added to that is the challenge of determining language development of Hispanic children living in a monolingual Spanish-speaking home in a Spanish-speaking country, but mostly exposed to English language television programming and, in some cases, English language school curriculum. Our case will review the evaluation process of a 14-year-old Puerto Rican boy with previous diagnoses of expressive language disorder and Attention-deficit/Hyperactivity Disorder (ADHD). The neuropsychological evaluation revealed an IQ within the average range, with significant differences between the perceptual reasoning, verbal comprehension, and processing speed. The case will summarize performance in verbal, executive, and psycho-educational measures with a thorough review of his developmental history and the interpretation of these neuropsychological achievement and behavioral measures in light of other variables influencing his difficulties.
    Archives of Clinical Neuropsychology 09/2010; 25(6):475-583. · 2.00 Impact Factor
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    ABSTRACT: Dysfunction in circuits linking frontal cortex and basal ganglia (BG) is strongly implicated in obsessive-compulsive disorder (OCD). On MRI studies, neuropsychiatric disorders with known BG pathology have abnormally short T2 relaxation values (a putative biomarker of elevated iron) in this region. We asked if BG T2 values are abnormal in OCD. We measured volume and T2 and T1 relaxation rates in BG of 32 adults with OCD and 33 matched controls. There were no group differences in volume or T1 values in caudate, putamen, or globus pallidus (GP). The OCD group had lower T2 values (suggesting higher iron content) in the right GP, with a trend in the same direction for the left GP. This effect was driven by patients whose OCD symptoms began from around adolescence to early adulthood. The results suggest a possible relationship between age of OCD onset and iron deposition in the basal ganglia.
    Brain Imaging and Behavior 03/2010; 4(1):35-45. · 2.67 Impact Factor
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    ABSTRACT: CADASIL is a genetic vascular dementia caused by mutations in the Notch 3 gene on Chromosome 19. However, little is known about the mechanisms of vascular degeneration. We characterized upstream components of Notch signaling pathways that may be disrupted in CADASIL, by measuring expression of insulin, IGF-1, and IGF-2 receptors, Notch 1, Notch 3, and aspartyl-(asparaginyl)-β-hydroxylase (AAH) in cortex and white matter from 3 CADASIL and 6 control brains. We assessed CADASIL-associated cell loss by measuring mRNA corresponding to neurons, oligodendroglia, and astrocytes, and indices of vascular degeneration by measuring smooth muscle actin (SMA) and endothelin-1 expression in isolated vessels. Immunohistochemical staining was used to assess SMA degeneration. Significant abnormalities, including reduced cerebral white matter mRNA levels of Notch 1, Notch 3, AAH, SMA, IGF receptors, myelin-associated glycoproteins, and glial fibrillary acidic protein, and reduced vascular expression of SMA, IGF receptors, Notch 1, and Notch 3 were detected in CADASIL-lesioned brains. In addition, we found CADASIL-associated reductions in SMA, and increases in ubiquitin immunoreactivity in the media of white matter and meningeal vessels. No abnormalities in gene expression or immunoreactivity were observed in CADASIL cerebral cortex. In conclusion, molecular abnormalities in CADASIL are largely restricted to white matter and white matter vessels, corresponding to the distribution of neuropathological lesions. These preliminary findings suggest that CADASIL is mediated by both glial and vascular degeneration with reduced expression of IGF receptors and AAH, which regulate Notch expression and function.
    Journal of Alzheimer's disease: JAD 01/2010; 21(4):1393-402. · 4.17 Impact Factor
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    ABSTRACT: Visual exploration is essential to the visualization and analysis of densely sampled 3D DTI fibers in biological specimens, due to the high geometric, spatial, and anatomical complexity of fiber tracts. Previous methods for DTI fiber visualization use zooming, color-mapping, selection, and abstraction to deliver the characteristics of the fibers. However, these schemes mainly focus on the optimization of visualization in the 3D space where cluttering and occlusion make grasping even a few thousand fibers difficult. This paper introduces a novel interaction method that augments the 3D visualization with a 2D representation containing a low-dimensional embedding of the DTI fibers. This embedding preserves the relationship between the fibers and removes the visual clutter that is inherent in 3D renderings of the fibers. This new interface allows the user to manipulate the DTI fibers as both 3D curves and 2D embedded points and easily compare or validate his or her results in both domains. The implementation of the framework is GPU based to achieve real-time interaction. The framework was applied to several tasks, and the results show that our method reduces the user's workload in recognizing 3D DTI fibers and permits quick and accurate DTI fiber selection.
    IEEE Transactions on Visualization and Computer Graphics 01/2010; 15(6):1433-40. · 1.90 Impact Factor
  • Stephen Salloway, Stephen Correia
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    ABSTRACT: Basic research is bringing a much-needed infusion of optimism and urgency to the clinical diagnosis and treatment of Alzheimer disease. Some of its risk factors may be modifiable, and although current drugs offer only modest benefit, true disease-modifying drugs are on the horizon. This review is aimed at primary care physicians, who are the first clinicians to see patients with Alzheimer disease and are responsible for their ongoing care throughout the course of their dementia.
    Cleveland Clinic Journal of Medicine 02/2009; 76(1):49-58. · 3.40 Impact Factor
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    Wei Chen, Song Zhang, Stephen Correia, David F. Tate
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    ABSTRACT: Diffusion tensor fields reveal the underlying anatomical structures in biological tissues such as neural fibers in the brain. Most current methods for visualizing the diffusion tensor field can be categorized into two classes: integral curves and glyphs. Integral curves are continuous and represent the underlying fiber structures, but are prone to integration error and loss of local information. Glyphs are useful for representing local tensor information, but do not convey the connectivity in the anatomical structures well. We introduce a simple yet effective visualization technique that extends the streamball method in flow visualization to tensor ellipsoids. Each tensor ellipsoid represents a local tensor, and either blends with neighboring tensors or breaks away from them depending on their orientations and anisotropies. The resulting visualization shows the connectivity information in the underlying anatomy while characterizing the local tenors in detail. By interactively changing an iso-value parameter, users can examine the diffusion tensor field in the entire spectrum between the continuous integral curves and the discrete glyphs. Expert evaluation indicates that this method conveys very useful visual information about local anisotropy in white matter fibers. Such information was previously unavailable in tractography models. Our method provides a visual tool for assessing variability in DTI fiber tract integrity and its relation to function.
    IEEE Pacific Visualization Symposium PacificVis 2009, Beijing, China, April 20-23, 2009; 01/2009
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    NeuroImage 01/2009; 46(1):344-344. · 6.25 Impact Factor
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    Song Zhang, Stephen Correia, David H Laidlaw
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    ABSTRACT: We present a method for clustering diffusion tensor imaging (DTI) integral curves into anatomically plausible bundles. An expert rater evaluated the anatomical accuracy of the bundles. We also evaluated the method by applying an experimental cross-subject labeling method to the clustering results. We first employ a sampling and culling strategy for generating DTI integral curves and then constrain the curves so that they terminate in gray matter. We then employ a clustering method based on a proximity measure calculated between every pair of curves. We interactively selected a proximity threshold to achieve visually optimal clustering in models from four DTI datasets. An expert rater then assigned a confidence rating about bundle presence and accuracy for each of 12 target fiber bundles of varying calibers and type in each dataset. We then created a fiber bundle template to cluster and label the fiber bundles automatically in new datasets. According to expert evaluation, the automated proximity-based clustering and labeling algorithm consistently yields anatomically plausible fiber bundles on large and coherent clusters. This work has the potential to provide an automatic and robust way to find and study neural fiber bundles within DTI.
    IEEE Transactions on Visualization and Computer Graphics 10/2008; 14(5):1044-53. · 1.90 Impact Factor
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    ABSTRACT: We present new quantitative diffusion-tensor imaging (DTI) tractography-based metrics for assessing cerebral white matter integrity. These metrics extend prior work in this area. Tractography models of cerebral white matter were produced from each subject's DTI data. The models are a set of curves (e.g., "streamtubes") derived from DTI data that represent the underlying topography of the cerebral white matter. Nine metrics were calculated in whole brain tractography models and in three "tracts-of-interest": transcallosal fibers and the left and right cingulum bundles. The metrics included the number of streamtubes and several other based on the summed length of streamtubes, including some that were weighted by scalar anisotropy metrics and normalized for estimated intracranial volume. We then tested whether patients with subcortical ischemic vascular disease (i.e., vascular cognitive impairment or VCI) vs. healthy controls (HC) differed on the metrics. The metrics were significantly lower in the VCI group in whole brain and in transcallosal fibers but not in the left or right cingulum bundles. The metrics correlated significantly with cognitive functions known to be impacted by white matter abnormalities (e.g., processing speed) but not with those more strongly impacted by cortical disease (e.g., naming). These new metrics help bridge the gap between DTI tractography and scalar analytical methods and provide a potential means for examining group differences in white matter integrity in specific tracts-of-interest.
    NeuroImage 06/2008; 42(2):568-81. · 6.25 Impact Factor
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    ABSTRACT: This paper reviews the key lessons learned from the first published short-term, placebo-controlled trial of a cholinesterase inhibitor for treatment of mild cognitive impairment (MCI). The study was a 24-week placebo-controlled trial designed to evaluate the efficacy and safety of donepezil HCl (donepezil) in the treatment of cognitive impairment in subjects with MCI. Primary outcome measures were the NYU Paragraphs Test and the ADCS Clinicians Global-Impression of Change in the intent-to-treat last-observation-carried-forward group. There was no benefit of donepezil treatment on primary outcome measures (NYU Paragraphs and ADCS CGI-C) in the ITT-LOCF group but positive findings were seen on NYU Paragraphs in the fully evaluable group and in certain secondary outcome measures across both groups. The results highlight the need for the use of primary cognitive and functional measures that are reliable and sensitive to change in patients with MCI. Measures of episodic memory, psychomotor speed and complex attention were most sensitive in this study. Functional rating scales are needed that measure change in individual subjects' key areas of functional deficit, which typically involve executive aspects of instrumental ADLs. Tolerability can be increased by use of flexible dosing and efficacy is likely to be enhanced by increasing the length of the trial from six to 12 months and by enriching the sample with subjects more likely to decline during the trial.
    International Psychogeriatrics 03/2008; 20(1):40-6. · 2.19 Impact Factor
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    Wenjin Zhou, Stephen Correia, David H Laidlaw
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    ABSTRACT: We present a set of findings from our user evaluation of state-of-the-art TOI selection techniques. Tractography is a standard approach for visualizing the brain's white matter structure that is based on dif-fusion tensor imaging (DTI), and brain scientists need very efficient tools to select tracts-of-interest (TOI) for their research. We per-formed two evaluations aimed at better understanding of the tools: a subjective study of three standard TOI selection tools looking at the utility, usability and user satisfaction with the design features, and a user performance evaluation to measure the time performance and subjective reliability of two of the three standard TOI selection tools. Index Terms: J.3 [LIFE AND MEDICAL SCIENCES]: Medical information systems— 1 INTRODUCTION The most popular approach to extract the underlying fiber struc-ture from DTI data is tractography: reconstructing trajectories from DTI using streamtubes/streamlines. Selecting TOI for segmenta-tion is the most frequent task in most clinical research studies using DTI tractography, such as [5]. Several TOI selection techniques have been proposed to allow expert users to obtain clustering in-teractively [3, 2, 4, 7]. Different TOI selection methods give users different levels of flexibility and efficiency in clustering the fiber tracts. It is unclear which TOI selection method and combination of interaction techniques gives the expert user the best tools for the clustering task, and to the best of our knowledge, no studies have compared TOI selection techniques. We present the results from our user study evaluating the design features in three different TOI selection tools. We hope that this study will improve the design of TOI selection tools and thus help brain scientists in brain diagnoses.
    IEEE Visualization Poster Com- pendium. 02/2008;

Publication Stats

279 Citations
304 Downloads
3k Views
101.17 Total Impact Points

Institutions

  • 2008–2013
    • Brown University
      • • Department of Psychiatry and Human Behavior
      • • Department of Computer Science
      Providence, Rhode Island, United States
    • Mississippi State University
      • Department of Computer Science and Engineering
      Starkville, MS, United States
  • 2007–2009
    • Alpert Medical School - Brown University
      • Department of Psychiatry and Human Behavior
      Providence, Rhode Island, United States
  • 2006–2009
    • Butler Hospital
      Providence, Rhode Island, United States