Stephen Correia

Brown University, Providence, Rhode Island, United States

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Publications (44)162.03 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Executive function (EF) and cognitive processing speed (CPS) are two cognitive performance domains that decline with advanced age. Reduced EF and CPS are known to correlate with age-related frontal-lobe volume loss. However, it remains unclear whether white matter microstructure in these regions is associated with age-related decline in EF and/or CPS. We utilized quantitative tractography metrics derived from diffusion-tensor MRI to investigate the relationship between the mean fiber bundle lengths (FBLs) projecting to different lobes, and EF/CPS performance in 73 healthy aging adults. We measured aspects of EF and CPS with the Trail Making Test (TMT), Color-Word Interference Test, Letter-Number Sequencing (L-N Seq), and Symbol Coding. Results revealed that parietal and occipital FBLs explained a significant portion of variance in EF. Frontal, temporal, and occipital FBLs explained a significant portion of variance in CPS. Shorter occipital FBLs were associated with poorer performance on the EF tests TMT-B and CWIT 3. Shorter frontal, parietal, and occipital FBLs were associated with poorer performance on L-N Seq and Symbol Coding. Shorter frontal and temporal FBLs were associated with lower performance on CPS tests TMT-A and CWIT 1. Shorter FBLs were also associated with increased age. Results suggest an age-related FBL shortening in specific brain regions related to poorer EF and CPS performance among older adults. Overall, results support both the frontal aging hypothesis and processing speed theory, suggesting that each mechanism is contributing to age-related cognitive decline.
    Brain Imaging and Behavior 11/2014; · 3.39 Impact Factor
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    ABSTRACT: HIV-infected individuals frequently exhibit brain dysfunction despite antiretroviral treatment. The neuropathological mechanisms underlying these abnormalities remain unclear, pointing to the importance of identifying biomarkers sensitive to brain dysfunction. We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significantly related to higher volumes of the putamen, thalamus, hippocampus, and WM. Older age was related to lower volumes in most brain regions and higher ventricular volume. Higher IFN-γ, MCP-1, and TNF-α were related to higher volumes of the putamen, pallidum, amygdala, GM, and WM. Higher IL-1β, IL-6, IL-16, IL-18, IP-10, MIP-1β, and SDF-1α were related to lower volumes of the putamen, pallidum, thalamus, hippocampus, amygdala, GM, and WM; and higher ventricular volume. The current findings provide evidence linking smaller brain volumes to HIV disease history, antiretroviral treatment, and advanced age. Cytokine markers, especially IL-6 and IL-16, showed robust association with brain volumes even after accounting for other clinical variables, demonstrating their utility in examining the mechanisms of HIV-associated brain abnormalities.
    Journal of Neuroimmune Pharmacology 10/2014; · 3.17 Impact Factor
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    ABSTRACT: To examine cognitive predictors of functional performance and dexterity using an advanced upper-limb prosthetic device.
    Archives of Clinical Neuropsychology 09/2014; 29(6):562. · 1.92 Impact Factor
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    ABSTRACT: To investigate the relationship between older age and mean cerebral white matter fiber bundle lengths (FBLs) in specific white matter tracts in the brain using quantified diffusion MRI.METHODS: Sixty-three healthy adults older than 50 years underwent diffusion tensor imaging. Tractography tracings of cerebral white matter fiber bundles were derived from the diffusion tensor imaging data.RESULTS: Results revealed significantly shorter FBLs in the anterior thalamic radiation for every 1-year increase over the age of 50 years.CONCLUSIONS: We investigated the effects of age on FBL in specific white matter tracts in the brains of healthy older individuals utilizing quantified diffusion MRI. The results revealed a significant inverse relationship between age and FBL. Longitudinal studies of FBL across a lifespan are needed to examine the specific changes to the integrity of white matter.
    Neurology 06/2014; · 8.30 Impact Factor
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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; · 9.81 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; · 8.30 Impact Factor
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    Alzheimer's and Dementia 07/2013; 9(4):P684-P685. · 17.47 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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    ABSTRACT: The Dominantly Inherited Alzheimer Network (http://dian-info.org/) study is an international clinical, biomarker and multi-modality imaging study of individuals at risk for autosomal dominant Alzheimer's disease and those already mildly affected. This prospective study of these individuals provides an opportunity to follow these individuals through different stages of the disease process, starting several years before symptoms are evident. We report here the first longitudinal analyses of cerebral and hippocampal atrophy rates from the DIAN cohort.
    Alzheimer's & dementia : the journal of the Alzheimer's Association; 07/2012
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    ABSTRACT: The Dominantly Inherited Alzheimer Network (http://dian-info.org/) study is an international clinical, biomarker and multi-modality imaging study of individuals at risk for autosomal dominant Alzheimer's disease and those already mildly affected. This prospective study of these individuals provides an opportunity to follow these individuals through different stages of the disease process, starting several years before symptoms are evident. We report here the first longitudinal analyses of cerebral and hippocampal atrophy rates from the DIAN cohort.
    Alzheimer's & Dementia; 07/2012
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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. · 9.81 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 of the United States of America. 03/2012; 109(10):3985-90.
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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: 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. · 1.92 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. · 3.61 Impact Factor

Publication Stats

413 Citations
162.03 Total Impact Points

Institutions

  • 2008–2014
    • 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
  • 2013
    • University of Missouri - St. Louis
      • Department of Psychology
      Saint Louis, Michigan, 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