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Kikinis, Zora

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Kikinis

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Zora

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Kikinis, Zora
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    Use of Anisotropy, 3D Segmented Atlas, and Computational Analysis to Identify Gray Matter Subcortical Lesions Common to Concussive Injury from Different Sites on the Cortex
    (Public Library of Science (PLoS), 2015) Kulkarni, Praveen; Kenkel, William; Finklestein, Seth; Barchet, Thomas M.; Ren, JingMei; Davenport, Mathew; Shenton, Martha; Kikinis, Zora; Nedelman, Mark; Ferris, Craig F.
    Traumatic brain injury (TBI) can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later, diffusion tensor MRI data were acquired for indices of anisotropy (IA) for use in a novel method of analysis to detect changes in gray matter microarchitecture. IA values from over 20,000 voxels were registered into a 3D segmented, annotated rat atlas covering 150 brain areas. Comparisons between left and right hemispheres revealed a small population of subcortical sites with altered IA values. Rostral and caudal concussions were of striking similarity in the impacted subcortical locations, particularly the central nucleus of the amygdala, laterodorsal thalamus, and hippocampal complex. Subsequent immunohistochemical analysis of these sites showed significant neuroinflammation. This study presents three significant findings that advance our understanding and evaluation of TBI: 1) the introduction of a new method to identify highly localized disturbances in discrete gray matter, subcortical brain nuclei without postmortem histology, 2) the use of this method to demonstrate that separate injuries to the rostral and caudal cortex produce the same subcortical, disturbances, and 3) the central nucleus of the amygdala, critical in the regulation of emotion, is vulnerable to concussion.
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    White matter microstructural abnormalities of the cingulum bundle in youths with 22q11.2 deletion syndrome: Associations with medication, neuropsychological function, and prodromal symptoms of psychosis
    (Elsevier BV, 2015) Kates, Wendy R.; Olszewski, Amy K.; Gnirke, Matthew H.; Kikinis, Zora; Nelson, Joshua; Antshel, Kevin M.; Fremont, Wanda; Radoeva, Petya D.; Middleton, Frank A.; Shenton, Martha; Coman, Ioana L.
    Background—The 22q11.2 Deletion Syndrome (22q11.2DS) is regarded as an etiologically homogenous model for understanding neuroanatomic disruptions associated with a high risk for schizophrenia. This study utilized diffusion tensor imaging (DTI) to analyze white matter microstructure in individuals with 22q11.2DS. We focused on the cingulum bundle (CB), previously shown to be disrupted in patients with schizophrenia and associated with symptoms of psychosis. Methods—White matter microstructure was assessed in the anterior, superior, and posterior CB using the tractography algorithm in DTIStudio. Neuropsychological function, presence of prodromal symptoms of psychosis, and medication history were assessed in all participants. Results—Relative to controls, young adults with 22q11.2DS showed alterations in most DTI metrics of the CB. Alterations were associated with positive prodromal symptoms of psychosis. However, when individuals with 22q11.2DS were divided by usage of antipsychotics / mood stabilizers, the medicated and non-medicated groups differed significantly in axial diffusivity of the anterior CB and in fractional anisotropy of the superior CB. DTI metrics did not differ between the medicated group and the control group. Conclusions—Results suggest that the microstructure of the CB is altered in individuals with 22q11.2DS, and that those alterations may underlie positive prodromal symptoms of psychosis. Our findings further provide preliminary evidence that antipsychotic / mood stabilizer usage may have a reparative effect on white matter microstructure in prodromal 22q11.2DS, independent of the potential effects of psychosis. Future studies of white matter pathology in individuals with 22q11.2DS should test for potential effects of medication on white matter microstructure.
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    White matter abnormalities in 22q11.2 deletion syndrome: Preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis
    (Elsevier BV, 2014-01) Perlstein, Matthew D.; Chohan, Moeed R.; Coman, Ioana L.; Antshel, Kevin M.; Fremont, Wanda P.; Gnirke, Matthew H.; Kikinis, Zora; Middleton, Frank A.; Radoeva, Petya D.; Shenton, Martha; Kates, Wendy R.; Perlstein, Matthew
    Background—This study utilized diffusion tensor imaging (DTI) to analyze white matter tractography in anterior limb of the internal capsule (ALIC), fornix, and uncinate fasciculus (UF) of individuals with 22q11.2 Deletion Syndrome and controls. Aberrations in these tracts have been previously associated with schizophrenia. With up to 25% of individuals with 22q11.2DS developing schizophrenia in adulthood, we hypothesized reduction in structural integrity of these tracts, including an association with prodromal symptoms of psychosis. We further predicted association between allelic variation in a functional polymorphism of the NoGo-66 receptor gene and 22q11.2DS white matter integrity. Methods—Tractography was conducted using fiber assignment by streamline tracking algorithm in DTI studio. Subjects were genotyped for the rs701428 SNP of the Nogo-66 receptor gene, and assessed for presence of prodromal symptoms. Results—We found significant group differences between 22q11.2DS and controls in DTI metrics for all three tracts. DTI metrics of ALIC and UF were associated with prodromal symptoms in 22q11.2DS. Further, ALIC DTI metrics were associated with allelic variation of the rs701428 SNP of the NoGo-66 receptor gene in 22q11.2DS. Conclusions—Alterations in DTI metrics suggest white matter microstructural anomalies of the ALIC, fornix, and UF in 22q11.2DS. Structural differences in ALIC appear to be associated with the Nogo-66 receptor gene, which has been linked to myelin-mediated axonal growth inhibition. Moreover, the association between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66 receptor gene may represent a susceptibility gene for psychosis through its disruption of white matter microstructure and myelin-associated axonal growth.
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    Reduced fractional anisotropy and axial diffusivity in white matter in 22q11.2 deletion syndrome: A pilot study
    (Elsevier BV, 2012) Kikinis, Zora; Asami, T.; Bouix, Sylvain; Finn, C.T.; Ballinger, T.; Tworog-Dube, E.; Kucherlapati, Raju; Kikinis, Ron; Shenton, Martha; Kubicki, Marek
    Individuals with 22q11.2 deletion syndrome (22q11.2DS) evince a 30% incidence of schizophrenia. We compared the white matter (WM) of 22q11.2DS patients without schizophrenia to a group matched healthy controls using Tract-Based-Spatial-Statistics (TBSS). We found localized reduction of Fractional Anisotropy (FA) and Axial Diffusivity (AD; measure of axonal integrity) in WM underlying the left parietal lobe. No changes in Radial Diffusivity (RD; measure of myelin integrity) were observed. Of note, studies in chronic schizophrenia patients report reduced FA, no changes in AD, and increases in RD in WM. Our findings suggest different WM microstructure in 22q11.2DS than in patients with schizophrenia.
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    White matter tract abnormalities between rostral middle frontal gyrus, inferior frontal gyrus and striatum in first-episode schizophrenia
    (Elsevier BV, 2013) Quan, Meina; Lee, Sang-Hyuk; Kubicki, Marek; Kikinis, Zora; Rathi, Yogesh; Seidman, Larry Joel; Mesholam-Gately, Raquelle; Goldstein, Jill; McCarley, Robert William; Shenton, Martha; Levitt, James
    Background—Previous studies have shown that frontostriatal networks, especially those involving dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) mediate cognitive functions some of which are abnormal in schizophrenia. This study examines white matter integrity of the tracts connecting DLPFC/VLPFC and striatum in patients with firstepisode schizophrenia (FESZ), and their associations with cognitive and clinical correlates. Methods—Diffusion tensor and structural magnetic resonance images were acquired on a 3T GE Echospeed system from 16 FESZ and 18 demographically comparable healthy controls. FreeSurfer software was used to parcellate regions of interest. Two-tensor tractography was applied to extract fibers connecting striatum with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. DTI indices, including fractional anisotropy (FA), trace, axial diffusivity (AD) and radial diffusivity (RD), were used for group comparisons. Additionally, correlations were evaluated between these diffusion indices and the Wisconsin Card Sorting Task (WCST) and the Brief Psychiatric Rating Scale (BPRS). Results—FA was significantly reduced in the left IFG-striatum tract, whereas trace and RD were significantly increased in rMFG-striatum and IFG-striatum tracts, bilaterally. The number of WCST categories completed correlated positively with FA of the right rMFG-striatum tract, and negatively with trace and RD of right rMFG-striatum and right IFG-striatum tracts in FESZ. The BPRS scores did not correlate with these indices. Conclusions—These data suggest that white matter tract abnormalities between rMFG/IFG and striatum are present in FESZ and appear to be significantly associated with executive dysfunction but not with symptom severity.
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    Gray matter volume reduction in rostral middle frontal gyrus in patients with chronic schizophrenia
    (Elsevier BV, 2010) Kikinis, Zora; Fallon, J.H.; Niznikiewicz, Margaret; Nestor, Paul; Davidson, C.; Bobrow, L.; Pelavin, P.E.; Fischl, Bruce; Yendiki, Anastasia; McCarley, Robert William; Kikinis, Ron; Kubicki, Marek; Shenton, Martha
    The dorsolateral prefrontal cortex (DLPFC) is a brain region that has figured prominently in studies of schizophrenia and working memory, yet the exact neuroanatomical localization of this brain region remains to be defined. DLPFC primarily involves the superior frontal gyrus and middle frontal gyrus (MFG). The latter, however is not a single neuroanatomical entity but instead is comprised of rostral (anterior, middle, and posterior) and caudal regions. In this study we used structural MRI to develop a method for parcellating MFG into its component parts. We focused on this region of DLPFC because it includes BA46, a region involved in working memory. We evaluated volume differences in MFG in 20 patients with chronic schizophrenia and 20 healthy controls. Mid-rostral MFG (MR-MFG) was delineated within the rostral MFG using anterior and posterior neuroanatomical landmarks derived from cytoarchitectonic definitions of BA46. Gray matter volumes of MR-MFG were then compared between groups, and a significant reduction in gray matter volume was observed (p < 0.008), but not in other areas of MFG (i.e., anterior or posterior rostral MFG, or caudal regions of MFG). Our results demonstrate that volumetric alterations in MFG gray matter are localized exclusively to MR-MFG. 3D reconstructions of the cortical surface made it possible to follow MFG into its anterior part, where other approaches have failed. This method of parcellation offers a more precise way of measuring MR-MFG that will likely be important in further documentation of DLPFC anomalies in schizophrenia.
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    The social brain network in 22q11.2 deletion syndrome: a diffusion tensor imaging study
    (BioMed Central, 2017) Olszewski, Amy K.; Kikinis, Zora; Gonzalez, Christie S.; Coman, Ioana L.; Makris, Nikolaos; Gong, Xue; Rathi, Yogesh; Zhu, Anni; Antshel, Kevin M.; Fremont, Wanda; Kubicki, Marek; Bouix, Sylvain; Shenton, Martha; Kates, Wendy R.
    Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls. Results: Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis. Conclusions: Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS. Electronic supplementary material The online version of this article (doi:10.1186/s12993-017-0122-7) contains supplementary material, which is available to authorized users.
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    Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome
    (Springer Science + Business Media, 2013) Kikinis, Zora; Makris, Nikos; Finn, Christine; Bouix, Sylvain; Lucia, Diandra; Coleman, Michael; Tworog-Dube, Erica; Kikinis, Ron; Kucherlapati, Raju; Shenton, Martha; Kubicki, Marek
    Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA) (measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.
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    Diffusion imaging of mild traumatic brain injury in the impact accelerated rodent model: A pilot study
    (Informa UK Limited, 2017-06-19) Kikinis, Zora; Pasternak, Ofer; Peled, Sharon; Bouix, Sylvain; Rathi, Yogesh; Muehlmann, Marc; Kulkarni, Praveen; Ferris, Craig; Koerte, Inga; Pieper, Steve; Yarmarkovich, Alexander; Porter, Caryn; Kristal, Bruce; Shenton, Martha
    PRIMARY OBJECTIVE: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. RESEARCH DESIGN: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls. Seven days post injury, DTI was acquired from fixed rat brains using a 7T scanner. Group comparison of Fractional Anisotropy (FA) values between traumatized and sham animals was performed using Tract-Based Spatial Statistics (TBSS), a method that we adapted for rats. MAIN OUTCOMES AND RESULTS: TBSS revealed white matter regions of the brain with increased FA values in the traumatized versus sham rats, localized mainly to the contrecoup region. Regions of increased FA included the pyramidal tract, the cerebral peduncle, the superior cerebellar peduncle and to a lesser extent the fibre tracts of the corpus callosum, the anterior commissure, the fimbria of the hippocampus, the fornix, the medial forebrain bundle and the optic chiasm. CONCLUSION: Seven days post injury, during the period of tissue reparation in the impact acceleration rat model of mTBI, microstructural changes to white matter can be detected using DTI.