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Levitt, James

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Levitt

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James

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Levitt, James
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    Attentional Control and Intelligence: MRI Orbital Frontal Gray Matter and Neuropsychological Correlates
    (Hindawi Publishing Corporation, 2015) Nestor, Paul; Nakamura, Motoaki; Niznikiewicz, Margaret; Levitt, James; Newell, Dominick T.; Shenton, Martha; McCarley, Robert William
    Attentional control is a key function of working memory that is hypothesized to play an important role in psychometric intelligence. To test the neuropsychological underpinnings of this hypothesis, we examined full-scale IQ, as measured by the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), and attentional control, as measured by Trails B response time and Wisconsin Card Sorting (WCS) test perseverative errors in 78 healthy participants, 25 of whom also had available magnetic resonance imaging (MRI) gray matter volume studies of the orbital frontal cortex (OFC) parcellated into three regions: gyrus rectus, middle orbital gyrus, and lateral orbital gyrus. Hierarchical regression indicated that Trails B response time specifically explained 15.13% to 19.18% of the variation in IQ and WCS perseverative errors accounted for an additional 8.12% to 11.29% of the variance. Full-scale IQ correlated very strongly with right middle orbital gyrus gray matter volume (r = 0.610, p = 0.002), as did Trails B response time with left middle orbital gyrus gray matter volume (r = −0.608, p = 0.003). Trails B response time and right middle orbital gyrus gray matter volume jointly accounted for approximately 32.95% to 54.82% of the variance in IQ scores. These results provided evidence of the unique contributions of attentional control and OFC gray matter to intelligence.
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    Orbitofrontal volume deficit in schizophrenia and thought disorder
    (Oxford University Press (OUP), 2008) Nakamura, M.; Nestor, Paul; Levitt, James; Cohen, Adam; Kawashima, T.; Shenton, Martha; McCarley, Robert William
    Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card SortingTest, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F1,47=17.4, P= 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F1,47=19.2, P<0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (χ2=12.49, P= 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse `positive formal thought disorder' (r=−0.638, P= 0.001), and a smaller right MiOG with a longer duration of the illness (r=−0.618, P= 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r=0.541, P= 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r=−0.608, P= 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.
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    MRI Study of Caudate Nucleus Volume and Its Cognitive Correlates in Neuroleptic-Naive Patients With Schizotypal Personality Disorder
    (American Psychiatric Publishing, 2002) Levitt, James; McCarley, Robert William; Dickey, Chandlee; Voglmaier, Martina; Niznikiewicz, Margaret; Seidman, Larry Joel; Hirayasu, Yoshio; Ciszewski, Aleksandra A.; Kikinis, Ron; Jolesz, Ferenc; Shenton, Martha
    Objective: “Cognitive” circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. Method: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. Results: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. Conclusions: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.
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    Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study
    (Elsevier BV, 2001) Wible, Cynthia Gayle; Anderson, Jane; Shenton, Martha; Kricun, Ashley; Hirayasu, Yoshio; Tanaka, Shin; Levitt, James; O, Brian F; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert William
    The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial–temporal lobe regions — two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal–prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.
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    Abnormal Angular Gyrus Asymmetry in Schizophrenia
    (American Psychiatric Publishing, 2000) Niznikiewicz, Margaret; Donnino, Robert; McCarley, Robert William; Nestor, Paul; Iosifescu, Daniel V.; O'Donnell, Brian; Levitt, James; Shenton, Martha
    Objective: Few studies have evaluated the parietal lobe in schizophrenia despite the fact that it has an important role in attention, memory, and language—all functions that have been reported to be abnormal in schizophrenia. The inferior parietal lobule, in particular, is of interest because it is not only part of the heteromodal association cortex but also is part of the semantic-lexical network, which also includes the planum temporale. Both the inferior parietal lobule, particularly the angular gyrus of the inferior parietal lobule, and the planum temporale are brain regions that play a critical role as biological substrates of language and thought. The authors compared volume and asymmetry measures of the individual gyri of the parietal lobe by means of magnetic resonance imaging (MRI) scans. Method: MRI scans with a 1.5-Tesla magnet were obtained from 15 male chronic schizophrenic and 15 comparison subjects matched for age, gender, and parental socioeconomic status. Results: Inferior parietal lobule volumes showed a leftward asymmetry (left 7.0% larger than right) in comparison subjects and a reversed asymmetry (left 6.3% smaller than right) in schizophrenic subjects. The angular gyrus accounted for this difference in asymmetry, with the left angular gyrus being significantly larger (18.7%) than the right in comparison subjects, a finding that was not observed in schizophrenic patients. A further test of angular gyrus asymmetry showed a reversal of the normal left-greater-than-right asymmetry in the schizophrenic patients. Conclusions: Patients with schizophrenia showed a reversed asymmetry in the inferior parietal lobule that was localized to the angular gyrus, a structure belonging to the heteromodal association cortex as well as being part of the semantic-lexical network. This finding contributes to a more comprehensive understanding of the neural substrates of language and thought disorder in schizophrenia.
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    MRI anatomy of schizophrenia
    (Elsevier BV, 1999) McCarley, Robert William; Wible, Cynthia Gayle; Frumin, Melissa; Hirayasu, Yoshio; Levitt, James; Fischer, Iris A.; Shenton, Martha
    Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer–reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a “two– hit” model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia.
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    A Unifying Approach to Registration, Segmentation, and Intensity Correction
    (Springer Science + Business Media, 2005) Pohl, Kilian M.; Fisher, John; Levitt, James; Shenton, Martha; Kikinis, Ron; Grimson, William Eric Leifur; Wells, William
    We present a statistical framework that combines the registration of an atlas with the segmentation of magnetic resonance images. We use an Expectation Maximization-based algorithm to find a solution within the model, which simultaneously estimates image inhomogeneities, anatomical labelmap, and a mapping from the atlas to the image space. An example of the approach is given for a brain structure-dependent affine mapping approach. The algorithm produces high quality segmentations for brain tissues as well as their substructures. We demonstrate the approach on a set of 22 magnetic resonance images. In addition, we show that the approach performs better than similar methods which separate the registration and segmentation problems.
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    Smaller Neocortical Gray Matter and Larger Sulcal Cerebrospinal Fluid Volumes in Neuroleptic-Naive Women With Schizotypal Personality Disorder
    (American Medical Association (AMA), 2006) Koo, Min-Seong; Dickey, Chandlee; Park, Hae-Jeong; Kubicki, Marek; Ji, Na Young; Bouix, Sylvain; Pohl, Kilian M.; Levitt, James; Nakamura, Motoaki; Shenton, Martha; McCarley, Robert William
    Context: Structural brain abnormalities, including larger cerebrospinal fluid (CSF) volumes, have been observed in men diagnosed as having schizotypal personality disorder (SPD). Objectives: To determine whether women with SPD have abnormalities similar to those of men with SPD and to elucidate specific SPD regional volume deficits and symptom correlations. Design: Naturalistic study. Setting and Participants: Thirty neuroleptic-naive women with SPD and 29 female control subjects, both recruited from the community. Participants were group matched for age, parental socioeconomic status, handedness, and IQ. Interventions: A new segmentation method was applied to magnetic resonance images to automatically parcel the images into CSF, gray matter, and white matter. The neocortex was manually separated from subcortical and other nonneocortical structures. Voxel-based morphometry was applied to determine global and regional volume deficits. Main Outcome Measures: Left and right neocortical gray matter, white matter, and CSF relative volumes as well as clinical symptoms from the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire–Brief Version. Results: Smaller left (3.84%) and right (3.83%) neocortical gray matter relative volumes associated with larger left (9.66%) and right (9.61%) sulcal CSF relative volumes were found in women with SPD compared with controls. Voxel-based morphometry showed that the neocortical deficits in SPD were especially prominent in the left superior and middle temporal gyri, left inferior parietal region with postcentral gyrus, and right superior frontal and inferior parietal gyri. In the SPD group, larger lateral ventricle volumes correlated with more severe symptoms on the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire–Brief Version. Conclusions: The smaller neocortical gray matter volume and larger sulcal CSF volume provide evidence of the brain basis of this personality disorder and emphasize the communality of brain abnormalities in the schizophrenia spectrum.
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    Shape of caudate nucleus and its cognitive correlates in neuroleptic-naive schizotypal personality disorder
    (Elsevier BV, 2004) Levitt, James; Westin, Carl-Fredrik; Nestor, Paul; Estepar, Raul S.J; Dickey, Chandlee; Voglmaier, Martina; Seidman, Larry Joel; Kikinis, Ron; Jolesz, Ferenc; McCarley, Robert William; Shenton, Martha
    Background: We measured the shape of the head of the caudate nucleus with a new approach based on magnetic resonance imaging (MRI) in schizotypal personality disorder (SPD) subjects in whom we previously reported decreased caudate nucleus volume. We believe MRI shape analysis complements traditional MRI volume measurements. Methods: Magnetic resonance imaging scans were used to measure the shape of the caudate nucleus in 15 right-handed male subjects with SPD, who had no prior neuroleptic exposure, and in 14 matched normal comparison subjects. With MRI processing tools, we measured the head of the caudate nucleus using a shape index, which measured how much a given shape deviates from a sphere. Results: In relation to comparison subjects, neuroleptic never-medicated SPD subjects had significantly higher (more “edgy”) head of the caudate shape index scores, lateralized to the right side. Additionally, for SPD subjects, higher right and left head of the caudate SI scores correlated significantly with poorer neuropsychological performance on tasks of visuospatial memory and auditory/verbal working memory, respectively. Conclusions: These data confirm the value of measuring shape, as well as volume, of brain regions of interest and support the association of intrinsic pathology in the caudate nucleus, unrelated to neuroleptic medication, with cognitive abnormalities in the schizophrenia spectrum.
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    An elliptic PDE approach for shape characterization
    (IEEE, 2004) Haidar, H.; Bouix, Sylvain; Levitt, James; McCarley, Robert William; Shenton, Martha; Soul, Janet
    This paper presents a novel approach to analyze the shape of anatomical structures. Our methodology is rooted in classical physics and in particular Poisson's equation, a fundamental partial differential equation [1]. The solution to this equation and more specifically its equipotential surfaces display properties that are useful for shape analysis. We present a numerical algorithm to calculate the length of streamlines formed by the gradient field of the solution to this equation for 2D and 3D objects. The length of the streamlines along the equipotential surfaces was used to build a new function which can characterize the shape of objects. We illustrate our method on 2D synthetic and natural shapes as well as 3D medical data.