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Biomedical subjects

Marek Kubicki

Publications and source records attributed to Marek Kubicki.

18 recordsLinked to original sources
PubMed2006

Attentional networks and cingulum bundle in chronic schizophrenia.

Thirty patients with chronic schizophrenia and 30 age-matched controls performed the Attention Network Test (ANT). A subset of the patient group (n=18) also had available magnetic resonance diffusion tensor imaging (DTI) measures of the cingulum bundle (CB) fractional anisotropy and volume. The patients showed a significantly different pattern of ANT performance, characterized primarily by decreased alerting efficiency. In addition, left CB fractional anisotropy correlated significantly with orienting of attention. Smaller right CB volume also correlated with reduced alertness, but not when covarying for medication and illness duration.

Adolescent↗
PubMed2006

Connectivity among semantic associates: an fMRI study of semantic priming.

Semantic priming refers to a reduction in the reaction time to identify or make a judgment about a stimulus that has been immediately preceded by a semantically related word or picture and is thought to result from a partial overlap in the semantic associates of the two words. A semantic priming lexical decision task using spoken words was presented in event-related fMRI and behavioral paradigms. Word pairs varied in terms of semantic relatedness and the connectivity between associates. Thirteen right-handed subjects underwent fMRI imaging and 10 additional subjects were tested in a behavioral version of the semantic priming task. It was hypothesized priming would be greatest, reaction time fastest, and cortical activation reduced the most for related word pairs of high connectivity, followed by related word pairs of low connectivity, and then by unrelated word pairs. Behavioral and fMRI results confirmed these predictions. fMRI activity located primarily in bilateral posterior superior and middle temporal regions showed modulation by connectivity and relatedness. The results suggest that these regions are involved in semantic processing.

Adult↗
PubMed2006

Fornix integrity and hippocampal volume in male schizophrenic patients.

BACKGROUND: The hippocampus has been shown to be abnormal in schizophrenia. The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia. METHODS: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. We used high spatial resolution magnetic resonance imaging (MRI) to measure hippocampal volume. RESULTS: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. D(m) was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean D(m) and reduced cross-sectional area of the fornix for patients. Patients also showed a significant correlation between reduced scores on neuropsychologic measures of declarative-episodic memory and reduced hippocampal volumes. CONCLUSIONS: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia.

Adult↗
PubMed2006

Smaller neocortical gray matter and larger sulcal cerebrospinal fluid volumes in neuroleptic-naive women with schizotypal personality disorder.

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.

Adult↗
PubMed2005

A review of diffusion tensor imaging studies in schizophrenia.

Both post-mortem and neuroimaging studies have contributed significantly to what we know about the brain and schizophrenia. MRI studies of volumetric reduction in several brain regions in schizophrenia have confirmed early speculations that the brain is disordered in schizophrenia. There is also a growing body of evidence suggesting that a disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, are responsible for the clinical symptoms and cognitive dysfunctions observed in this disorder. Thus an interest in white matter fiber tracts, subserving anatomical connections between distant, as well as proximal, brain regions, is emerging. This interest coincides with the recent advent of diffusion tensor imaging (DTI), which makes it possible to evaluate the organization and coherence of white matter fiber tracts. This is an important advance as conventional MRI techniques are insensitive to fiber tract direction and organization, and have not consistently demonstrated white matter abnormalities. DTI may, therefore, provide important new information about neural circuitry, and it is increasingly being used in neuroimaging studies of psychopathological disorders. Of note, in the past five years 18 DTI studies in schizophrenia have been published, most describing white matter abnormalities. Questions still remain, however, regarding what we are measuring that is abnormal in this disease, and how measures obtained using one method correspond to those obtained using other methods? Below we review the basic principles involved in MR-DTI, followed by a review of the different methods used to evaluate diffusion. Finally, we review MR-DTI findings in schizophrenia.

Anisotropy↗
PubMed2005

Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion tensor imaging study.

BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. CONCLUSIONS: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.

Adolescent↗
PubMed2005

Evidence for white matter abnormalities in schizophrenia.

PURPOSE OF REVIEW: The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is cast within the context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research. RECENT FINDINGS: White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely. This has come about as a result of advances in neuroimaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia. SUMMARY: Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia.

Journal Article↗
PubMed2005

The application of DTI to investigate white matter abnormalities in schizophrenia.

Schizophrenia is a serious and disabling mental disorder that affects approximately 1% of the general population, with often devastating effects on the psychological and financial resources of the patient, family, and larger community. The etiology of schizophrenia is not known, although it likely involves several interacting biological and environmental factors that predispose an individual to schizophrenia. However, although the underlying pathology remains unknown, it has been believed that brain abnormalities would ultimately be linked to the etiology of schizophrenia. This theory was rekindled in the 1970s, when the first computer-assisted tomography (CT) study showed enlarged lateral ventricles in schizophrenia. Since that time, there have been many improvements in MR acquisition and image processing, including the introduction of positron emission tomography (PET), followed by functional MR (fMRI), and diffusion tensor imaging (DTI). These advances have led to an appreciation of the critical role that brain abnormalities play in schizophrenia. While structural MRI has proven to be useful in investigating and detecting gray matter abnormalities in schizophrenia, the investigation of white matter has proven to be more challenging as white matter appears homogeneous on conventional MRI and the fibers connecting different brain regions cannot be appreciated. With the development of DTI, we are now able to investigate white matter abnormalities in schizophrenia.

Biomarkers↗
PubMed2004

An MRI study of spatial probability brain map differences between first-episode schizophrenia and normal controls.

We created a spatial probability atlas of schizophrenia to provide information about the neuroanatomic variability of brain regions of patients with the disorder. Probability maps of 16 regions of interest (ROIs) were constructed by taking manually parcellated ROIs from subjects' magnetic resonance images (MRIs) and linearly transforming them into Talairach space using the Montreal Neurological Institute (MNI) template. ROIs included temporal, parietal, and prefrontal cortex subregions, with a principal focus on temporal lobe structures. Subject Ns ranged from 11 to 28 for the different ROIs. Our global measure of the spatial distribution of the transformed ROI was the sum of voxels with 50% overlap among subjects. The superior temporal gyrus (STG) and fusiform gyrus (FG) had lower values for schizophrenic subjects than for normal controls, suggestive of greater spatial variability for these ROIs in schizophrenic subjects. For the computation of statistical significance of group differences in portions of the ROI, we used voxel-wise comparisons and Fisher's exact test. First-episode schizophrenic patients compared with controls showed lower probability (P < 0.05) at dorso-posterior areas of planum temporale and Heschl's gyrus, lateral and anterior regions in the left hippocampus (HIPP), and dorsolateral regions of fusiform gyrus. Importantly, most ROIs of schizophrenic subjects showed a significantly lower spatial overlap than controls, even after nonlinear spatial normalization, suggesting a greater heterogeneity in the spatial distribution of ROIs. There is consequently a need for caution in neuroimaging studies where data from schizophrenic subjects are normalized to a particular stereotaxic coordinate system based on healthy controls. Apparent group differences in activation may simply reflect a greater heterogeneity of spatial distribution in schizophrenia.

Adult↗
PubMed2004

White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study.

Hemisphere asymmetry was explored in normal healthy subjects and in patients with schizophrenia using a novel voxel-based tensor analysis applied to fractional anisotropy (FA) of the diffusion tensor. Our voxel-based approach, which requires precise spatial normalization to remove the misalignment of fiber tracts, includes generating a symmetrical group average template of the diffusion tensor by applying nonlinear elastic warping of the demons algorithm. We then normalized all 32 diffusion tensor MRIs from healthy subjects and 23 from schizophrenic subjects to the symmetrical average template. For each brain, six channels of tensor component images and one T2-weighted image were used for registration to match tensor orientation and shape between images. A statistical evaluation of white matter asymmetry was then conducted on the normalized FA images and their flipped images. In controls, we found left-higher-than-right anisotropic asymmetry in the anterior part of the corpus callosum, cingulum bundle, the optic radiation, and the superior cerebellar peduncle, and right-higher-than-left anisotropic asymmetry in the anterior limb of the internal capsule and the anterior limb's prefrontal regions, in the uncinate fasciculus, and in the superior longitudinal fasciculus. In patients, the asymmetry was lower, although still present, in the cingulum bundle and the anterior corpus callosum, and not found in the anterior limb of the internal capsule, the uncinate fasciculus, and the superior cerebellar peduncle compared to healthy subjects. These findings of anisotropic asymmetry pattern differences between healthy controls and patients with schizophrenia are likely related to neurodevelopmental abnormalities in schizophrenia.

Adult↗
PubMed2004

Comparison of single-shot echo-planar and line scan protocols for diffusion tensor imaging.

RATIONALE AND OBJECTIVES: Both single-shot diffusion-weighted echo-planar imaging (EPI) and line scan diffusion imaging (LSDI) can be used to obtain magnetic resonance diffusion tensor data and to calculate directionally invariant diffusion anisotropy indices, ie, indirect measures of the organization and coherence of white matter fibers in the brain. To date, there has been no comparison of EPI and LSDI. Because EPI is the most commonly used technique for acquiring diffusion tensor data, it is important to understand the limitations and advantages of LSDI relative to EPI. MATERIALS AND METHODS: Five healthy volunteers underwent EPI and LSDI diffusion on a 1.5 Tesla magnet (General Electric Medical Systems, Milwaukee, WI). Four-mm thick coronal sections, covering the entire brain, were obtained. In addition, one subject was tested with both sequences over four sessions. For each image voxel, eigenvectors and eigenvalues of the diffusion tensor were calculated, and fractional anisotropy (FA) was derived. Several regions of interest were delineated, and for each, mean FA and estimated mean standard deviation were calculated and compared. RESULTS: Results showed no significant differences between EPI and LSDI for mean FA for the five subjects. When intersession reproducibility for one subject was evaluated, there was a significant difference between EPI and LSDI in FA for the corpus callosum and the right uncinate fasciculus. Moreover, errors associated with each FA measure were larger for EPI than for LSDI. CONCLUSION: Results indicate that both EPI- and LSDI-derived FA measures are sufficiently robust. However, when higher accuracy is needed, LSDI provides smaller error and smaller inter-subject and inter-session variability than EPI.

Adult↗
PubMed2004

Neuropsychological correlates of diffusion tensor imaging in schizophrenia.

Patients with schizophrenia (n = 41) and healthy comparison participants (n = 46) completed neuropsychological measures of intelligence, memory, and executive function. A subset of each group also completed magnetic resonance diffusion tensor imaging (DTI) studies (fractional anisotropy and cross-sectional area) of the uncinate fasciculus (UF) and cingulate bundle (CB). Patients with schizophrenia showed reduced levels of functioning across all neuropsychological measures. In addition, selective neuropsychological-DTI relationships emerged. Among patients but not controls, lower levels of declarative-episodic verbal memory correlated with reduced left UF, whereas executive function errors related to performance monitoring correlated with reduced left CB. The data suggested abnormal DTI patterns linking declarative-episodic verbal memory deficits to the left UF and executive function deficits to the left CB among patients with schizophrenia.

Adolescent↗
PubMed2004

Method for combining information from white matter fiber tracking and gray matter parcellation.

We introduce a method for combining fiber tracking from diffusion-tensor (DT) imaging with cortical gray matter parcellation from structural high-spatial-resolution 3D spoiled gradient-recalled acquisition in the steady state images. We applied this method to a tumor case to determine the impact of the tumor on white matter architecture. We conclude that this new method for combining structural and DT imaging data is useful for understanding cortical connectivity and the localization of fiber tracts and their relationship with cortical anatomy and brain abnormalities.

Adult↗
PubMed2003

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study.

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.

Adult↗
PubMed2003

Spatial normalization of diffusion tensor MRI using multiple channels.

Diffusion Tensor MRI (DT-MRI) can provide important in vivo information for the detection of brain abnormalities in diseases characterized by compromised neural connectivity. To quantify diffusion tensor abnormalities based on voxel-based statistical analysis, spatial normalization is required to minimize the anatomical variability between studied brain structures. In this article, we used a multiple input channel registration algorithm based on a demons algorithm and evaluated the spatial normalization of diffusion tensor image in terms of the input information used for registration. Registration was performed on 16 DT-MRI data sets using different combinations of the channels, including a channel of T2-weighted intensity, a channel of the fractional anisotropy, a channel of the difference of the first and second eigenvalues, two channels of the fractional anisotropy and the trace of tensor, three channels of the eigenvalues of the tensor, and the six channel tensor components. To evaluate the registration of tensor data, we defined two similarity measures, i.e., the endpoint divergence and the mean square error, which we applied to the fiber bundles of target images and registered images at the same seed points in white matter segmentation. We also evaluated the tensor registration by examining the voxel-by-voxel alignment of tensors in a sample of 15 normalized DT-MRIs. In all evaluations, nonlinear warping using six independent tensor components as input channels showed the best performance in effectively normalizing the tract morphology and tensor orientation. We also present a nonlinear method for creating a group diffusion tensor atlas using the average tensor field and the average deformation field, which we believe is a better approach than a strict linear one for representing both tensor distribution and morphological distribution of the population.

Adult↗
PubMed2002

Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study.

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.

Adult↗
PubMedDate not supplied

Diffusion tensor imaging and its application to neuropsychiatric disorders.

Magnetic resonance diffusion tensor imaging (DTI) is a new technique that can be used to visualize and measure the diffusion of water in brain tissue; it is particularly useful for evaluating white matter abnormalities. In this paper, we review research studies that have applied DTI for the purpose of understanding neuropsychiatric disorders. We begin with a discussion of the principles involved in DTI, followed by a historical overview of magnetic resonance diffusion-weighted imaging and DTI and a brief description of several different methods of image acquisition and quantitative analysis. We then review the application of this technique to clinical populations. We include all studies published in English from January 1996 through March 2002 on this topic, located by searching PubMed and Medline on the key words "diffusion tensor imaging" and "MRI." Finally, we consider potential future uses of DTI, including fiber tracking and surgical planning and follow-up.

Anisotropy↗