|MRI of Schizophrenia & Other Psychiatric Diseases|
A Novel Framework for Identifying DTI-Based
Brain Patterns of Schizophrenia
Peng Wang1, Ruben Gur1, Ragini Verma1
1Univ. of Pennsylvnia, Philadelphia, Pennsylvania, USA
Diffusion tensor imaging (DTI) provides rich information about brain tissue structure , especially white matter and has therefore gained attention in studying pathology of several diseases, such as schizophrenia, in a group-based analysis. In such research, it is important to accurately identify abnormal brain tissue that can classify patients and controls into two groups, for diagnosis, treatment and prognosis. However, conventional statistical methods are difficult to apply to DTI data due to its high dimensionality and nonlinearity. Most of the existing methods resort to a statistical t-test based on FA or kernel PCA features from tensors. However, the t-test usually assumes a single Gaussian distribution for each group, and a multivariate hypothesis testing is usually constrained by limited number of available samples and high-dimensional data. To address these issues, we present a novel group analysis framework in this paper. Rooted in the pattern classification theory, our method directly estimates the overlap between different groups using Bayes error rate. Unlike t-test, our method does not assume global Gaussian distribution for each group, but only considers data distribution to be locally smooth, thus facilitating separation of different groups when the data could have highly nonlinear structure, which is the case in DTI data. This framework also has the capability of combining multiple measurements that are extracted from tensor data, thus being able to handle multivariate testing. In this paper, the method is first used to identify abnormal brain regions that distinguish the patient group from control group, and is further validated by classifying patients from controls based on these regions. Experiments on 36 controls and 34 patients with schizophrenia show encouraging results.
Effects of Genetic Polymorphisms on White Matter Structure in
Schizophrenia Measured with Diffusion Tensor Imaging
Adam W. Anderson1, Mevhibe N. Tumuklu2, Lori R. Arlinghaus1, Tricia A. Thornton-Wells1, Xin Hong1, Herbert Y. Meltzer1
1Vanderbilt University, Nashville, Tennessee, USA; 2Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey
Diffusion tensor imaging was used to measure the variations in white matter structure related to single nucleotide polymorphisms (SNPs) in the histamine H1 receptor gene. Statistical parametric maps reveal regions of white matter where anisotropy depends strongly on SNP genotype. Hence, DTI can be used to map the effects of genotype on brain structure, thereby providing an 'intermediate phenotype' that may help to improve understanding of the relationships between genes and behavior.
Tract-Specific Anisotropy Measures and Temporal Characteristics of
David Matthew Carpenter1, Cheuk Tang1, Joseph I. Friedman1, 2, Hof R. Patrick, Daniel G. Stewart1, Monte S. Buchsbaum1, Philip D. Harvey1, Jack M. Gorman3, Kenneth L. Davis
1Mount Sinai School of Medicine, New York, New York, USA; 2Pilgrim Psychiatric Center, West Brentwood, New York, USA; 3Mount Comprehensive NeuroScience, Inc., White Plains, New York, USA
Here we implemented a fiber tracking algorithm and used it to investigate the temporal nature of white matter abnormalities in schizophrenia. Quantitative DTI tractography was used to quantify the fractional anisotropy (FA) of the forceps minor and the pyramidal tracts bilaterally. The tractography approach showed a significant decline in FA that was correlated with the duration of illness in the forceps minor. This FA decline in patients is beyond that accounted for by normal aging.
Improved Discriminant Analysis in Schizophrenia Using Fractional
Anisotropy and Apparent Diffusion Coefficient Images of Water Diffusion
Babak A. Ardekani1, 2, Jay Nierenberg1, 2, Debra DíAngelo1, Matthew J. Hoptman1, 2
1Nathan Kline Institute, Orangeburg, USA; 2New York University School of Medicine, New York, USA
The main objective of this study was to determine if using FA and ADC images concurrently in linear discriminant analysis (LDA) results in increased classification accuracy as compared to using FA or ADC alone. We scanned 42 patients with schizophrenia and 42 normal controls subjects. A two-dimensional LDA was performed following feature extraction using singular value decomposition. Specificity, sensitivity, and overall accuracy were respectively 85.7%, 71.4%, and 78.6% for ADC images alone, 88.1%, 73.8%, and 81.0% for FA images alone, and 90%, 76.2%, and 83.3% when both ADC and FA were used for classification. The results suggest that using multiple brain imaging measures may improve discrimination accuracy.
The Association of Cerebral Deficits with the Symptoms in Drug-NaÔve
First Episode Schizophrenia: An Optimized VBM and Resting Functional
Connectivity Study on 3T
Su Lui1, Xiaoqi Huang1, Wei Deng1, Hehan Tang1, Lijun Jiang1, Dongming Li1, Tijiang Zhang1, Xiuli Li1, Tao Li1, Qiyong Gong1, 2
1West China Hospital of Sichuan University, Chendu, People's Republic of China; 2University of Liverpool, Liverpool, UK
Optimized voxel based morphometry (VBM) in conjunction with the analysis of the resting state functional brain connectivity was applied to determine the relationship of the cerebral deficits with the symptoms in drug-naÔve first episode schizophrenia (FSE). 21 drug-naÔve FSE and 21 age, sex, height, weight, handedness and years of education matched controls were recruited, and were scanned using a volumetric 3D SPGR sequence and an EPI sequence on a 3T MR imaging system. For first time, we characterized that the symptoms of FSE associated with both the regional structural deficits and the functional networks.
Memory Consolidation in Schizophrenia and Its Relationship to Dentate
Gyrus and Cornu Ammonis Activity: FMRI Evidence
Vaibhav A. Diwadkar1, 2, Eric Murphy1, Simon B. Eickhoff3, Matcheri S. Keshavan1, 2
1Wayne State University SOM, Detroit, Michigan, USA; 2University of Pittsburgh SOM, Pittsburgh, Pennsylvania, USA; 3Forschungszentrum Juelich, Juelich, Germany
Schizophrenia is characterized in part by hippocampal related pathology. The hippocampus is the primary site in the brain for the initial consolidation of associative memories, and this process depends in part on NMDA receptor function. Schizophrenia is hypothesized to involve NMDA receptor hypofunction; therefore associative learning is an ideal paradigm using which to assess hippocampal function in the illness. We separately assessed changes in fMRI measured activity in the dentate gyrus and cornu ammonis sub-regions in the hippocampus during associative memory and demonstrate distinct patterns of pathological response in these sub-regions in schizophrenia.
Anterior Cingulate Glutamate is Greater During Low Relative to High
Dose Methadone Maintenance Dose in Heroin-Dependent Volunteers
Mark Greenwald1, Dalal Khatib1, Matcheri Keshavan1, Jeffrey Stanley1
1Wayne State University, Detroit, Michigan, USA
High-field short TE single-voxel 1H-MRS is used to determine in heroin-dependent subjects whether glutamate (GLU) levels in anterior cingulate cortex (ACC) and thalamus vary during within-subject manipulation of methadone maintenance dose. Subjects are first stabilized on high-dose methadone (scan 1), followed by reduction to a low dose (scan 2). All 6 completers in this ongoing study exhibit significantly lower GLU in ACC during high- vs. low-dose methadone. Heroin craving during high-dose methadone is positively correlated with change in ACC GLU during dose reduction. These findings are consistent with preclinical data and suggest new theoretical and therapeutic directions.
Basal Perfusion in Adolescents at Risk for Alcohol Use Disorders
Ai-Ling Lin1, David C. Glahn2, Ahmad R. Hariri3, Douglas E E. Williamson2
1University of Texas Health Science Center , San Antonio, Texas, USA; 2University of Texas Health Science Center, San Antonio, Texas, USA; 3University of Pittsburgh, Pittsburgh, Pennsylvania, USA
The purpose of this study was to investigate alterations in baseline cerebral blood flow (CBF) in adolescents at risk for alcohol use disorder (AUD). The baseline CBF was measured in both low- and high-risk groups for AUD using pulsed ASL sequence. Compare to the low-risk group, the high-risk group shows higher CBF in bilateral amygala and ventromedial prefrontal cortex but less CBF in bilateral insula and occipital cortex. These preliminary findings suggest that adolescents at relatively high-risk for AUD exhibit altered patterns of resting CBF in distributed corticolimbic regions supporting emotional behaviors.
An Investigation of the Microstructure of Brain Tissue in Social
Anxiety Disorder: A Turboprop-DTI Study
Anton Orlichenko1, K Luan Phan2, Huiling Peng1, Emil F. Coccaro3, Konstantinos Arfanakis1
1Illinois Institute of Technology, Chicago, Illinois, USA; 2University of Michigan, Ann Arbor, Michigan, USA; 3University of Chicago, Chicago, Illinois, USA
Social anxiety disorder, also known as social phobia, refers to long-lasting anxiety, extreme distress and impaired ability to function, caused by perceived social threats. It has in the past been correlated with hyperactivation of the amygdala, and hypoactivation of ventral frontal areas believed to provide cognitive regulation of the limbic system. The aim of this study was to use Turboprop diffusion tensor imaging to examine differences in white matter microstructure between patients with social phobia and healthy controls.
Localization of White Matter Transverse Relaxation
Time Abnormalities in Autism
Yann Gagnon1, Tim Devito1, Janet Hendry1, N Gelman1, N Rajakumar2, P Williamson2, R Nicolson2, Dick Drost1
1University of Western Ontario, Lawson Health Research Institute, London, Canada; 2University of Western Ontario, London, Canada
The transverse relaxation time (T2) is a quantitative parameter of magnetic resonance imaging which is indicative of the molecular environment in brain tissue. In this study, T2 times of the basal ganglia were evaluated in a group of Tourette Syndrome (TS) patients. Images obtained at 3 Tesla using the GESFIDE technique were spatially normalized for statistical analysis. TS patients were found to have increased T2 of the caudate nucleus when compared with controls.