Functional Connectivity Analysis Applied to Brain Disorders
Wednesday 5 May 2010
Victoria Hall 16:00-18:00 Moderators: Nick F. Ramsey and Timothy L. Roberts

16:00 432.  

Mapping Threshold-Independent Drug Effects in Graph Theoretic Analyses of Functional Connectivity Networks:  the Opioid Analgesic Buprenorphine Preferentially Modulates Network Topology in Pain-Processing Regions
Adam J. Schwarz1,2, Jaymin Upadhyay2,3, Alexandre Coimbra2,4, Richard Baumgartner2,5, Julie Anderson2,3, James Bishop2,3, Ed George2,6, Lino Becerra2,3, David Borsook2,3
Translational Imaging, Eli Lilly and Company, Indianapolis, IN, United States; 2Imaging Consortium for Drug Development, Boston, MA, United States; 3PAIN Group, Brain Imaging Center, McLean Hospital, Belmont, MA, United States; 4Imaging, Merck, West Point, PA; 5Biometrics Research, Merck, Rahway, NJ, United States; 6Anesthesiology and Critical Care, Massachusetts General Hospital, Boston, MA, United States

Graph theoretic analyses of functional connectivity networks report on topological properties of the brain and may provide a useful probe of disease or drug effects. However, verifying node-wise effects over a range of binarization thresholds is inconvenient and often subjective for large, voxel-scale networks. We present a straightforward method for calculating graph theoretic node parameters that are robust to binarization threshold and suitable for image analysis in the study of functional connectivity. The method is applied to mapping drug modulation of localized functional network topology by the opioid analgesic buprenorphine in healthy human subjects.

16:12 433.  

High-Fat Diet Modulates Dopaminergic Network Activity: An Analysis of Functional Connectivity
Robert L. Barry1,2, Nellie E. Byun2,3, Jason M. Williams1,2, Michael A. Siuta4, Nicole K. Speed5,6, Christine Saunders5,6, Aurelio A. Galli4,5, Kevin D. Niswender4,7, Malcolm J. Avison1,2
Vanderbilt University Institute of Imaging Science, Nashville, TN, United States; 2Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States; 3Vanderbilt University Institute of Imaging Science, Nashville, TN, United States; 4Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, United States; 5Center for Molecular Neuroscience, Vanderbilt University, Nashville, TN, United States; 6Department of Pharmacology, Vanderbilt University, Nashville, TN, United States; 7Department of Medicine, Vanderbilt University, Nashville, TN, United States

Functional MRI was used to determine the effect of a 14-day high-fat diet on amphetamine-evoked dopaminergic neurotransmission and functional connectivity in rats in vivo.  High-fat diet blunted amphetamine-evoked activation in striatal and extrastriatal regions consistent with reduced dopamine transporter activity due to biochemically confirmed impaired insulin signaling.  Functional connectivity analysis revealed weakened inter-regional correlations with a high-fat diet, notably between accumbal-cingulate and striatal-thalamic regions.  These findings link high-fat diet with impaired dopamine transmission through central insulin resistance in areas subserving reward, motivation, and habit formation.

16:24 434

fMRI and Dynamic Causal Modeling Reveal Inefficient and Imbalanced Network Interactions in Developmentally Vulnerable Adolescents
Vaibhav A. Diwadkar1,2, Neil Bakshi1, Patrick Pruitt1, Ashu Kaushal3, Eric R. Murphy4, Matcheri S. Keshavan5, Usha Rajan3, Caroline Zajac-Benitez3

1Psychiatry & Behavioral Neuroscience, Wayne State University SOM, Detroit, MI, United States; 2Psychiatry, University of Pittsburgh SOM, Pittsburgh, PA, United States; 3Psychiatry, Wayne State University SOM, Detroit, MI, United States; 4Psychology, Georgetown University, Washington, DC, United States; 5Psychiatry, Beth Israel Deaconness Medical Center, Boston, MA, United States

We used fMRI and dynamic causal modeling to study altered functional organization of sustained attention networks in adolescent offspring of schizophrenia patients.  This group is at increased risk for psychiatric disorders, demonstrating impairments in cognitive function, making it an important one in whom to study developmental vulnerabilities.  Modeling focused on interactions between control systems such as the anterior cingulate cortex, and frontal, parietal and striatal regions.  Offspring evinced reduced cingulate-striatal coupling, but increased cingulate-prefrontal coupling.  Reduced cortico-striatal coupling, along with increased cortico-cortical coupling may reflect the impact of abnormal development on the role of control processes in the adolescent brain.

16:36 435.  

Short-Term Effects of Antipsychotic Treatment on Cerebral Function in Drug-Naive First-Episode Schizophrenia Revealed by RfMRI
Su Lui1, Tao Li, Wei Deng, Lijun Jiang, Qizhu Wu1, Hehan Tang1, Qiang Yue1, Xiaoqi Huang1, Raymond C. Chan2, David A Collier3, Shashwath A. Meda4, Godfrey Pearlson4, Andrea Mechelli3, John A. Sweeney5, Qiyong Gong1

1Huaxi MR Research Center, West China Hospital, Chengdu, Sichuan, China; 2Neuropsychology and Applied Cognitive Neuroscience Laboratory, Institute of Psychology, Bei Jin, China; 3Institute of Psychiatry King's College London, London, United Kingdom; 4Neuropsychiatry Research Center, Institute of Living, Hartford, United States; 5Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, IL, United States

Amplitude of low-frequency fluctuations in conjunction with the analysis of the resting state functional connectivity was applied to both regional cerebral function and functional integration in drug-naive schizophrenia patients before and after pharmacotherapy.  Thirty-four antipsychotic-naive first-episode schizophrenia patients and 34 age, sex, height, weight, handedness and years of education matched controls were scanned using an EPI sequence on a 3T MR imaging system. Patients were rescanned after six week¡¯s treatment.  For first time, we characterized that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied with decreased integration of function across widely distributed neural networks.

16:48 436.

Increased Local Connectivity in Children with ADHD
Suresh Emmanuel Joel1,2, Priti Srinivasan3, Simona Spinelli3,4, Stewart H. Mostofsky3,4, James J. Pekar1,2
Radiology, Johns Hopkins University, Baltimore, MD, United States; 2FM Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States; 3Laboratory for Neurocognitive and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, United States; 4Neurology, Johns Hopkins University, Baltimore, MD, United States

Resting state functional connectivity MRI performed on neurotypical children and children with attention deficit hyperactivity disorder (ADHD), revealed increased local connectivity of pre-supplementary motor area (an important atypically behaving neural substrate in rapid motor response inhibition tasks in ADHD) and increased local connectivity of the precunues (a locus of the default mode network) in children with ADHD. Local connectivity has been previously shown to decrease with age in TD children. Our results suggest a delay in this typical maturation process in children with ADHD.

17:00 437

Converging Results from Resting State and Task Response FMRI-Studies in ASD
Vesa Kiviniemi1, Jukka Rahko2, Xiangyu Long3, Jyri-Johan Paakki1, Jukka Remes1, Juha Nikkinen1, Tuomo Starck1, Irma Moilanen2, Mikko Sams4, Synnove Carlson5, Osmo Tervonen1, Christian Beckmann6, Yu-Feng Zang7
Diagnostic Radiology, Oulu University Hospital, Oulu, Finland; 2Child Psychiatry, Oulu University Hospital, Oulu, Finland; 3Max Planck Institute, Berlin, Germany; 4Lab. of Computational Engineering, Helsinki University of Technology, Helsinki, Finland; 5Brain Research Unit at AMI Center, Helsinki University of Technology, Helsinki, Finland; 6Clinical Neuroscience , Imperial College, United Kingdom; 7State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China

Resting state signal and GLM task activations were able to detect converging differences right anterior insula, visual cortex, S1 and IFG dominantly in right hemisphere. Background brain activity abnormality may intefere with task responses in these key regions of ASD.

17:12 438

Alterations of Brain Structure and Functional Connectivity in Chronic Cocaine Users
Hong Gu1, Xiujuan Geng1, Betty Jo Salmeron1, Thomas J. Ross1, Elliot A. Stein1, Yihong Yang1

1Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD, United States

Cocaine dependence is associated with various deficits in brain function, structure and metabolism. In this study, anatomic abnormalities and their relationship to functional network integrity in cocaine users were examined using voxel-based morphometry and resting-state functional connectivity analyses. Our data show that regions with reduced gray matter volume are closely associated with altered functional connectivity strength in corresponding brain networks.

17:24 439

Resting State Functional Connectivity in Patients with Periodic Hypersomnia
Maria Engström1, Thomas Karlsson2, Anne-Marie Landtblom3

1IMH/Radiological Sciences/CMIV, Linköping University, Linköping, Sweden; 2Behavioural Sciences and Learning/CMIV, Linköping University, Linköping, Sweden; 3IKE/Neurology/CMIV, Linköping University, Linköping, Sweden

Functional connectivity of intrisic fluctuations in the ‘resting brain’  was investigated in order to scrutinize the neuropathology of patients with periodic hypersomnia, Kleine-Levin syndrome (KLS). The main findings were that KLS patients exhibited increased coupling in the middle and inferior frontal gyri (Broca’s area) and decreased coupling in the left superior temporal gyrus (Wernicke’s area) as compared to healthy controls. In a previous study we showed working memory dysfunction accompanied by thalamic and left prefrontal hypoactivity in KLS. These findings suggest aberrant function in the thalamo-cortical networks, which might explain the patients’ symptoms.

17:36 440.

Altered Resting State Functional Connectivity in a Subthalamic Nucleus - Motor Cortex - Cerebellar Network in Parkinson’s Disease
Simon Baudrexel1,2, Torsten Witte1, Carola Seifried1, Frederic von Wegner3, Johannes C. Klein3, Helmuth Steinmetz3, Ralf Deichmann2, Rüdiger Hilker3

1Department of Neurology, University Hospital, Goethe University Frankfurt , Frankfurt am Main, Germany, Germany; 2Brain Imaging Center, Goethe University Frankfurt, Frankfurt am Main, Germany; 3Department of Neurology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany

It is well established that dopaminergic depletion as observed in Parkinson’s Disease (PD) alters metabolic and electrophysiological functional connectivity (FC) in large scale motor networks. Here we investigated FC of the subthalamic nucleus, a key player in PD-pathophysiology, using resting state fMRI and a common seed-voxel approach. We found significantly increased subthalamic FC to the primary motor cortex (PMC) in PD patients as compared to healthy controls. A subsequent seed-voxel analysis revealed increased FC between the left PMC and the bilateral cerebellum. The physiological and clinical relevance of this finding remains further to be determined.

17:48 441

Magnetic Resonance Imaging of Cerebral Electromagnetic Activity in Epilepsy
Padmavathi Sundaram1,2, William M. Wells2, Robert V. Mulkern1, Ellen J. Bubrick3, Edward Barry Bromfield3, Mirjam Münch4, Darren B. Orbach1,2

1Radiology, Children's Hospital, Harvard Medical School, Boston, MA, United States; 2Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; 3Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; 4Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States

We attempt to visualize an MR signal directly linked to neuronal activity. We hypothesized that reliable detection of an MR signal directly linked to neuronal activity in vivo, would be most likely under the following conditions: (i) fast gradient echo EPI, (ii) a cohort of epilepsy subjects, and (iii) concurrent EEG. Our subjects frequently experience high amplitude cortical electromagnetic discharges called interictal discharges. We found that these interictal spikes in the EEG of our subjects induced easily detectable MR signal changes. We refer to our technique as Encephalographic Functional Magnetic Resonance Imaging (efMRI).



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