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. Schwarz^1,2, Jaymin Upadhyay^2,3, Alexandre Coimbra^2,4, Richard Baumgartner^2,5, Julie Anderson^2,3, James Bishop^2,3, Ed George^2,6, Lino Becerra^2,3, David Borsook^2,3
1Translational 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.

High-Fat Diet Modulates Dopaminergic Network Activity: An Analysis of Functional Connectivity
Robert L. Barry^1,2, Nellie E. Byun^2,3, Jason M. Williams^1,2, Michael A. Siuta⁴, Nicole K. Speed^5,6, Christine Saunders^5,6, Aurelio A. Galli^4,5, Kevin D. Niswender^4,7, Malcolm J. Avison^1,2
1Vanderbilt 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.

fMRI and Dynamic Causal Modeling Reveal Inefficient and Imbalanced Network Interactions in Developmentally Vulnerable Adolescents
Vaibhav A. Diwadkar^1,2, Neil Bakshi¹, Patrick Pruitt¹, Ashu Kaushal³, Eric R. Murphy⁴, Matcheri S. Keshavan⁵, Usha Rajan³, Caroline Zajac-Benitez^3
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.

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 Gong^1
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.

Increased Local Connectivity in Children with ADHD
Suresh Emmanuel Joel^1,2, Priti Srinivasan³, Simona Spinelli^3,4, Stewart H. Mostofsky^3,4, James J. Pekar^1,2
1Radiology, 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.

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 Zang^7
1Diagnostic 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.

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 Yang^1
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.

Resting State Functional Connectivity in Patients with Periodic Hypersomnia
Maria Engström¹, Thomas Karlsson², Anne-Marie Landtblom^3
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.

Altered Resting State Functional Connectivity in a Subthalamic Nucleus - Motor Cortex - Cerebellar Network in Parkinson’s Disease
Simon Baudrexel^1,2, Torsten Witte¹, Carola Seifried¹, Frederic von Wegner³, Johannes C. Klein³, Helmuth Steinmetz³, Ralf Deichmann², Rüdiger Hilker^3
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.

Magnetic Resonance Imaging of Cerebral Electromagnetic Activity in Epilepsy
Padmavathi Sundaram^1,2, William M. Wells², Robert V. Mulkern¹, Ellen J. Bubrick³, Edward Barry Bromfield³, Mirjam Münch⁴, Darren B. Orbach^1,2
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).