Functional Connectivity: Clinical & Preclinical

Monday 12 May 2014      16:30 - 17:30

Space 1/Power Poster Theatre & Traditional Poster Hall 

Moderators: Gwenaëlle L. Douaud, Ph.D., Thomas T. Liu, Ph.D.

Click on this video icon to view the introductory session.

Francesco Sforazzini¹, Luca Dodero², Alberto Galbusera¹, Angelo Bifone¹, and Alessandro Gozzi^1
1MRI Laboratory, Istituto Italiano di Tecnologia, Centre for Neuroscience and Cognitive Sciences, Rovereto, Trento, Italy, ²Pavis Lab, Istituto Italiano di Tecnologia, Genova, Genova, Italy

Iinvestigations in healthy humans have highlighted an overall good correspondence between functional and structural connectivity. However, recent studies examining congenital or surgical alteration of the corpus callosum have produced conflicting results that challenge this view. Here we used high-resolution DTI and fMRI to probe structural and functional brain connectivity in BTBR mice, an acallosal strain widely used to mimic autism-like symptoms. We provide evidence of adaptive structural and functional cortico-cortical connectivity together with the presence of severely impaired antero-posterior and subcortical functional correlations. Our results highlight a complex region-dependent interplay between function and structure in congenital acollosal brains.

Alessandro Gozzi¹, Yang Zhan², Rosa C Paolicelli², Francesco Sforazzini¹, Alexei Vyssotski³, Angelo Bifone¹, and Cornelius Gross^2
1MRI Laboratory, Istituto Italiano di Tecnologia, Centre for Neuroscience and Cognitive Sciences, Rovereto, Trento, Italy, ²Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy, Roma, Italy, ³Institute of Neuroinformatics, University of Zürich and Swiss Federal Institute of Technology (ETH), Zurich, Zurich, Switzerland

Human fMRI studies have revealed impaired long-range functional connectivity in neuro-developmental disorders such as schizophrenia and autism. Deficits in the postnatal elimination of synapses (i.e. “pruning”), are thought to play an etiopathological role in these conditions. We used resting-state fMRI (rsfMRI) to test whether impaired synaptic maturation is sufficient to induce functional connectivity deficits. We found that Cx3cr1-KO mice, a line characterised by marked deficits in synaptic pruning, exhibit reduced long-range rsfMRI and LFP coherence in fronto-hippocampal areas. These results demonstrate that disruption in synaptic pruning is sufficient to produce connectional deficits reminiscent of those observed in human neurodevelopmental disorders

Fatima Nasrallah¹, Kavita Kaur D/O Ranjit Singh², Yeow Ling Yun², and Kai-Hsiang Chuang^2
1Clinical Imaging Research Center, Singapore, Singapore, Singapore, ²Singapore Bioimaging Consortium, Singapore, Singapore, Singapore

To understand the neurotransmission basis of resting-state functional connectivity, BOLD and EEG were measured when GABAA receptor system was antagonized by bicuculline. We found that inhibition of the GABAergic system in the brain increases both neural activity and functional connectivity. EEG shows intact neurovascular coupling and increased beta and gamma oscillation at resting state. This supports the neural basis and the role of inhibitory system on functional connectivity.

Disha Shah¹, Rafael Delgado y Palacios¹, Pieter-Jan Guns¹, Elisabeth Jonckers¹, Marleen Verhoye¹, and Annemie Van der Linden^1
1University of Antwerp, Bio-Imaging Lab, Wilrijk, Antwerp, Belgium

We hypothesize that synaptic transmission deficits in neurodegenerative disorders (ND) could be reflected as altered brain functional connectivity (FC) and can be detected using resting-state fMRI (rsfMRI). We investigate this hypothesis by pharmacologically modulating cholinergic synaptic transmission in the mouse brain using scopolamine and milameline. Scopolamine induced a decrease of FC between the hippocampus and thalamus and the hippocampus bilaterally, connections involved in learning/memory. The scopolamine-induced FC deficits are reversed by milameline. These results have implications for studies in animal models of ND, where rsfMRI can be used as a non-invasive tool to detect the modulation of synaptic transmission.

Matthew P Schroeder¹, Craig Weiss¹, Daniel Procissi², and John F Disterhoft^1
1Physiology, Northwestern University, Chicago, IL Illinois, United States, ²Radiology, Northwestern University, Chicago, IL Illinois, United States

Memory acquisition initially depends on the hippocampus but long-term memory resides in a distributed cortical network. This study characterized functional connectivity changes at sites mediating long-term memory. New Zealand White rabbits underwent trace eyeblink conditioning for ten days. Resting state scans were acquired following each session in a 7T Bruker MRI. Rabbits demonstrated greater hippocampal connectivity with HVI cerebellum, perirhinal cortex and thalamus and greater prefrontal connectivity with cholinergic basal forebrain after conditioning. Connectivity gradually and significantly changed as a result of learning a forebrain-dependent task. Future studies may identify additional regions showing connectivity changes as a result of learning.

Heather K. Decot¹, Yen-Yu Ian Shih^2,3, Wei Gao^2,4, Pranish Kantak⁵, Ian Jiang⁶, Karl Deisseroth⁷, Ilana B. Witten⁸, and Garret D. Stuber^1,9
1Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ²Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, NC, United States, ³Neurology, University of North Carolina at Chapel Hill, NC, United States, ⁴Radiology, University of North Carolina at Chapel Hill, NC, United States, ⁵Psychiatry, University of North Carolina at Chapel Hill, North Carolina, United States, ⁶University of North Carolina at Chapel Hill, NC, United States, ⁷Bioengineering, Stanford University, CA, United States, ⁸Psychology, Princeton University, Princeton, NJ, United States, ⁹Psychiatry, University of North Carolina at Chapel Hill, NC, United States

Here, we coupled optogenetic stimulation techniques with functional magnetic resonance imaging (fMRI) technology in an in vivo rat model to selectively activate dopaminergic neurons within the ventral tegmental area (VTA). This study demonstrates that transient optogenetic activation of DA neurons within the midbrain causes significant regional CBV increases in downstream targets of the VTA including the dorsal and ventral striatum. Future directions include exploring how DA neuromodulation promotes or suppresses functional connectivity within the intact brain.

Iris Y Zhou^1,2, Mengye Lyu^1,2, Russell W Chan^1,2, Y X Liang³, Adrian Tsang^1,2, K F So³, and Ed X Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China, ³Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China

Resting-state fMRI (rsfMRI) has shown potentials in revealing the functional plasticity after brain injury and training. Our previous study on a rat model of corpus callosotomy has demonstrated that disrupted rsfMRI connectivity can be partially restored atop the axonal connections as indispensable foundation. In this study, we further investigated the rsfMRI network reorganization after complete and partial callosotomy, aiming to identify the rewiring mechanism and topological alterations of rsfMRI networks if any. The results showed the restoration of disrupted interhemispheric connectivity may stem from the remodeling of intrahemispheric rsfMRI connectivity together with the remaining interhemispheric axonal pathways.

Hanbing Lu¹, William Rea¹, Leiming Wang¹, Elliot A Stein¹, and Yihong Yang^1
1National Institute on Drug Abuse, Baltimore, Maryland, United States

The physiological basis of resting state MRI (rsMRI) signal remains poorly understood. Several lines of evidence suggest the important role of spontaneous slow and infraslow EEG oscillation underlying the low-frequency BOLD fluctuations; Contrasting hypotheses emphasize the roles of higher frequency (gamma) activity. One approach to disentangle the relationship between electrophysiological and rsMRI signal is to investigate how evoked responses interact with ongoing spontaneous brain activity. We employ a whisker barrel cortex stimulation model to investigate this question. Our findings support the view that spontaneous activity in the delta band drives the rsMRI signal as manifested in functional connectivity.

Zhifeng Liang¹ and Nanyin Zhang^1
1Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, United States

Alterations of resting-state functional connectivity (RSFC) have been implicated in a wide range of psychiatric disorders. However, RSFC studies focusing on animal models of psychiatric disorders have been sparse, possibly due to confounding effects of widely used anesthesia in animal imaging. To bridge the gap between basic biomedical and human imaging research, in the present study we utilized the awake animal imaging approach established in our lab to evaluate an animal model of post-traumatic stress disorder. We revealed long-lasting impairment of RSFC within the amygdala-mPFC circuit and heightened anxiety level assessed by behavioral measurement after a single-episode predator odor exposure.

Chen-Yuan Kuo¹, Tsuo-Hung Lan¹, Changwei W. Wu², Kun-Hsien Chou³, Chun-Yi Lo³, and Ching-Po Lin^3
1Institution of Brain Science, National Yang-Ming University, Taipei, Taiwan, ²Graduate Institute of Biomedical Engineering, National Central University, Taoyuan, Taiwan, ³Institution of Neuroscience, National Yang-Ming University, Taipei, Taiwan

Schizophrenia is a complex mental illness, including the disorganize of thinking, behavior, and cognition. Recent study showed that functional abnormality of thalamus could be one of the underlying mechanisms in schizophrenia, and such conjecture can be further investigated using the resting-state fMRI technique. In this project, we examined the spectral distributions in the resting-state fMRI signals and conducted the comparison between schizophrenia patients and normal control. We discovered that spectral specificity exhibited in low-frequency oscillations of thalamus between the two groups, providing further evidence to study the functional alterations in schizophrenia.

Hesamoddin Jahanian¹, Thomas Christen¹, Michael E Moseley¹, and Greg Zaharchuk^1
1Stanford University, Department of Radiology, Stanford, California, United States

In an effort to investigate the effects of regional arterial arrival delays on identification of resting state functional connectivity networks, we studied the default mode network in a group of Moyamoya patients and compared it with normal healthy volunteers. We found that in the presence of significant delays, using standard seed-based method or independent component analysis (ICA), may lead to erroneous identification of functional connectivity networks. To solve this issue, we also propose a modified version of seed-based analysis method that accounts for the transit delays. Our results indicate that accounting for transit delays is crucial for analyzing the rsfMRI data in Moyamoya patients.

Eva Manzanedo¹, Alexandra Cristobal¹, Daniel García Frank¹, Elena Molina Molina², Ana Beatriz Solana^2,3, Norberto Malpica¹, Juan Álvarez-Linera⁴, and Juan Antonio Hernández Tamames^2,4
1Universidad Rey Juan Carlos, Móstoles, Madrid, Spain, ²CTB, Madrid, Spain, ³General Electric, Munich, Germany, ⁴Fundación Reina Sofía, Madrid, Spain

DMN functional connectivity differences between healthy subjects with significantly different normalized hippocampal volume (NHV) are analyzed in this work. Two groups of 25 subjects have been extracted out of the 632 subjects based on the NHV. A connectivity decrease in the DMN is statistically significant in the group of subjects with lower NHV. Considering that these subjects are more prone to develop AD, we have corroborated that DMN functional changes are an early biomarker for AD, which happen at the same time as structural changes, or maybe even before, because no structural changes in DMN areas have been appraised yet.

José Angel Pineda Pardo^1,2, Miguel Molina², Alexandra Cristobal², Eva Manzanedo², Francisco del Pozo¹, Juan Álvarez-Linera², and Juan Antonio Hernández-Tamames^2
1Laboratory of Neuroimaging, Center for Biomedical Technology, Pozuelo de Alarcón, Madrid, Spain, ²Laboratory of Neuroimaging, Fundación CIEN-Fundación Reina Sofía, Madrid, Madrid, Spain

Hippocampal atrophy is an early biomarker of Alzheimer's. According to this, we defined two groups of healthy elderly subjects with a normalized hippocampal volume (NHV) located at the top and bottom of the population distribution. We built structural networks using deterministic tractography and functional networks through fMRI correlations. The networks were compared between groups using a Wilcoxon test. In the higher NHV group we found higher anatomical connections between hippocampus and temporal cortices, and lower functional connections between entorhinal and cingulate cortices. The lower SC might be representative of an upcoming neurodegenerative process, being the higher FC a compensatory mechanism.

Karthik R Sreenivasan¹, Merida M Grant², Kimberly H Wood³, Muriah Wheelock³, Joshua R Shumen³, Richard C Shelton², David C Knight³, and Gopikrishna Deshpande^1,4
1AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, United States, ²Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, United States, ³Department of Psychology, The University of Alabama at Birmingham, Birmingham, AL, United States, ⁴Department of Psychology, Auburn University, Auburn, AL, United States

Although we know that presence of early life stress (ELS) modulates amygdala activity, it is unclear if the amygdala connectivity is affected and which amygdala nuclei cause these differences. In this study we perform effective connectivity analysis of fMRI data obtained from healthy controls with and without history of ELS. The analysis showed increased connectivity from right central nucleus and also enhanced amygdala connectivity in participants exposed to ELS. Our results showed intra- and extra- amygdaloid connectivity disruptions in the presence of ELS which could play a major role in understanding disorders caused by altered fear circuitry.

Ludovica Griffanti^1,2, Ottavia Dipasquale^1,2, Maria Marcella Laganà¹, Raffaello Nemni^1,3, Mario Clerici^1,3, Stephen Smith⁴, Giuseppe Baselli², and Francesca Baglio^1
1IRCCS, Fondazione don Carlo Gnocchi, Milano, Milan, Italy, ²Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy, ³Physiopatholgy Department, Università degli Studi di Milano, Milan, Italy, ⁴FMRIB (Centre for Functional MRI of the Brain), Oxford University, Oxford, United Kingdom

-An effective cleaning of resting state fMRI data should remove only inter-subject variability due to the artefacts, preserving the ability to capture between-subject variability of interest (e.g. healthy subjects vs patients). We compared four data-driven cleaning procedures on data relative to elderly healthy subjects and Alzheimer's disease (AD) patients, evaluating BOLD signal fluctuation reduction after cleaning and functional connectivity of the default mode network (DMN) on cleaned and uncleaned data. Our results showed that, among the tested methods, FMRIB’s ICA-based Xnoiseifier (FIX) was the most effective approach in detecting the typical DMN functional connectivity alterations in AD.