Om Bhatt¹, Jed Meltzer¹, Bernhard Ross¹, and J. Jean Chen^1
1Rotman Research Institute, Baycrest, University of Toronto, Toronto, ON, Canada

Magnetoencephalography (MEG) is potentially valuable in clarifying the physiological mechanisms of resting-state fMRI-based functional connectivity. However, MEG and fMRI experiments cannot be performed simultaneously on the same subject. In this work, we present evidence for a stability of intrinsic brain activity across time. This stability is higher in certain brain regions, and higher during “eyes-open” than in “eyes-closed” resting state. These findings will enhance our ability to capitalize on the spatially resolved neuro-electric information from MEG to inform resting-state fMRI interpretations of brain activity. Future work will address the link between these spectral features and connectivity.

Han Yuan¹, Lei Ding^2,3, Min Zhu², and Jerzy Bodurka^1,4
1Laureate Institute for Brain Research, Tulsa, OK, United States, ²School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK, United States,³Bioengineering Center, University of Oklahoma, Norman, OK, United States, ⁴College of Engineering, University of Oklahoma, Norman, OK, United States

We describe a method to derive and characterize the resting state networks (RSNs) independently using EEG microstates. We combined electrophysiological source imaging and independent component analysis to obtain cortical sources of EEG microstates and compared them to the resting state networks independently derived from simultaneously measured BOLD fMRI. Our results revealed for the first time that the EEG-microstate-derived RSNs are of both high spatial similarity and temporal correlation with BOLD fMRI RSNs.

Catie Chang¹, Zhongming Liu², Michael C. Chen³, Xiao Liu², and Jeff H. Duyn^1
1Advanced MRI Section, LFMI, NINDS, National Institutes of Health, Bethesda, MD, United States, ²Advanced MRI Section, LFMI, NINDS, NIH, Bethesda, MD, United States,³Dept. of Psychology, Stanford University, Stanford, CA, United States

While resting-state functional connectivity (FC) has been observed to vary substantially over time-scales of seconds to minutes, the origins and relevance of these dynamics are not well understood. Here, we use simultaneous EEG-fMRI and a sliding-window analysis to investigate the electrophysiological correlates of within-scan fluctuations in FC between default-mode (DMN) and dorsal attention (DAN) networks. Fluctuations in alpha power were significantly correlated with fluctuations in DMN-DAN connectivity as well as in the degree of DMN-DAN anti-correlation. These results suggest an electrical signature of non-stationary DAN-DMN FC, potentially reflecting variations in vigilance or attentional states.

Mac Merritt¹, Garth Thompson¹, Wen-Ju Pan¹, Matthew E. Magnuson¹, and Shella Keilholz^1
1BMED, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States

This study uses simultaneous resting state fMRI and microelectrode recording to investigate the relationship between the temporal dynamics of bilateral electrical activity and bilateral blood oxygenation level dependent (BOLD) fluctuations using Sliding Window Correlation. This shows an electrical basis for BOLD signal functional connectivity dynamics that can be observed with sliding window correlation.

Omer Tal¹, Chi Wah Wong¹, Valur Olafsson¹, Mithun Diwakar², Roland Lee², Ming-Xiong Huang², and Thomas T. Liu^1,2
1Center for Functional MRI, University of California, San Diego, La Jolla, CA, United States, ²Radiology, University of California, San Diego, La Jolla, CA, United States

It has been previously shown that caffeine reduces resting-state BOLD connectivity throughout the brain. However, given the complex hemodynamic nature of the BOLD signal and caffeine’s effects on both neural activity and the vasculature, it was not clear whether neural or vascular factors were primarily responsible for the observed connectivity changes. In this study, we employ both fMRI and magnetoencephalography (MEG) to show that caffeine-induced reductions in BOLD connectivity reflect widespread decreases in neuro-electric connectivity.

Chi Wah Wong¹, Valur Olafsson¹, Omer Tal¹, and Thomas Liu^1
1Center for Functional MRI, University of California San Diego, La Jolla, CA, United States

The global signal is often considered a confound in resting-state fMRI. However, a recent primate study has shown that the global signal may contain significant contributions from neural sources. In this study, we used simultaneous EEG-fMRI to examine the sources of inter-subject variability in the amplitude of the global signal in humans. We found that the global signal amplitude is negatively correlated with an EEG-based vigilance measure.

Yury Koush^1,2, Maria Joao Rosa³, Fabien Robineau^4,5, Klaartje Heinen⁶, Nikolaus Weiskopf⁷, Patrik Vuilleumier^4,5, Dimitri Van de Ville^1,2, and Frank Scharnowski^1,2
1Department of Radiology and Medical Informatics, CIBM, University of Geneva, Geneva, Switzerland, ²Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Computer Science Department, University College London, London, United Kingdom, ⁴Department of Neuroscience, CMU, University of Geneva, Geneva, Switzerland, ⁵Geneva Neuroscience Center, Geneva, Switzerland, ⁶Institute of Cognitive Neuroscience, University College London, London, United Kingdom, ⁷Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, United Kingdom

Neurofeedback based on real-time fMRI is a novel technique that allows to train voluntary control over brain activity. So far, this technique was limited to training localized brain activity within a region of interest. Here, we overcome this limitation by presenting real-time dynamic causal modelling in order to provide neurofeedback information based on connectivity between brain areas rather than activity within a brain area. Being able to train network activity is an important extension of the neurofeedback approach that will contribute to its development as a promising research tool, and will open up a whole new range of medical applications.

David Clayton¹, Farshid Faraji¹, Douglas Arnold², Alex De Crespigny³, and Alexandre Coimbra^3
1Genentech, Inc., South San Francisco, California, United States, ²NeuroRX Research, Montreal, Quebec, Canada, ³Genentech Inc, South San Francisco, California, United States

Several single site resting-state fMRI studies (RS-fMRI) have shown that brain functional connectivity metrics are altered in Alzheimer Disease (AD) patients. Exploratory RS-fMRI was included in two global Phase II studies of a novel AD drug. We report here fMRI data quality control procedures and observed quality metrics from screening and very early on-treatment scans. Subject tolerance and protocol compliance was good. In spite of heterogeneous scanning equipment and variable raw SNR across sites, the data pre-processing pipeline resulted in consistent processed data quality metrics, with few scans that could not be used for subsequent functional connectivity analysis.

Jacco A. De Zwart¹, Peter van Gelderen¹, and Jeff H. Duyn^1
1Advanced MRI, LFMI, NINDS, National Institutes of Health, Bethesda, MD, United States

In low-noise situations the correlation between two signals is underestimated, an effect known as attenuation of correlation. This work shows that this well-established effect can lead to significant underestimation of cross-correlation in resting-state fMRI, where often the ratio between the neurogenic fluctuation of interest and noise level is less than 10. Correction of the cross-correlation value for this effect is well established and straightforward if the noise level is known.

Xiaolin Liu¹, B. Douglas Ward¹, Shi-Jiang Li¹, and Anthony G. Hudetz^2
1Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Self-organized criticality (SOC) is an attractive model for describing human brain dynamics. One of the most commonly sought empirical signatures of SOC is the power-law probability distributions in a complex system. This study proposes a novel algorithm that determines functional partitions (FPs) of the brain based upon both their anatomical and functional properties. We then show its effectiveness in demonstrating robust power-law distributions in healthy brains and discuss the implications of power-law manifestations in wake, anesthesia, and vegetative states as related to the maintenance and disruption the brain¡¯s self-organizing capability.

Shella Keilholz¹, Alessio Medda², Lukas Hoffmann³, Matthew E. Magnuson¹, Garth Thompson¹, and Wen-Ju Pan^1
1Biomedical Engineering, Emory/Georgia Tech, Atlanta, GA, United States, ²Georgia Tech Research Institute, Atlanta, GA, United States, ³Neuroscience Program, Emory University, Atlanta, GA, United States

While functional connectivity has typically been calculated over the length of an entire scan, interest has been growing in dynamic analysis methods that can detect changes in connectivity on much shorter time scales. Dynamic connectivity can be examined using sliding window correlation, but the properties of the dynamics depend on the window length, making a data-driven approach more attractive. We have developed an algorithm based on wavelet decomposition that clusters voxels into groups with similar temporal and spectral properties. The resulting clusters agree well with anatomy in the rat and the wavelet decomposition features exhibit sensitivity to network dynamics.

Xiao Liu¹ and Jeff H. Duyn^1
1Advanced MRI section, LFMI, NINDS, National Institutes of Health, Bethesda, MD, United States

To understand the negative correlation between resting-state fMRI signals and how it could be affected by global signal regression (GSR) procedure, a novel technique was applied to temporally decompose the default mode network (DMN) into multiple co-activation patterns (CAPs). This decomposition of activity patterns during rest suggests that anti-correlation between brain regions is not an artifact of global signal regression but may be caused by brief periods of negatively correlated neuronal activity.

Jingyuan Chen¹, Catie Chang², and Gary H. Glover^1,3
1Electrical Engineering, Stanford University, Palo Alto, CA, United States, ²National Institutes of Health, Bethesda, MD, United States, ³Radiology Department, Stanford University, Palo Alto, CA, United States

In the current study, we compared the spontaneous temporal behavior of the default-mode network (DMN) at rest and under a sustained 2-back working memory (WM) task load. Results indicated that during sustained WM task: (1) the spontaneous low-frequency temporal connectivity showed similar patterns as the steady-state task-induced activation/deactivation; (2) global variability with posterior cingulate cortex was weaker compared to rest; (3) the DMN and salience network showed significant power reduction compared to rest.

Farras Abdelnour¹, Henning Voss¹, and Ashish Raj^1
1Radiology, Weill Cornell Medical College, New York, NY, United States

We present a simple and intuitive network diffusion model which produces an accurate mathematical description of the structure-function relationship. We hypothesize that resting state functional relationships between brain regions result from this diffusion process applied to the structural network during rest. The network diffusion model applied to the structural networks closely predicts both the spatial and temporal correlation structures seen in the functional networks. We compare our work with published models. The proposed model is simple yet offers improved estimates of functional connectivity.

Kaundinya Gopinath¹, Simon Lacey², Shaheen Ahmed¹, Randall Stilla², and K. Sathian^2
1Department of Radiology & Imaging Sciences, Emory University, Atlanta, GA, United States, ²Department of Neurology, Emory University, Atlanta, GA, United States

The human occipitotemporal cortex (OTC) contains a number of regions specialized for processing particular types of sensory stimuli: including the lateral occipital complex (LOC), an object-selective area; the fusiform face area (FFA), a face-selective area; the parahippocampal place area (PPA), a scene-selective area; and the extrastriate body area (EBA), a body part-selective area. This study examined resting-state connectivity patterns of functionally localized LOC, EBA, FFA and PPA. Results indicate that regions of OTC exhibit both common and differential connectivity patterns. The EBA exhibited preferential connectivity with the default mode network, while FFA exhibited increased connectivity with the frontoparietal attention network.

Matthew E. Magnuson¹, Garth Thompson¹, Wen-Ju Pan¹, and Shella Keilholz^1
1Biomedical Engineering, Georgia Institute of Technology / Emory University, Atlanta, GA, United States

Dynamic analysis of functional MRI data is gaining traction over the traditional static based analysis, primarily because it provides complex information regarding the spatial and temporal properties of functional activity as opposed to a single average of those dynamic components. Majeed et al. previously published a technique for creating reproducible spatiotemporal dynamic templates from functional data based on a specified window length. In the work presented here we expand on the previous work using a bootstrapping algorithm to statistically threshold the template output allowing for quantification, clustering, and finally inter-subject comparisons.

I-Jung Chen¹, Yen-Hsiang Cheng², Tzu-Cheng Chao^1,2, Ping-Hong Lai^3,4, Fu-Nien Wang⁵, and Ming-Long Wu^1,2
1Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan, ²Institute of Medical Informatics, National Cheng Kung University, Tainan, Taiwan, ³Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ⁴School of Medicine, National Yang-Ming University, Taipei, Taiwan, ⁵Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

In general, fMRI analysis includes full spectral width (i.e., bandwidth) without looking into signal changes at different spectral frequency. For a resting-state fMRI (rsfMRI) experiment, low frequency oscillation (0.01 ¡V 0.1Hz) of MRI signals was reported to reveal activities of resting brain networks. In this study, we examined whether effective connectivity among resting brain networks changes at different frequency band. More specifically, conditional Granger Causality (GC) analysis was performed with band pass filtered time series of resting brain networks. The results show that effective connectivity varies in different frequency bands and outflows from each resting-state network present different frequency dependent characteristics.

Chia-Wei Li¹ and Jyh-Horng Chen^1,2
1Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, Taiwan, ²Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan, Taiwan

Recent researches pointed out that the cerebellum participates in many cognitive processes. In this study, we tried to parcel out the functional separation according to the functional connectivity between cerebellum and cerebrum based on one combined process of data-driven SVD and seed method. Moreover, we also parceled out the energy peaks in frequency domain among those cerebellar functional networks. In the result, fourteen functional patterns show that cerebellum participate in many cognitive processes, including of motor, executive control, memory, language, emotion, thalamic network, visuospatial, and DMN. And most of the energy peaks among those patterns distribute in 0.01~0.04 and 0.06~0.09 (Hz). It could provide one valuable reference for the further investigation about resting-state MRI.

Xiaoyun Liang¹, Alan Connelly^1,2, and Fernando Calamante^1,2
1Brain Research Institute, Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia, ²Department of Medicine, Austin Health and Northern Health, University of Melbourne, Melbourne, VIC, Australia

In this study, investigations on small-world network properties of ASL perfusion data have been conducted. The small-world network properties of ASL data are consistent with previous findings from BOLD data. Interestingly, the outcomes on the relationships between 4 specific network metrics and region-wise CBF demonstrate that consistent nonlinear patterns exist across normal subjects, which is well in line with the previous finding that ‘hub’ regions tend to have higher values for degree, vulnerability and centrality, but lower values for characteristic path length, along with higher metabolic energy consumption (and CBF). This should not only provide useful information to further our understanding of the metabolic energy consumptions with which the brain can maintain normal cognition with the lowest cost, but also have applications for clinical studies on brain disorders.

Ze Wang^1,2, Anish Mitra³, Marcus Raichle³, Anna Rose Childress¹, and John A. Detre^2,4
1Dept. of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Dept. of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ³Neurology, Washington University in St Louis, St. Louis, Missouri, United States, ⁴Dept. of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Entropy is a measure of system orderliness, and can be assessed as a quantitative brain status index. Using a large resting fMRI database, we systematically investigated resting brain entropy regarding its age and gender effects, spatial distribution, regional organization, and the hierarchical structure of local BEN communities. In this abstract, we showed high test-retest reproducibility of BEN mapping using resting state fMRI in the whole brain. We also showed a clear BEN contrast between the neocortex versus non-neocortex regions in the resting brain.

Jaemin Shin^1,2, Zhi Yang^3,4, Audrey Duarte⁵, and Xiaoping P. Hu^1
1Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA, United States, ²Center for Advanced Brain Imaging, Georgia Tech and Georgia State University, Atlanta, GA, United States, ³Institute of Psychology, Chinese Academy of Sciences, Beijing, China, ⁴National Institute of Mental Health, Bethesda, MD, United States,⁵School of Psychology, Georgia Tech, Atlanta, GA, United States

Recently, increased attention has been directed at resting-state functional connectivity. However, physiological fluctuations arising from respiratory and cardiac processes are detrimental in resting-state functional connectivity analysis. The present study aims to characterize the effects of physiological noise correction on the derived resting-state networks (RSNs). After correction, it is observed that the reproducibility of RSNs is increased. In particular, a technique that corrects for long-term physiological noise effects as well as short-term effects resulted in the highest reproducibility.

Ann S. Choe^1,2, Suresh E. Joel^3,4, Craig K. Jones^3,4, John Muschelli⁵, Visar Belegu^1,2, John W. McDonald^1,2, Brian S. Caffo⁵, Peter C.M. van Zijl^3,4, and James J. Pekar^3,4
1Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²International Center for Spinal Cord Injury, Hugo Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD, United States, ³Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴FM Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁵Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States

Understanding the intra-subject inter-session reproducibility of resting-state fMRI over prolonged time periods is essential. A longitudinal dataset of a healthy subject that covers the span of 128 weeks with weekly repeat measures was used to investigate the stability of network spatial distributions and between network connectivity (BNC), which were found to be stable over 128 weeks. This shows that rs-fMRI outcome measures can be used to reliably monitor disease progression and responses to therapeutic interventions. The most spatially stable network was the primary motor network and BNC was most stable between the secondary visual and salience networks.

Izabela Przezdzik¹, Andrew P. Bagshaw¹, and Stephen D. Mayhew^1
1BUIC, School of Psychology, University of Birmingham, Birmingham, United Kingdom

We used group ICA to identify the brain’s major bilateral networks and seed-based functional connectivity (FC) to demonstrate that some individual’s brains are more strongly connected than others. We observe that: 1) FC strength within a network is related to FC strength within other networks; 2) FC strength between networks can be predicted from the FC within the seed network; 3) FC within a cortical network is related to the strength of its connectivity with the thalamus. These results provide insight into the collaborative and antagonistic temporal relationships between the networks which form the functional architecture of the human brain.

Hsiao-Ying Wey^1,2, Kimberly A. Phillips^1,3, Angela R. Laird¹, Peter Kochunov^1,4, Michael D. Davis¹, David C. Glahn^1,5, John Blangero⁶, Timothy O. Duong⁷, and Peter T. Fox^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Athinoula A. Martinos Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States, ³Department of Psychology, Trinity University, San Antonio, TX, United States,⁴Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD, United States, ⁵Department of Psychiatry, Yale University, Hartford, CT, United States,⁶Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, United States, ⁷Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, TX, United States

We aim to investigate evolutionary differences of functional connectivity between humans and nonhuman primates. Specifically, we identified resting-state intrinsic connectivity networks in four primate species (humans, chimpanzees, baboons, and capuchin monkeys) spanning different levels of the evolutionary tree, and we compared similarities and discrepancies of those networks found in humans. We observed similar networks associated with primary functions in both species. Interestingly, all nonhuman primate species displayed lateralized functional networks that were strikingly similar to those observed in humans.

Zhixin Li¹, B. Douglas Ward², Melinda R. Dwinell³, and Christopher P. Pawela^1
1Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI, United States, ²Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ³Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, United States

We address for the first time the genetic influences on intrinsic neural connectivity in a resting-state fMRI study of two genetically different inbred rat strains:Brown Norway(BN) and Dahl salt-sensitive(SS) rats.SS rat exhibited differential intrinsic functional connectivity patterns in primary somatosensory and caudate putamen network in comparison to BN rats. These task-specific regional differences in neural network can speculatively suggest an “endophenotype” or imaging marker of genetic component of under specific biological events.

Laura-Adela Harsan¹, Anna Mechling¹, Neele Hübner¹, Hsu-Lei Lee¹, Jürgen Hennig², and Dominik von Elverfeldt^1
1Medical Physics, University Medical Center, Freiburg, BW, Germany, ²Medical Physics, University Medical Center Freiburg, Freiburg, BW, Germany

The intrinsic connectional architecture of functional networks (FN) in the mouse brain remains a significantly underexplored research area. The primary goal of our study is to systematically and comparatively probe using resting state fMRI (rsfMRI) the intrinsic brain functional connectivity of two mouse strains, intensively used in the fundamental and preclinical neuroscience: the C57Bl6/N and the Balbc/J strain. Using Independent Component Analysis (ICA), partial correlation and graph theory, we identify the relevant, influential nodes in each strain and show inter-strain differences in the large scale organization of FN.

Hesamoddin Jahanian¹, Wendy W. Ni¹, Thomas Christen¹, Manjula K. Tamura², Michael E. Moseley¹, and Greg Zaharchuk^1
1Department of Radiology, Stanford University, Stanford, California, United States, ²Division of Nephrology, Stanford University, Stanford, California, United States

Spontaneous fluctuations in blood oxygenation level dependent (BOLD) signal have been observed in resting state time series measurements. Although their precise physiological origin is not yet clear, they are likely to arise from oscillations in metabolic-linked brain physiology, arterial vasomotion and hemodynamics. We hypothesized that these physiological fluctuations may reveal cerebrovascular autoregulatory mechanisms and consequently be associated with factors modulating the cerebrovasculature such as aging and hypertension. To test this hypothesis, we compared the magnitude of spontaneous BOLD fluctuations in two populations: 1) young healthy adults and 2) hypertensive elderly subjects with chronic kidney disease (CKD).

Nadja Razavi¹, Andrea Federspiel¹, Thomas Dierks¹, Martinus Hauf², and Kay Jann^1
1Dept. of Psychiatric Neurophysiology, University Hospital of Psychiatry / University of Bern, Bern, Bern, Switzerland, ²Institut of Diagnostic and Interventional Neuroradiology, University of Bern / Inselspital, Bern, Bern, Switzerland

We measured resting-state DMN activity by pCASL based cerebral blood flow (CBF) and BOLD fMRI data in 11 patients with schizophrenia. We show that both datasets yield spatially similar DMN components and we demonstrate that the spatial similarity of a patient’s CBF-DMN to the respective DMN group component was negatively correlated to the PANSS positive score. In addition, pCASL provides information about the absolute perfusion of the brain and network: Increased CBF in patient’s DMNs (controlled for grey matter CBF), suggested a state of hyperactivity that may be relating to processing errors occurring in schizophrenia.

Emily S. Finn¹, Xilin Shen², John M. Holahan³, Xenophon Papademetris^2,4, Dustin Scheinost⁴, Cheryl Lacadie², Sally E. Shaywitz³, Bennett A. Shaywitz³, and Robert Todd Constable^2,4
1Interdepartmental Neuroscience Program, Yale University, New Haven, CT, United States, ²Diagnostic Radiology, Yale University, New Haven, CT, United States, ³Yale Center for Dyslexia and Creativity, Yale University, New Haven, CT, United States, ⁴Biomedical Engineering, Yale University, New Haven, CT, United States

We applied a novel data-driven functional connectivity (FC) analysis to fMRI data from dyslexic vs. non-impaired readers to reveal functional subnetworks involved in successful reading. Our method improves upon previous FC analyses by not requiring a priori seed regions or arbitrary thresholds to determine connectivity. We found a network of occipitoparietal (visual association) and frontal (attention) areas that were better connected in non-impaired readers, suggesting that these subjects are better able to process word shapes and modulate their attention to visual stimuli. We believe this method can be extended to examine differentially connected functional subnetworks in other neural disorders.

Xiawei Ou¹, George Andrew James², Zhaohua Ding³, Charles M. Glasier¹, Raghu H. Ramakrishnaiah¹, and Jeffrey R. Kaiser^4
1Radiology, Arkansas Children's Hospital; University of Arkansas for Medical Sciences, Little Rock, AR, United States, ²Brain Imaging Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, United States, ³Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ⁴Pediatrics, Arkansas Children's Hospital; University of Arkansas for Medical Sciences, Little Rock, AR, United States

We performed resting state fMRI study on extremely low birth-weight (ELBW) infants randomized to groups with or without permissive hypercapnia and compared the functional connectivity in the brain to the primary visual cortex. We found decreased inter-network functional connectivity between visual cortex and motor cortex for the hypercapnic infants. Our findings suggest that hypercapnic ventilation may reduce functional connectivity between brain default networks.

Raag D. Airan¹, Joshua Vogelstein^2,3, Brian S. Caffo⁴, James J. Pekar^1,5, and Haris I. Sair^1
1Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MARYLAND, United States, ²Statistical Sciences, Duke University, Durham, NC, United States,³Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MARYLAND, United States, ⁴Biostatistics, Johns Hopkins University, Baltimore, MARYLAND, United States,⁵F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MARYLAND, United States

Resting state fMRI (rs-fMRI) has received much recent attention as a complement to task-based fMRI. While reproducibility of rs-fMRI has been well established at the group level, individual subject level analysis is desired for most clinical applications and is less well characterized. Here we establish the reproducibility of subject-level rs-fMRI data and determine that 7 minutes is sufficient to acquire the maximal rs-fMRI information for differentiating individual subjects. We see strong reproducibility of individual subject data with only 1 minute of acquisition time. Additionally, we find that brain regions yielding the most individual differentiation correspond to higher cortical processing centers.

Valur Olafsson¹, Chi Wah Wong¹, Markus Plank², Joe Snider², Eric Halgren³, Howard Poizner², and Thomas Liu^1
1Center for Functional MRI, UCSD, La Jolla, CA, United States, ²Institute for Neural Computation, UCSD, La Jolla, CA, United States, ³Multimodal Imaging Laboratory, UCSD, La Jolla, CA, United States

Learning without feedback is often referred to as unsupervised learning. Prior work suggests that structures in the basal ganglia have a role in unsupervised learning performance. In this study we ran a resting state fMRI study on 10 subjects that had gone through an unsupervised learning task in a complex virtual reality environment and had been assessed on their performance to learn without feedback. We found that there was significant correlation between the performance measures and resting-state fMRI measures from basal ganglia structures. Our results indicate that resting-state measures could be used to predict individual differences in unsupervised learning.

Huijin Song¹, Jeehye Seo¹, Seonguk Jin¹, Moon Han¹, Moonjung Hwang², Yongmin Chang^1,3, and Kyung Jin Suh^4
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, ²GE healthcare, Seoul, Korea, ³Molecular medicine, Kyungpook National University, Daegu, Korea,⁴Radiology, School of Medicine, Dongguk University, Gyungju, Korea

In the last decades, a few studies showed that the independent component (IC), which extracted from task based fMRI data by independent component analysis (ICA) method, is very similar with the task-evoked brain network. However, previous researchers did not attempt to identify other ICs possibly reflecting brain networks, which were implicitly associated with the task. Therefore, in this study, we aimed to identify not only IC reflecting motor network but also ICs reflecting neural network implicitly involved with alternative finger tapping task using ICA. Furthermore, we also investigated the relation between the temporal patterns of identified ICs and the hemodynamic response of finger tapping task to evaluate the possible difference in the temporal patterns of identified ICs between welders with chronic manganese exposure and healthy controls. Based on our finding that ICA could identify not only IC reflecting motor network but also ICs reflecting neural network implicitly involved with alternative finger tapping task. In addition, the strong correlation of IC reflecting WM with hemodynamic response of alternative finger tapping task suggest that welders required more WM resource for successful complex motor task due to WM deficit.

Kaundinya Gopinath¹, Simon Lacey², Shaheen Ahmed¹, Randall Stilla², and K. Sathian^2
1Department of Radiology & Imaging Sciences, Emory University, Atlanta, GA, United States, ²Department of Neurology, Emory University, Atlanta, GA, United States

The human occipitotemporal cortex (OTC) contains a number of regions specialized for processing particular types of sensory stimuli: including the lateral occipital complex (LOC), the fusiform face area (FFA), the parahippocampal place area (PPA), and the extrastriate body area (EBA), exhibiting selectivity for objects, faces, scenes and body-parts, respectively. This study examined functional connectivity patterns of functionally localized LOC, EBA, FFA and PPA, during rest and from residuals of OTC localizer fMRI data. Results indicate increased OTC functional connectivity (in the residuals data) to frontoparietal attention network during visual processing compared to rest, reflecting the attention demands of the task.

Chunxiang Jiang¹, Yanjun Diao¹, Xiaojing Long¹, Weiqi Liao¹, and Lijuan Zhang^1
1Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China

Circadian rhythm of sleep and wakefulness is a fundamental property of human physiology, which is important for sustaining essential body functions. Brain physiology varies according to the rhythm. In this study, we used ReHo(Regional Homogeneity) method to investigate the diurnal changes of neural activity in normal human brain in resting state.

Tynan Stevens^1,2, Steven Beyea^1,2, Ryan D'Arcy³, Tim Bardouille², and David Clarke^1,4
1Dalhousie University, Halifax, Nova Scotia, Canada, ²NRC, Halifax, Nova Scotia, Canada, ³Frasier Health Authority, Surrey, British Columbia, Canada, ⁴Neurosurgery, Capital District Health, Halifax, Nova Scotia, Canada

Functional brain imaging must demonstrate precise functional localization for application to presurgical planning. We investigated two leading candidate technologies - fMRI and MEG - in this context. We implemented a simple grip-force task that has been shown to predominately activate the primary motor region. We evaluated localizing ability using several metrics, including peak activation magnitude (within an anatomically defined ROI), activation extent, laterality, anatomical specificity, and reliability of activated regions. We found that similar peak activation magnitude, lateralization, and reliability could be achieved with either modality. However, fMRI had advantages in terms of specificity to our anatomically defined ROIs.

Javier Gonzalez-Castillo¹, Daniel A. Handwerker¹, Colin Hoy¹, and Peter A. Bandettini^1
1Section on Functional Imaging Methods, National Institute of Mental Health, Bethesda, MD, United States

The sensitivity of BOLD fMRI heavily depends on temporal signal-to-noise ratio (TSNR) and versatility of the hemodynamic response model. Recent work demonstrated that with optimal TSNR and using a sufficiently versatile response model it is possible to detect wide spread activations all over the brain in response to a relatively simple visual stimulation plus attention control task using a 3T scanner and 3.75x3.75x3.8mm3 voxels. Here we extent that work on a 7T scanner to evaluate the tissue specificity of high TSNR activations and the effect of higher field strength.

Jürgen Finsterbusch^1,2, Christian Sprenger^1,2, and Christian Büchel^1,2
1Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, ²Neuroimage Nord, Hamburg-Kiel-Lübeck, Germany

Important basic functions of the central nervous system like sensory processing, motor execution or reflexes involve the spinal cord. To investigate the functional relationship between the brain and the spinal cord directly, fMRI acquisitions covering both regions in the same experiment are required. But the demands differ considerably between the two regions, in particular regarding the shim adjustment. With different fields-of-view, in-plane resolutions, and slice thicknesses and using a dynamic coil selection and update of the linear shim terms, combined T2*-weighted acquisitions of the brain and the cervical spinal cord are feasible as is demonstrated in healthy volunteers at 3T.

Robert L. Barry^1,2, John C. Gore^2,3, and Seth A. Smith^1,2
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ³Vanderbilt University, Nashville, TN, United States

Functional imaging of the human spinal cord (spinal fMRI) has been demonstrated by a handful of groups worldwide, and can detect changes in spinal function due to injury and multiple sclerosis. However, to date there have been no reports of human spinal fMRI at any field strength above 3 Tesla. The proposed multi-shot pulse sequence and post-processing methods are designed to obviate or mitigate challenges of ultra-high-field fMRI that include tissue heating (specific absorption rate), T2* blurring, and geometric distortions. To the best of our knowledge, this abstract is the first published demonstration of human spinal fMRI at 7 Tesla.

Paul Summers¹, Armando Bauleo¹, Fabiola Cretti², Fausta Lui¹, and Carlo Adolfo Porro^1
1University of Modena and Reggio Emilia, Modena, MO, Italy, ²Ospedali Riuniti di Bergamo, Bergamo, BG, Italy

We examined short-echo time, 3D turbo-spin echo (TSE) sequences with and without blood-signal nulling for functional contrast that may that compete with vascular space occupancy (VASO) effects. Subjects performed a blocked, self-paced left-hand finger tapping task during acquisition of the images. Functional responses in nearly identical spatial locations were seen that correlated negatively with task performance in the blood.nulled case and positively otherwise. These preliminary results suggest that short echo time, 3D TSE is sensitive to functional signal changes, but do not distinguish between possible sources such as VASO; BOLD; SEEP or inflow in the absence of blood nulling.

Albert Kir^1,2, Alan B. McMillan³, Rao P. Gullapalli^1,2, and Joel M. Morris^4
1Magnetic Resonance Research Center, University of Maryland, School of Medicine, Baltimore, MD, United States, ²Diagnostic Radiology and Nuclear Medicine, University of Maryland, School of Medicine, Baltimore, MD, United States, ³Radiology, University of Wisconsin Madison, School of Medicine and Public Health, Madison, WI, United States,⁴Communication and Signal Processing Laboratory, University of Maryland, Baltimore County, Baltimore, MD, United States

Echo Planar Imaging (EPI) techniques have been traditionally used to perform functional magnetic resonance imaging (fMRI). Due to the issues of signal dropout and/or geometric distortion of EPI-based sequences, balanced steady-state free precession (bSSFP) techniques have been studied as a potential alternative for acquiring fMRI images with improved image signal and spatial resolution. However, depending on the distribution of field inhomogeneity, a bSSFP sequence exhibits geometrically-varying sensitivity to the BOLD signal. In this study, we have implemented a frequency modulated (FM) bSSFP approach to address this issue and demonstrate its application in high-resolution fMRI.

Tiffany Jou¹, Steve Patterson², John M. Pauly¹, and Chris Bowen^2
1Electrical Engineering, Stanford University, Stanford, California, United States, ²Institute for Biodiagnostics (Atlantic), National Research Council Canada, Halifax, Nova Scotia, Canada

Results from a rat hypercapnia study suggests that by using RF catalyzation to alternate between two RF phase-cycling steady states, whole-brain BOLD activation from a single run of the functional paradigm is possible. This approach has been coined “alt-SSFP”. Our overall goal was to investigate these possibilities in human studies for the first time. Using human breath holding experiments to perturb BOLD signal, we have shown that alt-SSFP (1) recovers functional sensitivity in regions that suffer signal dropout in GRE-EPI, and (2) exhibits functional sensitivity comparable to the pbSSFP two-acquisition method, but using just a single functional run.

Ute Goerke¹, Craig Moodie², Krista Wisner², and Angus MacDonald III^2
1CMRR, University of Minnesota, Minneapolis, Minnesota, United States, ²Psychology, University of Minnesota, Minneapolis, Minnesota, United States

As previously reported RASER provides excellent fMRI activation maps in the orbitofrontal cortex (OFC) in humans without suffering from the typical blurring and signal loss of echo-planar images due to magnetic field variations near air-tissue interfaces. In the presented work, a novel 2D parallel imaging approach for RASER is implemented to achieve whole brain coverage with acceptable spatiotemporal resolution for fMRI. In order to demonstrate that the ability to detect activation near air cavities with accelerated RASER is retained a 7 T fMRI study was performed using a working memory task modulated with gains and losses showing reliable activation in the OFC.

Michael Germuska¹ and Daniel P. Bulte^1
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, United Kingdom

BOLD mediated vessel size imaging (VSI) is preformed in the brainstem. Two different acquisition strategies, dual-echo and multi-echo EPI (MESSER), are compared with and without cardiac gating. The dual-echo acquisition scheme is found to outperform the multi-echo strategy. Both gated acquisitions show an improved performance, as measured by VSI fitting residuals, compared to non-gated acquisitions. The robust performance and small fitting residuals of the gated dual-echo sequence suggests it can be a useful tool for assessing vascular changes in the brainstem.

Jeroen Cornelis Willem Siero^1,2, Dora Hermes^1,3, Hans Hoogduin², Peter R. Luijten², Nick F. Ramsey¹, and Natalia Petridou^1,2
1Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Radiology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands,³Stanford University, Stanford, California, United States

BOLD fMRI has the potential to map activation patterns of small neuronal ensembles such as columns. However, to confirm whether BOLD activation maps reflect the underlying neuronal activity patterns, a comparison with electrophysiological data is required. Here, we investigate the spatial representation of finger movements using electrocorticography (ECoG) post-implant and presurgical BOLD fMRI at 7T in the same human subjects. We show that BOLD and high frequency ECoG maps are closely matched; movement of three individual fingers could be distinguished on a spatial span of 12 mm. These results are promising for the spatial correspondence between neuronal and vascular responses.

M. Muge Karaman¹, Iain P. Bruce¹, and Daniel B. Rowe^1,2
1Department of Mathematics, Statistics, and Computer Science, Marquette University, Milwaukee, WI, United States, ²Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

In fMRI, the voxels in gray matter (GM) contain neurons that are to be active while performing a task. We develop a model to determine brain activation by incorporating T₁and T₂^* of GM. The model considers the physical nonlinear signal equation to model MR magnetization rather than using a linear model; utilizes the first scans of the complex-valued fMRI data to estimate each voxel’s T₁ and T₂^*; and incorporates GM T₁ and T₂^* values into the activation statistics. It has been found that the proposed model provides more significant activation statistics compared to the commonly used fMRI activation models.

Peiying Liu¹, Chandramallika Basak², and Hanzhang Lu^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Center for Vital Longevity, University of Texas at Dallas, Dallas, Texas, United States

Given that the BOLD signal is an indirect measure of neural activity, there have been great efforts recently developing more quantitative fMRI methods, including fMRI normalization using cerebrovascular reactivity. In this work, we compared between the plain BOLD signal and the BOLD signal after normalization with cerebrovascular reactivity. We found the normalized fMRI signal showed a significant correlation with working memory performance across healthy individuals, while the plain BOLD signal showed no correlation. This work provided the first direct evidence that quantitative measure of brain activation after accounting for vascular factors can provide a more accurate predictor of cognitive function.

Marta Re^1,2, Tommaso Piccoli^3,4, Giancarlo Valente³, Vincent Van De Ven³, Alexander Sack³, and Francesco Di Salle^3,5
1IRCCS Istituto Scientifico “Eugenio Medea”, Bosisio Parini, Lecco, Italy, ²Dipartimento di Bioingegneria, Politecnico di Milano, Milano, MI, Italy, ³Department of Cognitive Neuroscience, University of Maastricht, Maastricht, Limburg, Netherlands, ⁴Dipartimento di Biomedicina e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, PA, Italy, ⁵Dipartimento di Medicina e Chirurgia, Università di Salerno, Baronissi, SA, Italy

Working memory (WM) load has effects on regional neural activation, but the mechanism through which its modulates brain connectivity is still unclear. Spatial independent component analysis (ICA) is a reliable technique to investigate the networks during an fMRI task. The aim of this work is to use the time course of the WM task involved networks (default mode network and working memory network), selected by means of ICA, for studying: a) how these networks are involved with the complexity of the task and the phase; b) how, in these networks, complexity and phase are correlated with reaction times.

Lalit Gupta¹, René M.H. Besseling^2,3, Geke M. Overvliet^2,4, Paul A.M. Hofman^2,4, Anton de Louw², Maarten Vaessen^2,3, Albert P. Aldenkamp^2,4, Shrutin Ulman¹, Jacobus F.A. Jansen^3,4, and Walter H. Backes^3,4
1Philips Electronics India Ltd., India, ²Epilepsy center Kempenhaeghe, Heeze, Netherlands, ³Research School for Mental Health & Neuroscience, Maastricht University, Netherlands, ⁴Maastricht University Medical Center, Maastricht University, Netherlands

In many brain diseases it has been observed that spatial patterns in BOLD activation maps appear more (diffusively) distributed than in healthy controls. However, measures that can quantitatively characterize this spatial distributiveness in individual subjects are lacking. We evaluated language activation maps by applying a number of conceptually different spatial heterogeneity measures of activation distribution patterns. For a language task that showed no systematic differences in activation overlap, our findings revealed an increase in spatial heterogeneity of activation patterns in patients with epilepsy relative to healthy controls.

Yu-Sheng Tseng¹, Yao-Wen Chang¹, and Teng-Yi Huang^1
1National Taiwan University of Science and Technology, Taipei, Taiwan

This study attempts exploiting multi-focal functional MRI(fMRI) for retinotopic mapping, or retinotopy, in the primary visual cortex. We tried to reconstruct visual image according the retinotopy and brain activities obtained by fMRI. We empirically found that the accuracy of the reconstructed visual image largely depended on the threshold selection. Therefore, this study proposed an approach to find the optimal threshold according to a receiver operating characteristic analysis. The results obtained with 10 participatns volunteers using the optimized t thresholds demonstrated an average accuracy of 81%.

Cesar Caballero Gaudes^1,2, Fikret Isik Karahanoglu³, François Lazeyras², and Dimitri Van de Ville^2,3
1Basque Center on Cognition, Brain and Language, Donostia-San Sebastian, Guipuzcoa, Spain, ²Department of Radiology and Medical Informatics, University of Geneva, Geneva, Geneva, Switzerland, ³Medical Image Processing Lab, Ecole Polytechnique Federale de Lausanne, Lausanne, Vaud, Switzerland

Paradigm-free mapping (PFM) enables to map the BOLD response in space and time without prior knowledge of the timing of the events using sparsity-promoting estimators, such as the Dantzig Selector or LASSO. Here, we extend PFM by using hierarchical structured sparsity-promoting estimators (Group-LASSO, Weighted-Fusion and Group-Weighted-Fusion) along with an informed basis set in order to deal with BOLD response variability, and use the monotone fast iterative shrinkage thresholding algorithm to solve this deconvolution problem. Experimental results demonstrate that the new approach has superior abilities to characterize single-trial BOLD responses with no prior timing information at 3T.

Anders Eklund¹, Malin Björnsdotter^2,3, Johannes Stelzer⁴, and Stephen LaConte^1,5
1Virginia Tech Carilion Research Institute, Roanoke, Virginia, United States, ²University of Gothenburg, Göteborg, Sweden, ³Nanyang Technological University, Singapore, Singapore, ⁴Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ⁵School of Biomedical Engineering & Sciences, Virginia Tech-Wake Forest University, Blacksburg, Virginia, United States

The searchlight algorithm is a popular choice for locally-multivariate decoding of fMRI data. A substantial drawback of searchlight is the increase in computational complexity, compared to the univariate general linear model. This is especially true for large searchlight spheres, non-linear classifiers, cross validation schemes and statistical permutation testing. Here we therefore present a graphics processing unit (GPU) implementation of the searchlight algorithm, to enable fast locally-multivariate fMRI analysis. The GPU implementation is 21 times faster than a multithreaded Matlab implementation. This makes it possible to apply 10 000 permutations with leave-one-out cross-validation in about 19 minutes.

Robert L. Barry^1,2 and John C. Gore^2,3
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ³Vanderbilt University, Nashville, TN, United States

Phase regression exploits the temporal evolution of phase in individual voxels to suppress BOLD fluctuations from larger vessels while preserving signal changes from microvascular effects. However, the efficacy of this algorithm is hindered when the phase time series exhibits low signal-to-noise ratio. We demonstrate that Savitzky-Golay filters may be used to recover the underlying change in phase and completely restore the efficacy of phase regression. This approach is shown to work on data acquired with single-shot and multi-shot pulse sequences, and should be useful for both human and animal gradient-echo fMRI at high spatial resolutions at high- and ultra-high fields.

Tynan Stevens¹, Steven Beyea², Ryan D'Arcy³, and David Clarke^1
1Dalhousie University, Halifax, Nova Scotia, Canada, ²NRC, Halifax, Nova Scotia, Canada, ³Frasier Health Authority, Surrey, British Columbia, Canada

The Rombouts overlap coefficient (Roverlap) is used extensively in fMRI reliability research. While it is widely recognized that this coefficient depends on analysis threshold, existing studies do not agree on the precise relationship between Roverlap and threshold, and so no clear strategy has been employed across studies. We argue that individual variability in the Roverlap-threshold relationship reduces the information available in group level Roverlap results. This variability likely contributes to the inconsistent findings in the literature to date. We thus suggest that control of reliability is best conducted at the individual-level, as group trends may not be truly representative.

Waqas Majeed¹, Feng Wang^2,3, Robert M. Friedman⁴, Chaohui Tang^2,3, and Malcolm J. Avison^2,3
1Department of Electrical Engineering, Lahore University of Management Sciences, School of Science and Engineering, Lahore, Punjab, Pakistan, ²Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University, Nashville, TN, United States, ³Department of Radiology, Vanderbilt University, Nashville, TN, United States,⁴Department of Psychology, Vanderbilt University, Nashville, TN, United States

Bootstrap stability analysis (BSA) has previously been shown to be a more robust and accurate method for ICA model order estimation, compared with traditional methods. However, large computational burden associated with BSA makes it impractical. In this work, we demonstrate that BSA can be used on the prefiltered and downsampled data without compromising the results, while reducing the processing time to a great degree.

Paul Wighton¹ and André J. W. van der Kouwe^1
1Department of Radiology, MGH, Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States

In most real-time fMRI paradigms, suitable regions of interest (ROIs) must be computed quickly after localization scans have been acquired and before the real-time paradigm can begin. We have developed software that can quickly generate ROIs by leveraging existing software packages. We demonstrate our software by computing ROIs: 1) Using a functional localizer 2) using a structural scan and reference data (either an atlas or a previous scan of the subject) and 3) Using a functional localizer constrained by structural data. We validate our software using a finger-tapping paradigm and flashing checkerboard paradigm.

Victoria L. Morgan^1,2, Megan Strother², and Reid C. Thompson^3
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ³Neurosurgery, Vanderbilt University, Nashville, TN, United States

Due to the high variability in the anatomy and physiology of the patients who undergo functional MRI for clinical presurgical mapping of eloquent cortex, it is difficult to determine metrics for quality evaluation and to compare different analysis strategies. In this work we show that increased motion is reflected in decreased temporal signal to noise (tSNR) in both motor and language tasks. However, when performing motor tasks the focal activation is robust across levels of tSNR, motion and analysis methods; but when performing language tasks, the activation levels and spatial maps can be significantly affected by these factors.

Aaron Benjamin Simon¹, Valerie E M Griffeth¹, and Richard B. Buxton^2
1Bioengineering, University of California San Diego, La Jolla, CA, United States, ²Radiology, University of California San Diego, La Jolla, CA, United States

We examined whether we could estimate the CMRO₂ response to a stimulus, as well as the uncertainty of that estimate, by measuring baseline R₂' and the CBF and BOLD responses. We related the three measurements to the CMRO₂ response through a detailed, multi-compartment BOLD model and adopted a Bayesian approach to determine how uncertainty in unmeasured physiological parameters of the model affected the precision of the estimate the CMRO₂ response. We tested the method with a hypercapnia challenge and found that the estimate agreed well with previous work but that the unmeasured parameters produced considerable uncertainty in the estimate.

Jaakko Paasonen¹, Joanna K. Huttunen¹, and Olli Gröhn^1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland

Anesthesia is one of the most critical factors in designing a phMRI study. We investigated the BOLD signal changes under six different anesthesia protocols with a nicotine challenge in order to find optimal experimental phMRI setup. Nicotine injection in total of 39 rats induced clear cortical signal changes, in all animals, revealing several alternative approaches. However, the choice of anesthetic led to notably different BOLD responses emphasizing the need of optimization of anesthetic conditions for each pharmaceutical agent.

Xiaopeng Zong¹, Mitsuhiro Fukuda¹, Alberto Vazquez¹, and Seong-Gi Kim^1
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States

Dexedetomidine (DEX) is an increasingly popular sedative for fMRI in rodents. To illuminate its effects on neural activity and neurovascular coupling, we carried out electrophysiology, optical imaging, and BOLD fMRI on DEX sedated rats. After continuous DEX infusion for ~2 h, local field potential responses to electrical forelimb stimulation became epileptic with concomitant large increases in cerebral blood flow (CBF). Supplement of ~0.3% isoflurane (ISO) suppressed the generation of the epileptic activity. DEX constricts both arterial and venous vessels at baseline. The DEX+ISO combination yields robust CBF and BOLD fMRI responses, and is a suggested anesthesia for 2-3 h fMRI studies.

Aileen Schröter¹, Felix Schlegel¹, Aline Seuwen¹, Joanes Grandjean¹, and Markus Rudin^1,2
1Institute for Biomedical Engineering, ETH and University Zürich, Zürich, Zürich, Switzerland, ²Institute of Pharmacology and Toxicology, University Zürich, Zürich, Zürich, Switzerland

Functional MR imaging, originally applied in human studies, has been translated back to small animals, which allows performing basic research on animal models of different pathologies. In view of the many transgenic mouse lines the method has been started to be transferred from rats to mice. FMRI in small animals suffers from largely unknown influences of anesthesia, which has been addressed already in studies on rats. However, given species differences, results obtained in rat studies cannot be translated directly to mice. The presented study is characterizing the effects of four anesthetics – isoflurane, urethane, medetomidine, propofol – on fMRI responses in mice.

Diana Cash¹, Tobias C. Wood¹, Camilla Simmons¹, Aisling L. Dixon¹, Steve C.R. Williams¹, and Michel B. Mesquita^1
1Neuroimaging, King's College, Institute of Psychiatry, London, United Kingdom

Forepaw sensory stimulation at 0.5 and 3 Hz in alpha-chloralose-anaesthetized rats was characterized by BOLD-sensitive fMRI. An expected increase in BOLD signal in S1 contralateral cortex was detected at 3Hz, but not at 05Hz where the signal timecourse showed a trend toward decrease. S1 and other areas adjacent to the contralateral S1, as well as the ipsilateral S1 and S2 also showed decreased BOLD signal with both stimulations paradigms. Bilateral subcortical thalamic and striatal BOLD increases were also detected and similar under both stimulation frequencies.

Wen-Ju Pan¹, Matthew E. Magnuson¹, Garth Thompson¹, and Shella Keilholz^1
1Biomedical Engineering, Emory University/ Georgia Institute of Technology, Atlanta, GA, United States

As a first step toward understanding the difference of brain baseline activity in resting state fMRI between awake and isoflurane-anesthetized states in the rat model, we examined the BOLD spectral powers across brain distributions between the two states, and demonstrated the potential usefulness of mapping low frequency BOLD power to assess brain regional activity.

Erik B. Beall¹, John T. Gale², Ken E. Sakaie¹, and Mark J. Lowe^1
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States

Studies of resting connectivity under anesthesia have shown modulation of connectivity patterns with a strong dependence on the choice of anesthetic. Propofol appears to have an increasing usage in human and animal anesthesia connectivity studies. However, it is possible propofol is a poor choice. Based on a failure to find reasonable connectivity patterns in a pilot BOLD scan under propofol, we acquired two long scan sessions (separated by several months) under two different anesthetics and found reasonable connectivity patterns under ketamine but a complete absence of connectivity patterns under propofol.

Johnny Ng¹, Jessica Roman¹, Edmund Wong¹, David Carpenter¹, and Cheuk Tang^1,2
1Dept. of Radiology, Mount Sinai School of Medicine, New York, NY, United States, ²Dept. of Psychiatry, Mount Sinai School of Medicine, New York, NY, United States

Functional imaging in animal models is difficult to perform, especially in awake experiments. Resting-state fMRI is the most convenient way to assess brain function with the animal under anesthesia. The aim of this study is to investigate the effects of three commonly used anesthetic – isoflurane, medetomidine and ketamine – in rodent experiments and their effects on brain function. 14 mice were used in this study. MELODIC ICA and dual-regression analysis were implemented. Increased coactivation has been found in several networks with medetomidine compared with ketamine or isoflurane alone.

Natalia Gass¹, Alexander Sartorius¹, Adam James Schwarz^2,3, Esther Schenker⁴, Celine Risterucci⁵, Michael Spedding⁴, Lei Zheng¹, Andreas Meyer-Lindenberg¹, and Wolfgang Weber-Fahr^1
1Central Institute of Mental Health, Mannheim, Germany, ²Eli Lilly and Company, Indianapolis, Indiana, United States, ³Indiana University, Bloomington, Indiana, United States,⁴Institut de Recherches Servier, Croissy-sur-Seine, France, ⁵F. Hoffmann-La Roche, Basel, Switzerland

The aim of this work was to systematically characterize the effects of ketamine, a rapidly acting antidepressant, on rsfMRI in rat. Male Sprague-Dawley rats in 4 parallel groups received either vehicle or one of three sub-anesthetic doses of S-ketamine. Three rsfMRI datasets were acquired from each rat: pre-injection and 15 and 30 min post-injection. Pharmacokinetic/pharmacodynamic image and region-of-interest analyses revealed increased functional connectivity between the hippocampus and regions in the prefrontal cortex, and within the prefrontal cortex, that positively correlated with ketamine plasma levels. The observed increases in functional connectivity reveal possible neural mechanisms underlying established behavioral effects of ketamine.

Fatima Nasrallah¹, Hui Chien Tay¹, Krzysztof Pyka¹, and Kai-Hsiang Chuang^1
1Magnetic Resonance Imaging Group, A*Star Biomedical Research Institutes, Singapore, Singapore, Singapore

Consistent functional networks have been identified in the resting brain of humans, monkeys, and rats. Since most transgenic models of neurodegenerative diseases are only available in mouse, efforts have been made to detect the resting-state networks in mice. Here we demonstrated, as in other species, robust functional connectivity in the mouse brain and showed, that opposed to what has been shown in the rat, functional connectivity is preserved under high dosages of the commonly used sedative medetomidine.

Bianca Gonzales Cerqueira¹, Glenn M. Toney², and Timothy O. Duong^3
1Research Imaging Institute, Univ. of TX Health Science Center, San Antonio, Texas, United States, ²Physiology, Univ. of TX Health Science Center, San Antonio, Texas, United States, ³Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, Texas, United States

Rat brain BOLD fMRI response to an infusion of alternating isotonic and hypertonic saline was studied. Previous studies have demonstrated that osmosensitive areas of the brain such as the organum vasculosum laminae terminalis can detect small changes in plasma osmolarity and project to the hypothalamic paraventricular nucleus which is involved in sympathetic activation. Increased sympathetic activation is of interest due to its role in many forms of hypertension. There was an significant (p=0.029) increase in average percent change of hypertonic saline (13.79%) compared to isotonic saline (-0.85%) in the anterior medial hypothalamus, which includes osmosensitive areas of the brain. This study demonstrates that non-invasive functional imagining can translated to longitudinal studies of sympathetic activation and hypertension.

Guang Li¹, Jeffrey W. Kiel², Damon P. Cardenas³, De La Garza H. Bryan⁴, and Timothy O. Duong^4
1Department of Radiology, UT Health Science Center at San Antonio, San Antonio, TX, United States, ²Department of Ophthalmology, UT Health Science Center at San Antonio, San Antonio, TX, United States, ³Department of Biomedical Engineering, UT Health Science Center at San Antonio, San Antonio, TX, United States, ⁴Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, TX, United States

While post-occlusion reactive hyperemia has been attributed to metabolic local control (matching of blood flow (BF) to local metabolic demands) in various tissues, post-occlusion reactive hyperemia in the retina has not yet been studied. We found differential BOLD and BF responses in the retinal and choroidal circulations in the retina during and immediately after transient carotid occlusion. Reactive hyperemia was detected in the retina but not in the choroid, suggesting that the retinal circulation is under metabolic local control but the choroid is not. These findings provide novel insights in the hemodynamic regulation of the retinal and the choroidal circulations.

Guang Li¹, Jeffrey W. Kiel², Damon P. Cardenas³, De La Garza H. Bryan⁴, and Timothy O. Duong^4
1Department of Radiology, UT Health Science Center at San Antonio, San Antonio, TX, United States, ²Department of Ophthalmology, UT Health Science Center at San Antonio, San Antonio, TX, United States, ³Department of Biomedical Engineering, UT Health Science Center at San Antonio, San Antonio, TX, United States, ⁴Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, TX, United States

Reactive hyperemia has been attributed to metabolic local control in which BF is trying to match local metabolic demands. In the retina, reactive hyperemia and the effect of occlusion duration on reactive hyperemia have not yet been studied. This study used BOLD and laser speckle BF measurements to investigate reactive hyperemia after graded occlusion durations and probe the reactive hyperemia capacity reserve in the retina. We found that the retinal circulation is under metabolic control but it has smaller capacity for reactive hyperemia compared to other organs (i.e., brain, intestine, heart, etc).

Guang Li¹, Jeffrey W. Kiel², Damon P. Cardenas³, De La Garza H. Bryan⁴, and Timothy O. Duong^4
1Department of Radiology, UT Health Science Center at San Antonio, San Antonio, TX, United States, ²Department of Ophthalmology, UT Health Science Center at San Antonio, San Antonio, TX, United States, ³Department of Biomedical Engineering, UT Health Science Center at San Antonio, San Antonio, TX, United States, ⁴Research Imaging Institute, UT Health Science Center at San Antonio, San Antonio, TX, United States

Reactive hyperemia and its modulation by varying metabolic demands have not been studied in the retina. We investigated the reactive hyperemia and hemodynamic reserve in the rat retina by measuring blood flow and oxygenation under dark, constant light and flicker. Our results showed that changes in metabolic rate by light conditions did not affect the reactive hyperemia likley because of the small BF reserve in the retinal circulation, suggesting that metabolic autoregulation in the retina is less able to compensate for increased metabolism.

Tzu-Hao Chao¹, Jyh-Horng Chen², and Chen-Tung Yen^1
1Institute of Zoology, National Taiwan University, Taipei, Taiwan, ²Interdisciplinary MRI/MRS Lab, Dept. of Electrical Engineering, National Taiwan University, Taipei, Taiwan

The purpose of the present study was to setup a protocol to follow BOLD response by deep brain stimulation longitudinally in the same rat. A pair of tungsten microwire electrode was chronically implanted in the ventroposterior thalamus (VP), and fMRI scan was made under dexmedetomidine anesthesia. We found the electrode caused limited distortion to MR signal in EPI images. VP stimulation-evoked BOLD responses in the primary somatosensory cortex were stable over 2 scan sessions separated by 7 days. Using this protocol, normal and abnormal plasticity change of specific brain pathway can be probed during their development and maintenance stages.

Yu-Chieh Jill Kao¹, Hsin-Yi Lai¹, John Robert Younce¹, and Yen-Yu Ian Shih^1
1Experimental Neuroimaging Laboraory, Department of Neurology and Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, Chapel Hill, NC, United States, Chapel Hill, NC, United States

This is the first study demonstrating the feasibility of deep brain stimulation (DBS) fMRI in mice. Robust CBV response in the somatosensory cortex was observed during DBS at the mouse ventral posteromedial thalamus. Optimal DBS frequency was found at 20 Hz which is similar to that in rats. The proposed mouse DBS fMRI technique provides a new insight into the future investigation of DBS mechanism and assessment of DBS treatment outcome.

Joonas Arttu Autio^1,2, Artem Shatillo¹, Rashid Giniatullin¹, and Olli Gröhn^1
1Neurobiology, University of Eastern Finland, Kuopio, Kuopio, Finland, ²Radiology, University of Oulu, Oulu, Oulu, Finland

Using functional magnetic resonance imaging (fMRI) of the rat brain we found a novel type of parenchymal fMRI signals during large increases in metabolism. Cortical spreading depression (CSD), a self-propagating wave of tissue depolarization, associated with several pathological conditions such as migraine and stroke, was used as paradigm to evoke enhanced brain metabolism. The underlying CSD activated signal changes were investigated using spin-lock (SL), T1 relaxation in the rotating frame (T1ñ), weighted fMRI. Our results show that during CSD propagation SL-fMRI signal is generated by endogenous parenchymal mechanisms.

William M. Spees^1,2, Tsen-Hsuan Lin³, and Sheng-Kwei Song^1,2
1Department of Radiology, Washington University, St. Louis, MO, United States, ²Hope Center for Neurological Disorders, Washington University, St. Louis, MO, United States,³Department of Physics, Washington University, St. Louis, MO, United States

Recently, we have implemented diffusion fMRI and demonstrated its utility for detecting white-matter axonal activation in the optic nerve of healthy mice. A robust (27%) and completely reversible stimulus-induced decrease in the apparent diffusion coefficient perpendicular to the axonal fibers was observed with the application of a flashing-light visual stimulus. The change in ADC parallel to the axonal fibers was not statistically significant. The results of hypercapnia experiments suggest minimal contribution from vascular effects.

Jacques Machol IV¹, Rupeng Li², Patrick Hettinger¹, Nicholas Flugstad¹, Ji-Geng Yan¹, Hani Matloub¹, and James S. Hyde^2
1Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI, United States, ²Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

In the case of severe brachial plexus root avulsion injuries, the contralateral C7 (cC7) nerve root is identified as a possible donor for nerve transfer. It is of interest to the peripheral nerve surgeon as to how the cC7 root can serve as a “spare nerve.” This study uses BOLD fMRI to elucidate the linear relationship in the sensory C7 nerve root cortical map makeup of each major upper limb nerve (ulnar, median, radial, and musculocutaneous) by means of sensory stimulation. This investigation helps to expound why C7 is a suitable donor for brachial plexus injury treatment.

Valerio Zerbi¹, Maarten Van Beek¹, Diane Jansen¹, Christian F. Beckmann^2,3, Amanda J. Kiliaan¹, and Arend Heerschap^4
1Anatomy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Netherlands, ²Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Netherlands, ³MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, Netherlands, Netherlands, ⁴Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Netherlands

Cholesterol released from apoE-containing lipoprotein is used for synaptogenesis and synaptic maintenance. The apoE4 isoform is a less potent cholesterol transporter, which in turn is linked to impaired synaptic connectivity. Resting-state fMRI experiments showed marked differentiation in functional networks compared with non-apoE4 carriers. We tested in apoE4 and apoE-ko mice the hypothesis that dysfunctional apoE, and further its absence, are related to reduced brain functional connectivity. Results indicate that apoE4 and, more severely, apoE-ko mice have lower functional connectivity between several brain areas compared to wild-type, providing new evidences of a dependency between the apoE genotype and the functional connectivity.

Zhixin Li¹, B. Douglas Ward², Melinda R. Dwinell³, and Christopher P. Pawela^1,2
1Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI, United States, ²Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ³Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, United States

The goal of study was to reveal the region-specific effects of genetic differences between two inbred rat strains, Brown Norway (BN) and Dahl salt-sensitive on a biologic measure in brain using BOLD-fMRI under a well-established task paradigm. The Differential BOLD response to electrical stimulation in two inbred rat stains were mainly detected in contralateral S1FL, S2, TH, and bilateral CPu regions. These results suggest a new approach to visualize the genetic effects on the brain using neuroimaging measures.

Prantik Kundu^1,2, Mathieu David Santin³, Alexandra Petiet³, Peter A. Bandettini⁴, Ed Bullmore², and Stéphane Lehéricy^3
1Section on Functional Imaging Mehthods, NIMH, Bethesda, MD, United States, ²Dept. of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom,³UPMC/INSERM UMR_975 CNRS 7225, CENIR,ICM,CRICM, Paris, France, ⁴Section on Functional Imaging Mehthods, National Institute of Mental Health, Bethesda, MD, United States

Rat resting state fMRI (rs-fMRI) is an exciting platform for functional and pharmacological neuroscience, but its capabilities and limits are not yet well understood. Distinguishing neuronally-related BOLD signals from non-BOLD artifact in rat rs-fMRI is an important methodological step. Here we distinguish BOLD and non-BOLD signals in rat rs-fMRI using multi-echo ICA. We show multi-echo ICA of 11.7T rat fMRI data produces consistent components showing clear localization of functionally and neuropharmacologically interesting brain areas.

Ikuhiro Kida¹, Yoko Hoshi², Masahito Nemoto², Yoshinobu Iguchi², and Yoshichika Yoshioka^3
1Center for Information and Neural Networks, National Institute of Information and Communications Technology, Suita, Osaka, Japan, ²Integrated Neuroscience Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan, ³Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan

Our previous study using BOLD fMRI demonstrated that tastants evoke bilateral responses in the insular cortices, but that these representations are asymmetrical in rodents. There are two possible interpretations of asymmetrical responses: asymmetrical functional representations or asymmetrical positions of the insular cortices. We performed MRA and optical imaging to measure the anatomical positions and functional representations, respectively, of the insular cortices. We found that the bilateral gustatory cortices have symmetrical functional representations, but contain anatomical asymmetries that result in bilateral asymmetry. This suggests that the cerebral vasculature provides a reliable reference point for functional representations in the gustatory cortex.

Roger J. Mullins^1,2, Da Shi^1,3, Jiachen Zhuo¹, Su Xu¹, and Rao P. Gullapalli^1
1Diagnostic Radiology and Nuclear Medicine, Core for Translational Research in Imaging @ University of Maryland, Baltimore, Maryland, United States, ²Program in Neuroscience, University of Maryland, Baltimore, Maryland, United States, ³Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, Maryland, United States

It is well known that fixation in paraformaldehyde (PFA) alters MR characteristics, but the extent that sucrose infiltration may affect the MR signal and image quality has not been examined. Scanning ex vivo mouse brains revealed lowered mean, axial and radial diffusivity in brains immersed in 30% sucrose compared to brains in 4% PFA. However, higher T2 relaxation and signal intensity was found in samples immersed in 30% sucrose. Brains immersed in 4% PFA were more similar to in vivo DTI, in terms of T2 relaxation and signal intensity.

Philipp Lebhardt^1,2, Wolfgang Kelsch³, Apar Jain⁴, Miriam Kernert⁴, Valery Grinevich⁴, Gabriele Ende⁵, Andreas Meyer-Lindenberg², Alexander Sartorius^1,2, and Wolfgang Weber-Fahr^1,5
1RG Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany, ²Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany, ³RG Developmental Biology, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany, ⁴Laboratory of Neuropeptides, German Cancer Research Center DKFZ, CellNetwort Cluster of Excellence, University of Heidelberg, Heidelberg, Germany, ⁵NeuroImaging, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany

We are presenting preliminary results on a study investigating the BOLD response of the oxytocinergic network in the rat brain stimulated via optogenetics. We selectively expressed Channelrhodopsin-2-mCherry in oxytocin neurons. The guide cannula was implanted into the central amygdala for subsequent stimulation with an implanted optic fiber. Rats were subjected to a fear conditioning protocol and displayed substantial reduced fear response after blue light-evoked axonal oxytocin release within the central amygdala. Using a blocked laser activation fMRI scanning protocol we could show projections from the central amygdala to the superior colliculus in both rats investigated.

Neele Saskia Hübner^1,2, Anna Mechling¹, Hsu-Lei Lee¹, Jürgen Hennig¹, Dominik von Elverfeldt¹, and Laura-Adela Harsan^1
1Department of Radiology - Medical Physics, University Medical Center Freiburg, Freiburg, Germany, ²Faculty of Biology, University of Freiburg, Freiburg, Germany

This study demonstrates the potential of resting state functional magnetic resonance imaging for investigating the mouse brain functional networks in normal and pathological conditions. We investigate the impact of experimentally induced demyelination on the functional connectivity of cuprizone demyelinated mice. Data derived from independent component analysis combined with partial correlation analysis and graph theory indicate a complex remodeling of the large scale functional networks in the mouse brain as an effect of demyelinating pathology.

Shiliang Huang¹, Fang Du², Yen-Yu Ian Shih^2,3, Qiang Shen², Francisco Gonzalez-Lima⁴, and Timothy O. Duong^2
1University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²UT Health Science Center at San Antonio, San Antonio, TX, United States,³University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ⁴The University of Texas at Austin, Austin, TX, United States

Methylene blue (MB) at low doses has metabolic-enhancing and antioxidant properties and exhibits experimental neurotherapeutic benefits, but little is known about its in vivo effects on cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2). We previously reported that MB (0.5 mg/kg) potentiated evoked BOLD, CBF and CMRO2 changes in rat brain under normoxia. This study further evaluated the effects of MB under stress condition (mild hypoxia: 15% O2). We found that MB further potentiated fMRI responses under mild hypoxia relative to air. These findings have implications in neurological conditions with mitochondrial dysfunction and oxidative stress.

Nellie E. Byun^1,2, Robert L. Barry^2,3, Michael D. Grannan⁴, Stephen M. Damon⁵, Nathaniel D. Kelm^2,6, Matthew J. Mulder¹, Amanda W. Huang¹, Thomas M. Bridges^1,4, Malcolm J. Avison^2,3, Craig W. Lindsley^1,7, Jeff Conn^1,4, John C. Gore^2,3, and Carrie K. Jones^1,4
1Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, United States, ²Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States,³Radiology & Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ⁴Pharmacology, Vanderbilt University, Nashville, TN, United States, ⁵Neurology, Vanderbilt University, Nashville, TN, United States, ⁶Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, ⁷Chemistry, Vanderbilt University, Nashville, TN, United States

Pharmacological MRI was used to determine the effects of a selective M4 muscarinic acetylcholine receptor positive allosteric modulator, VU0152100, on amphetamine-evoked dopaminergic neurotransmission and functional connectivity in rats in vivo. VU0152100 blunted amphetamine-evoked activation in striatal regions, consistent with separate microdialysis results, as well as in thalamus and hippocampus. Functional connectivity analysis revealed multiple functional correlations in the amphetamine group and loss of correlations with VU0152100 pretreatment, notably for retrosplenial and accumbal connections. These findings support potentiation of endogenous cholinergic activity at M4 as a novel antipsychotic mechanism through which dopaminergic activity can be modulated without directly targeting dopamine receptors.

Cecil Chern-Chyi Yen¹, Daniel Papoti¹, and Afonso C. Silva^1
1CMU/LFMI/NINDS, National Institutes of Health, Bethesda, MD, United States

To better interpret the result from the BOLD fMRI, a comprehensive understanding of the spatiotemporal characteristic of the BOLD response is critical. In the present study, we have demonstrated the use of the novel RF coil design and refined data processing scheme to study BOLD response in the awake marmoset, a small non-human primate. Robust BOLD responses were detected in the primary and secondary somatosensory areas, as well as in the caudate nucleus. Without the confounds of anaesthesia and concerns of phylogenetic disparity, this novel animal model may shed light on the characteristic of the neural activity evoked hemodynamic response.

Lindsay S. Cahill¹, Yu-Qing Zhou¹, Mike Seed², Christopher K. Macgowan^2,3, and John G. Sled^1,3
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada, ²Hospital for Sick Children, Toronto, Ontario, Canada, ³Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Fetal growth restriction is often associated with brain sparing whereby a greater proportion of oxygenated fetal blood is directed to the brain at the expense of other organs. Understanding the physiology of this response may lead to better diagnostic procedures for predicting fetal risk. Here, BOLD MRI contrast is used to characterize the redistribution of fetal blood flow that occurs in mice under hypoxic conditions. As the maternal inspired gas mixture is varied, large BOLD signal changes were observed in the fetal liver but not in the brain. Using Doppler ultrasound, cerebral blood flow was observed to rise under hypoxia.

Lei Zhang¹, Min LI¹, and Zhen Jin^1
1Medical Imaging Center, 306 Hospital Beijing, Beijing, Beijing, China

Benito de Celis Alonso¹, Silvia Hidalgo Tobón², Pilar Dies Suarez², Samuel Flores Huerta², Jenny Vilichis², Manuel Obregon Espejel², Porfirio Ibañez Fernández², and Eduardo Castro Sierra^2
1Faculty of Medicine, BUAP, Puebla, Puebla, Mexico, ²Hospital Infantil de México, Mexico City, México FD, Mexico

Obesity is a precursor of health problems (i.e. in cardiology, neurology, endocrinology, etc.). In Mexico this condition affects more than 70% of the population with a special prevalence in the infant bracket. It is known that odor/smell is one of the principal cues for the appearance and control of appetite. To fight obesity it is crucial to understand the brain mechanisms of this stimulus. Previous fMRI work has shown that adult obese and lean subjects interpret these types of stimuli differently. Nevertheless and surprisingly, no studies have been performed in infants and adolescents who have different metabolism and brain development from adults. Furthermore, there is no information on the changes in connectivity between brain regions for this age group. In this work we studied the different brain fMRI activations and connections between normal weighted and obese adolescents for different types of food odors.

Stephen D. Mayhew¹ and Andrew P. Bagshaw^1
1BUIC, School of Psychology, University of Birmingham, Birmingham, United Kingdom

We use model-free analysis to characterise the spatio-temporal dynamics activity in multiple brain networks both preceding and during visual and pain stimulation paradigms. We find that stimulus modulations occur at multiple time-points, creating high degree of variability in the shape and polarity of trial-by-trial brain responses. The pre-stimulus BOLD signal amplitude in the DAN and DMN was found to predict the amplitude of the primary visual and pain stimulus-responses. Studying the temporal evolution of responses both in brain regions directly driven by stimulation as well as more subtly recruited networks provides greater insight into the complexity of brain processing.

Mitsunobu Kunimi¹, Sachiko Kiyama¹, and Toshiharu Nakai^1
1National Center for Geriatrics and Gerontology, Obu, Aichi, Japan

We attempted to evaluate the validity of divalent Task Switching Paradigm (TSP) as a cognitive stress test. Fifteen young and 15 elderly volunteers participated. The brain areas with augmented brain activation depending on the difficulty of TSP task were different between the two age groups. In particular, it was observed that the contrast of Elderly against Young of right caudate nucleus and hit rate score was significantly correlated with the activation in the right caudate nucleus in the Elderly. Evaluation of the activation in the caudate nucleus using TSP may be valid to represent the aging effects on reconfiguration function.

Zhi Yang^1,2, Javier Gonzalez-Castillo², Zirui Huang¹, Rui Dai¹, Georg Northoff³, and Peter A. Bandettini^2
1Institute of Psychology, Chinese Academy of Sciences, Beijing, China, ²National Institute of Mental Health, Bethesda, MD, United States, ³University of Otawa, Otawa, ON, Canada

Multivariate pattern analyses were used to decode the subjectively correct "Yes/No" answers to binary questions. Using a spatiotemporal searchlight approach, a set of brain regions were identified in 10 subjects in a 3T scanner, showing group-level above-chance accuracy in decoding "Yes/No" answers regardless the subjects' intentions that were manipulated in the experimental paradigm. The results from 7T scans further verified that three of these regions can be used to robustly decode the “Yes/No” answers (regardless of intentions) with high accuracy, given sufficiently high TSNR, which can be achieved by means of ultra-high field scanners and trial-averaging. These findings suggest that subjectively correct answers can be accurately decoded with fMRI in the spatial-temporal patterns of prefrontal cortex, providing a basis for fMRI-based brain-computer interface.

Bob Hou¹, A Smith², J. Wiener², J. Chong², Julie Brefczynski-Lewis¹, D Kerr², D. G. McLaren³, and Marc W. Haut^2
1Radiology, WVU, Morgantown, WV, United States, ²Behavioral Medicine & Psychiatry, WVU, Morgantown, WV, United States, ³MGH, Harvard University, Cambridge, MA, United States

Attention training (AT) results in changes in brain structure, grey matter and the connections of the structures (i.e., brain plasticity). Here we present our study on applying resting state functional MRI (rfMRI), DTI, and high resolution structural images to examine the impact of AT on brain plasticity of healthy highly educated subjects. Our hypothesis was that brain plasticity including functional and structural connectivity and grey matter volumes results from AT within 2 weeks. Our results of rfMRI, DTI, and tensor based morphometry (TBM) on the AT of the healthy highly educated subjects demonstrated the brain plasticity indeed happened within 2 weeks.

Jeehye Seo¹, Seong-Uk Jin¹, Hee-Kyung Kim¹, Jang Woo Park¹, Moon Han¹, Jong Su Baeck¹, Yongmin Chang^1,2, and Kyung Jin Suh^3
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, ²Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea, ³Radiology, College of Medicine, Dongguk University, Gyeong Ju, Gyeongsangbuk-do, Korea

A decline in working memory is well documented with increasing age and age-related differences are seen in working memory tasks using functional neuroimaging techniques . The aim of this study is to elucidate age-related effects on functional activation during working memory task through continuous distribution of age. Sixty-eight healthy subjects aged 18 to 70 years old performed an n-back memory task. We found that with increasing age, working memory activation network showed decreased activation, whereas 2-back deactivation network showed increased brain activation. Decreased brain activity has interpreted as a reflection of cognitive deficits in older adults, and increased activity has interpreted as compensatory.

Sachiko Kiyama¹, Mitsunobu Kunimi¹, Tetsuya Iidaka², and Toshiharu Nakai^1
1National Center for Geriatrics and Gerontology, Ohbu, Aichi, Japan, ²Nagoya University, Nagoya, Aichi, Japan

This study examined the applicability of a cognitive performance task for the elderly, focusing on visuomotor coordination of bimanual finger movements. In order to detect difference of the elderly�fs neural activity, an fMRI study was conducted during bimanual finger-tapping task on elderly and younger adults. Group analyses revealed that movement frequency of this task influenced on activation in left cuneus and bilateral IFG, whereas the tapping mode (i.e., symmetrical/asymmetrical) did not differentiate their activity. This result suggests that movement velocity of visuomotor finger-tapping task, rather than its mode difference, may work as a detector of difference in the elderly�fs cognitive performance.

Claudia Huerta¹, Pooja Sarkar¹, and Timothy O. Duong^2
1UTHSCSA, San Antonio, TX, United States, ²UT Health Science Center at San Antonio, San Antonio, TX, United States

Obesity is at an epidemic proportion. This study used fMRI to probe the neural responses to visual food cues in lean and obese subjects in “fasted” and “satiated” state. We identified stronger activities in structures, such as orbitofrontal cortex and fusiform gyrus, known to engage in reward processing and attention in obese compared with lean. We also found that the orbitofrontal cortex activation did not decrease after eating in obese compared to lean subjects. Our results suggest there are strong neural correlates in eating disorders, which may involve the reward/craving circuitry.

Claudia Huerta¹, John Li¹, and Timothy O. Duong^2
1UTHSCSA, San Antonio, TX, United States, ²UT Health Science Center at San Antonio, San Antonio, TX, United States

This study used fMRI to investigate the neural networks responding to ingestion of a standardized glucose solution by correlation with blood glucose levels. In addition to identified hypothalamic activation, we detected a large neural network that regulates satiety. Future studies will examine subjects with eating disorders and correlate with temporal profiles of other blood markers (such as c-peptide) and behavioral data of satiety.

Tetsuya Iidaka¹, Makoto Miyakoshi², Tokiko Harada³, and Toshiharu Nakai^4
1Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan, ²Swartz Center for Computational Neuroscience, Institute for Neural Computation, UC San Diego, La Jolla, CA, United States, ³NIPS, Okazaki, Aichi, Japan, ⁴Neuroimaging & Informatics, NCGG, Ohbu, Aichi, Japan

We performed fMRI in combination with DTI in 30 healthy young subjects. Face-specific brain activation in the superior temporal sulcus (STS) and amygdala (AMG) was identified. Probabilistic tractography indicated a white matter pathway between the face-specific regions of interest in the STS and AMG. The volume of connectivity between the STS and AMG correlated positively with the total AQ score (p<0.05); however, among the AQ subscales, only imagination was significantly associated with the connectivity volume. Healthy subjects with high autistic traits may show an increase in the white matter pathway that connects key regions involved in face processing.

Chuzo Tanaka¹, SETSUO Hakata², Tomokazu Murase³, Masahiro Umeda⁴, Yasuharu Watanabe⁴, Yuko Kawai⁵, Yoshiaki Someya⁶, Shoji Naruse⁷, and Toshihiro Higuchi^8
1Meiji University of Integrative Medicine, Kyoto, Kyoto, Japan, ²Japanese Medical Society of Arthrokinematic Approa, Fujiyoshida, Yamanashi, Japan, ³Dept. of Neurosurgery, Meiji University of Integrative Medicine, Nantan-shi, kyoto, Japan, ⁴Dept. of Medical Informatics, Meiji University of Integrative Medicine, Nantan, Kyoto, Japan, ⁵Dept. of Medical Informatics, Dept. of Medical Informatics, Nantan, Kyoto, Japan, ⁶MR center of COE, Keio University, Yokohama, Kanagawa, Japan, ⁷2nd Okamoto General Hospital, Kyoto, Kyoto, Japan, ⁸Dept. of Neurosurgery, Meiji University of Integrative Medicine, Nantan, Kyoto, Japan

We studied to clarify the effect of passive intra-articular movement to the brain using fMRI. Stimulation of joint movement consisted of three kinds of stimulations – passive joint movement of wrist for control, passive intra-articular movement of radiolunate joint, and sacroiliac joint. Main activated areas of radiolunate joint were ipsilateral cerebellum, contaralateral insular cortex and motor cortex. Main activated areas by sacroiliac joint were contaralateral insular cortex and ipsilateral BA 7. Relief of joint pain may be modified by these brain areas to manipulate intra-articular movement. This is a first basic study of manual therapy using fMRI.

Robert Trampel¹, Andreas Schäfer¹, Laurentius Huber¹, Robin Martin Heidemann², Gabriele Lohmann¹, and Robert Turner^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Siemens AG Healthcare Sector, Erlangen, Germany

The functional properties of the somatosensory system have been intensively studied by functional MRI over the last decades. Somatosensory cortex clearly discriminates touch of self and other objects: one cannot tickle oneself. Using unsmoothed isotropic sub-millimeter fMRI at 7 Tesla, and a paradigm comprising finger tapping and finger movement without fingertip touching, we found an area of robust deactivation in contralateral Brodmann area 3b, consistent with active suppression of somatosensory activity during the anticipation and experience of self-generated touch.

Yue Zhang¹, Christopher B. Glielmi², Yin Jiang³, Jing Wang¹, Xiaoying Wang⁴, Jing Fang¹, Cailian Cui³, Jisheng Han³, Xiaoping P. Hu², and Jue Zhang^1
1College of Engineering, Peking University, BeiJing, BeiJing, China, ²Department of Biomedical Engineering, Georgia Institute of Technology / Emory University, Atlanta, GA, United States, ³Neuroscience Research Institute, Peking University, Beijing, Beijing, China, ⁴Department of Radiology, Peking University First Hospital, Beijing, Beijing, China

This study mapped brain activity elicited by high frequency electroacupuncture by simultaneously using blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) contrasts. Forty subjects participated in the study, in which twenty ones were imaged during electrical acupoint stimulation (EAS) to the left LI4 acupoint at a maximal intensity without pain, and the others with a minimal-EAS at a just detectible intensity. Both BOLD and CBF data were acquired simultaneously during alternating blocks of rest and stimulation. The results revealed concordant and complementary insights into the neural effects of EAS, including modulation of subcortical structures and limbic system.

Jozien Goense¹, Yvette Bohraus¹, and Nikos K. Logothetis^1,2
1Dept. Physiology of Cognitive Processes, Max-Planck Institute for Biological Cybernetics, Tuebingen, Germany, ²Division of Imaging Science and Biomedical Engineering, University of Manchester, Manchester, United Kingdom

In earlier work, we showed increased CBV in regions with negative BOLD responses. This seems to disagree with work in cats where CBV was decreased in areas with negative BOLD. Here, we used a full-field checkerboard stimulus and show decreased CBV and CBF in areas that show negative BOLD responses. However, this type of negative BOLD signals occurred in peripheral V1 and extrastriate visual cortex. Our results suggest that different mechanisms for negative BOLD exist and that these may be area-dependent.

Stephen D. Mayhew¹, Karen J. Mullinger², Camillo Porcaro^3,4, Richard W. Bowtell², Andrew P. Bagshaw¹, and Susan T. Francis^2
1BUIC, School of Psychology, University of Birmingham, Birmingham, United Kingdom, ²SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, ³Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom, ⁴LETs-ISTC-CNR, Fatebenefratelli Hospital-Isola Tiberina, Rome, Italy

Conventional GLM analyses of fMRI data localise brain activity from the average stimulus response, ignoring trial-by-trial variability which is most relevant to the dynamics of brain function and behavioural outcomes. We combine data from visual, motor and somatosensory tasks to show that single-trial responses across the whole brain are concurrently modulated with activity in the stimulated primary sensory cortex. These modulations induce a positive correlation between single-trial positive and negative BOLD responses, despite a negative correlation between the average response magnitudes. These findings demonstrate that stimulus modulations extend over a far greater extent of the brain than previously suspected.

Tomokazu Murase¹, Masahiro Umeda², Yuko Kawai², Yasuharu Watanabe², Shoji Naruse³, Chuzo Tanaka¹, and Toshihiro Highchi^1
1Department of Neruosurgery, Meiji University of Integrative Medicine., Nantan, Kyoto, Japan, ²Department of Medical Informatics, Meiji University of Integrative Medicine., Nantan, Kyoto, Japan, ³Daini Okamoto General Hospital, Uji, Kyoto, Japan

We focused on the temporal changes in brain activity caused by acupuncture stimulation with deconvolution analysis to analyze brain responses without the expected reference function. For statistical analysis, 3dDeconvolve, which is part of the AFNI package, was used to extract the impulse response functions (IRFs) of the fMRI signals on a voxel-wise basis. Delayed and long-sustained increases of the signal induced by the real acupuncture were observed after stimulation. Especially, in real acupuncture, significantly delayed and long-sustained increases of BOLD signals were observed in several brain regions related to pain perception than those observed in sham acupuncture and palm scrubbing.

Bader Aldebasi¹, Xia Lin², Paul M. Glover¹, Richard W. Bowtell¹, Cris Constantinescu³, and Susan T. Francis^1
1SPMMRC, School of Physics & Astronomy, Nottingham, Nottinghamshire, United Kingdom, ²Division of Rehabilitation and ageing, Nottingham, Nottinghamshire, United Kingdom,³Division of clinical Neurology, Nottingham, Nottinghamshire, United Kingdom

Functional electrical stimulation (FES) is a technique used to elicit ankle dorsiflexion (ADF) movement by electrically stimulating the common peroneal nerve, and used in gait rehabilitation to correct foot drop. Brain activation patterns associated with Active, Passive, Electrical Stimulated (ES) and combined ES plus Active induced ADF of the affected and non-affected leg are compared in ten MS patients. For Active ADF, a significant increase is seen in secondary motor areas for the affected compared to non-affected leg, whilst for ES ADF, significantly reduced activity in the insula and SII is found for the affected leg.

Jeehye Seo¹, Seong-Uk Jin¹, Hee-Kyung Kim¹, Jang Woo Park¹, Moon Han¹, Jong Su Baeck¹, Yongmin Chang^1,2, and Young-Hwan Lee^3
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, ²Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea, ³Radiology, Daegu Catholic University Medical Center, Daegu, Korea

Occupational lead exposure in adults are associated with decreases in cognitive performance including working memory. The aim of this study is to elucidate the differences in neural activation related to working memory between lead exposure subjects and healthy subjects. Thirty-one lead exposure subjects and 34 healthy subjects performed an n-back memory task. We found that healthy subjects showed better performance in terms of accuracy and reaction times during the task. In between-group analyses, lead exposure subjects showed reduced activation in the dorsolateral, dorsomedial and ventrolateral prefrontal cortex, and inferior parietal cortex. Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in lead exposure subjects.

Meghan Robinson^1,2, Evan Breedlove³, Victoria N. Poole^2,4, Larry Leverenz⁵, Eric Nauman^3,4, and Thomas Talavage^2,6
1Translational Research Center for TBI and Stress Disorders (TRACTS), VA Boston Healthcare System, Boston, MA, United States, ²Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States, ³Mechanical Engineering, Purdue University, West Lafayette, IN, United States, ⁴Basic Medical Sciences, Purdue University, West Lafayette, IN, United States, ⁵Health and Kinesiology, Purdue University, West Lafayette, IN, United States, ⁶Electrical Engineering, Purdue University, West Lafayette, IN, United States

We investigated the effects of subconcussive head trauma in a cohort of asymptomatic high school football players. Head impacts were measured via accelerometers in player’s helmets. Changes from pre-season to in-season in fMRI activations during two working memory tasks were measured. These changes were compared to the hit history (number and location of the hits) of the players through a stepwise regression. We found that hits were likely to produce negative correlations in proximal regions and positive correlations in distal regions. This result was consistent across two task types (visual and verbal) and two contrasts.

Nicholas P. Blockley¹, Valerie E M Griffeth², Peter Jezzard¹, and Daniel P. Bulte^1
1FMRIB, University of Oxford, Oxford, United Kingdom, ²Center for Functional MRI, University of California San Diego, La Jolla, California, United States

The calibrated BOLD technique was originally optimised for 1.5T, and was later revised for 3T. However, with the arrival of 7T systems it is unclear what the optimal implementation should be and how this will affect accuracy. In this study we extended an existing detailed model of the BOLD signal to simulate the BOLD response at these field strengths. This model was used to examine the error in oxygen metabolism measurements across fields and provide a guide to the expected BOLD scaling factor M at 7T.

Kang Wang¹, Zachary M. Smith¹, and David J. Dubowitz^1
1University of California San Diego, La Jolla, CA, United States

Hypoxic hypoxia is accompanied by an increase in cerebral O2 metabolism, and despite increased cerebral blood flow there is reduced cerebral tissue oxygentation. We investigated if Acetazolamide (a carbonic anhydrase inhibitor that increases CO2 in the cerebral tissues) improves tissue oxygentaion during hypoxia. CMRO2 was measured using ASL and TRUST at 3T in human volunteers during normoxia, and following 6-hrs hypoxia with or without acetazolamide treatment. Following acetazolamide, the hypoxia-induced rise in CMRO2 and CBF were reduced. This resulted in improved oxygentation in cerebral tissues despite the continued hypoxia.

Kevin Murphy¹ and Molly G. Bright^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom

Cerebrovascular reactivity, the vascular response to vasodilatory stimuli, can be measured with BOLD fMRI by increasing end-tidal CO₂ using a breath-hold task. A long end-expiration breath-hold lasting 20s provides a suitably large BOLD response. However, clinical and elderly populations may find such a long breath-hold difficult and it is likely that the length of breath-hold that each participant can achieve will vary widely across these groups. This study demonstrates that by measuring end-tidal CO₂ changes during a breath-hold task, a repeatable measure of cerebrovascular reactivity can be obtained irrespective of whether the participant can perform the task fully or consistently.

Kenneth A. Weber II^1,2, Yufen Chen¹, Xue Wang¹, and Todd B. Parrish^1
1Department of Radiology, Northwestern University, Chicago, IL, United States, ²Interdepartmental Neuroscience Program, Northwestern University, Chicago, IL, United States

Spinal cord fMRI has lagged behind brain fMRI due to technical difficulties including magnetic susceptibilities at bone-tissue interfaces, the small dimensions of the spinal cord, and physiological noise. Gradient echo EPI (GE EPI) based BOLD fMRI is sensitive to differences in magnetic field susceptibilities at bone-tissue interfaces, which results in signal loss and image distortion. This study investigates steady state free precession, proton density spin-echo EPI, and short TE half-Fourier single-shot turbo spin-echo sequences for functional neuroimaging in the motor cortex to determine their potential for spinal cord fMRI. These data were compared to conventional GE EPI based BOLD fMRI.