Jeroen Cornelis Willem Siero^1,2, Nick F Ramsey¹, Johannes Marinus Hoogduin^1,2, Peter R Luijten², and Natalia Petridou^1,2
1Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, Netherlands, ²Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Understanding the neurovascular coupling mechanism underlying the BOLD fMRI signal is contingent on the accurate spatial and temporal characterization of the hemodynamic impulse response (HIR), linked to the microvasculature. We obtained the spin-echo (SE) HIR at 7T using very short visual stimuli and high temporal resolution, and compared it to gradient-echo (GE) HIR obtained near the pial surface and deeper gray matter (dGM). SE HIR delay matched that of GE HIR in dGM, but the width was much narrower. The SE HIR can lead to new insights to the factors that contribute to the GE HIR.

Xiaopeng Zong¹, and Jie Huang^1,2
1Department of Radiology, Michigan State University, East Lansing, MI, United States, ²Neuroscience Program, Michigan State University, East Lansing, MI, United States

Event-related (ER) BOLD-fMRI offers a means for quantitatively investigating the relationship between the elicited BOLD response and the corresponding brief neural events. The dynamic ER-BOLD response increases for a few seconds and then decreases to baseline, followed by a negative undershoot before returning to the baseline. Using an ER paradigm with voxelwise analysis, this study found that the dynamic BOLD response was highly homogeneous across V1, V2 and V3 and the negative undershoot was correlated with the positive BOLD response in each visual area, suggesting a common impulse hemodynamic response across the visual areas.

Evgeniya Kirilina¹, Ruediger Bruehl², Bernd Ittermann², and Arthur Jacobs^1
1Free University of Berlin, Berlin, Germany, ²Physikalisch-Technische Bundesanstalt, Berlin, Germany

An increasing number of fMRI studies are complemented by measurements of task-evoked changes of the heart rate, the pupil size or the skin conductance. These parameters reflect changes in the autonomic nervous system and may be employed as indicators of emotional and cognitive processes and regressors for fMRI analysis. Here we show that task-evoked changes in sympathetic outflow can be detected exploiting physiological information, which is already contained in the fMRI scan. We demonstrate that by analyzing signal changes induced by stimulus evoked venous constriction in the scalp, information about bodily arousal can be extracted.

Moritz Bernhard Mie¹, and Lothar Rudi Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Knowledge about tissue oxygen supply provides important information about the viability of the tissue. In this study a modification of a model of static dephasing magnetization has been used to measure the oxygen extraction fraction (OEF). The advantage of this technique is the robustness of the values of the reversible relaxation rate R2’, the irreversible relaxation rate R2 and the deoxygenated blood volume DBV, because all parameters were determined in separate measurements.

Erik B Beall¹, Lael Stone², Robert J Fox², Michael D Phillips¹, and Mark J Lowe^1
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Neurologic Institute, Cleveland Clinic, Cleveland, OH, United States

Various preprocessing steps have been shown to affect results of fMRI group analyses, however physiologic noise correction is commonly assumed to have little or no effect due to the orthogonality between pulse/respiration and experimental paradigm. Certain populations have systematically different pulse/respiration rates than the general population, and it is possible that this will affect noise variance, thereby affecting activation statistics. We show in a group analysis of Multiple Sclerosis patients that this is indeed the case, and that group analyses comparing populations with subtly different rates must take physiologic noise into account to avoid biased results.

Xiaoqi Wang¹, Alexander L Sukstanskii², and Dmitriy A Yablonskiy^1,2
1Department of Physics, Washington University, St. Louis, Missouri, United States, ²Department of Radiology, Washington University, St. Louis, Missouri, United States

qBOLD (quantitative Blood Oxygenation Level Depend) technique provides an MRI-based method to measure tissue hemodynamic parameters such as oxygen extraction fraction (OEF) and deoxyhemoglobin-containing cerebral blood volume fraction (dCBV). It is based on a theory of MR signal dephasing in the presence of blood vessel network and experimental method – Gradient Echo Sampling of Spin Echo (GESSE). Herein, using Bayesian approach we present a comprehensive analysis of uncertainties in OEF and dCBV estimates and their dependence on GESSE sequence parameters, thus allowing optimization of qBOLD technique for optimum dCBV and OEF evaluation. Theoretical results are validated in phantom studies.

Sridhar Kannurpatti¹, Bart Rypma², and Bharat Biswal^1
1Radiology, UMDNJ-New Jersey Medical School, Newark, New Jersey, United States, ²School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas, United States

We test the hypothesis that functional Magnetic Resonance Imaging (fMRI) blood oxygenation (BOLD) activity generated during the resting state (R-fMRI) and task-induced states (T-fMRI)originate from a common system. In other words, the activity is equivalent and independent of whether the subject performs a task or remains at rest in the MRI scanner. Using healthy human subjects for the study, we obtained linear relationships between resting signal and task-induced signal amplitudes (defined as the R-T relationship) on a voxel-wise basis and across subjects. Such a result reflects the resting- and task-induced BOLD-fMRI responses to arise from a common system.

Tae Kim¹, and Soeng-Gi Kim^1
1Neuroimaging Laboratory, Radiology, University of Pittsburgh, Pittsburgh, PA, United States

cerebral arterial blood R₂^* and volume, and their changes during stimulation was measured by arterial spin labeling technique with a short labeling duration of 700 ms. R₂^* of arterial blood (53.5 15.3 s^-1) is larger than tissue R₂^* (37.1  7.1 s^-1) at 9.4 T, and the R₂^* change in arterial blood is not significant during stimulation. Arterial blood volume increased from 0.64  0.23 ml/100g to 0.93  0.23 ml/100g during stimulation.

Yoshiyuki Hirano¹, and Afonso C Silva^1
1Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

Biophysical models of BOLD contrast assume that the arterial vasculature is fully saturated with oxygen, so that BOLD originates in capillaries and veins. Here, we measured the BOLD and CBF fMRI response to somatosensory stimulation in -chloralose anesthetized rats under different levels of arterial oxygenation. The CBF response was not affected by arterial oxygenation, while the onset time of the BOLD response in hypoxia was significantly longer than those in normoxia or hyperoxia. The onset time difference between BOLD-CBF was significantly smaller than the arteriole-venule transit time, suggesting that a measurable fraction of the BOLD response is of arterial origin.

Renata Ferranti Leoni^1,2, Draulio Barros de Araujo², and Afonso Costa Silva^1
1Cerebral Microcirculation Unit, National Institute of Neurological Disorders and Stroke - NIH, Bethesda, Maryland, United States, ²Department of Physics and Mathematics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

Compared to other arterial spin labeling (ASL) methods, the dynamic ASL (DASL) technique is an efficient way to obtain information about cerebral hemodynamics. The improved temporal resolution of DASL allows its use in functional MRI experiments. Here we used DASL in combination with somatosensory stimulation in rats, to show that resting cerebral blood flow (CBF), perfusion territories of the major cerebral arteries, transit-times, and both BOLD and CBF responses to functional brain stimulation can be measured simultaneously in a single experiment. This capability makes DASL an efficient and comprehensive technique to investigate the cerebral hemodynamics in scientific and clinical studies.

Barbara Basile¹, Andrea Bassi², Giovanni Calcagnini³, Pietro Cortelli⁴, Carlo Caltagirone^2,5, and Marco Bozzali^1
1Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy, ²Department of Clinical and Behavioural Neurology, Santa Lucia Foundation, Rome, Italy, ³Department of Technology and Health, Italian Institute of Health, Rome, Italy, ⁴Department of Neurological Science, University of Bologna, Bologna, Italy, ⁵Department of Neuroscience, University of Rome ‘Tor Vergata', Rome, Italy

The autonomic nervous system (ANS) is well known in its peripheral functioning, while its central aspects are still rather obscure. We present here a novel method that, using fMRI and a parasympathetic stimulation of the carotid baroreceptors, allows to investigate brain activity by a direct perturbation of the ANS. We provide here new evidence that ANS perturbation induces expected peripheral responses together with modulation of brain activity in both, regions associated with the autonomic control and regions implicated in higher level functions. Moreover, we show that the parasympathetic stimulation modulates brain networks engaged during high-level cognitive tasks.

Anja Hayen^1,2, Mari Herigstad^1,2, Richard G. Wise³, and Kyle T S Pattinson^1,2
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, United Kingdom, ²Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Oxford, Oxfordshire, United Kingdom, ³School of Psychology, Cardiff University, CUBRIC, Cardiff, United Kingdom

Altered intrathoracic pressure affects cerebral blood flow (CBF) and may confound CBF based measurements of neuronal activity. In 13 healthy human volunteers, with transcranial Doppler (TCD) and ASL, we evaluated the effects of inspiratory and expiratory loading on CBF, and upon the stimulus-evoked CBF response. Transient effects of CBF were observed for 30 seconds following load application that subsequently normalised to baseline. The stimulus-evoked CBF response was unaltered. Therefore, altered intrathoracic pressure seen in respiratory disease is unlikely to adversely affect CBF. We conclude that longer stimulus blocks are better suited for volunteer models investigating neural processing of breathlessness perception.

Ai-Ling Lin¹, Peter Kochunov¹, Peter T Fox¹, Amy Ramage¹, Hsiao-Ying Wey¹, Timothy Q Duong¹, and Douglas Williamson^2
1Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, United States, ²Department of Psychiastry, University of Texas Health Science Center, San Antonio, TX, United States

The purpose of the study was to determine the relationship between the basal cerebral blood flow (CBF), cortical gray matter thickness (GMT) and white matter myelination in adolescents using MRI methods. Our results showed that gray matter pruning and white matter myelination occurred in parallel and the CBF reduction was mainly contributed by the reduced rate of myelination.

David a Ravaee¹, Claudia Huerta¹, Hsiao-Ying Wey¹, Ai-ling Lin¹, and Timothy Duong^1
1University of Texas Health Science Center, San Antonio, TX, United States

This study investigated the relation between perfusion pressure and cerebral blood flow (CBF) in the human brain using MRI during rest and isometric handgrip exercise. Basal CBF was 37 ± 4 mL/100mL/min (N=4). Isometric exercise increased mean CBF, heart rate and mean arterial pressure (P<0.05), but not O2 saturation, end tidal CO2, or respiratory rate (P>0.1). A MRI approach provides objective quantitative CBF with a large field of view without depth limitation. fMRI during isometric exercise provides a unique means to study brain physiology and autoregulation free of potential adverse pharmacological effects.

Kuang-Chi Tung¹, Feng Xu¹, Jinsoo Uh¹, and Hanzhang Lu^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Brain¡¯s plasticity forms the basis of many of our daily functions including memory and learning. However, the exact neuronal processes that underlie the plasticity are poorly understood. The present elucidated the temporal course functional connectivity in response to training and its return to baseline level upon training termination. These data suggest that the brain is constantly re-organizing itself based on life experiences and that a short-duration task is sufficient to leave a ¡°foot-print¡± on the brain. However, if not maintained or consolidated, such alterations will disappear within a matter of a few minutes.

Mark Chiew^1,2, Stephen M LaConte³, and Simon James Graham^1,4
1Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ²Rotman Research Institute, Toronto, Ontario, Canada, ³School of Biomedical Engineering, Virginia Tech, Blacksburg, Virginia, United States, ⁴Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Neurofeedback (NF) using real-time functional magnetic resonance imaging (fMRI) is an emerging technique for the self regulation of brain activity, and has been shown to be successful in motor imagery applications. However, in imagined hand motor activity NF experiments on young healthy adults, we show that there is a large range of NF ability observed across the subjects. Here we use a behavioural partial least squares (PLS) analysis to investigate the spatial distribution of brain differences during NF with respect to performance, to identify regions and networks that mediate successful self-regulation.

Vincent Jerome Schmithorst¹, and Scott Kerry Holland^1
1Radiology, Children's Hospital Medical Center, Cincinnati, OH, United States

To date, there is no published data examining between-group racial differences in the neurobiological correlates of intelligence. We performed a retrospective analysis of fMRI data obtained as part of a study of normal language development in children ages 5-18 to investigate this question. In a cohort of African-American and Caucasian children matched for IQ, age, and socio-economic status, specific regions with race-X-IQ interactions on brain activation were found on two out of the four tasks examined. Results suggest such differences are subtle and not widespread and may relate to differences in the relation between executive function and intelligence.

Monia Cabinio^1,2, Gabriella Cerri³, Paola Borroni⁴, Valeria Blasi¹, Antonella Iadanza¹, and Andrea Falini^1,2
1Neuroradiology - CERMAC, San Raffaele Scientific Institute, Milan, Italy, ²Vita-Salute San Raffaele University, Milan, Italy, ³Department of Human Physiology, University of Milan, Milan, Italy,⁴Department of Medicine, Surgery and Dental Sciences, University of Milan, Milan, Italy

Mirror Neurons are bimodal neurons active both during action observation and execution. In humans the observation of actions induces the activation of a fronto-parietal network (Mirror Neuron System, MNS). Some authors found that BA44, a fundamental language area, is part of the MNS. This evidence lead to the hypothesis that MNS is important in the evolution of language. However this data is controversial. With this work we assess if BA44 is active during observation/execution of hand and mouth movements. We did not find activation of BA44 for hand actions and only a minimal, if any, involvement for mouth actions, thus challenging the over mentioned theory.

Yunqing Li^1,2, Prasanna Karunanayaka¹, Jianli Wang¹, Paul J Eslinger³, Dana M Lochman¹, Ping Li⁴, and Qing Yang^1,5
1Radiology, The Pennsylvania State University, Hershey, Pennsylvania, United States, ²Radiology, Tianjin Medical University, Tianjin, China, People's Republic of, ³Neural & Behavioral Sciences, The Pennsylvania State University, Hershey, Pennsylvania, United States, ⁴Psychology, The Pennsylvania State University, University Park, Pennsylvania, United States, ⁵Neurosurgery, The Pennsylvania State University, Hershey, Pennsylvania, United States

Lexical-semantic knowledge undergoes prolonged developmental changes throughout childhood and provides an ideal case for developmental research. Both neuropsychological and fMRI investigations of verbal fluency have been widely used to evaluate language and executive control processes in the human cortex. Our findings show that both the location and amount of cortical activity associated with Lexical-semantic tasks can be modulated by varying the task demands of the verbal fluency paradigm. These results provide convincing evidence for brain connectivity differences in neural networks subserving verbal fluency, depending upon efficient task initiation, planning, organization, and flexibility.

Fabian Grabenhorst¹, Stefan Maderwald², Frank P. Schulte^2,3, and Matthias Brand^2,3
1University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom, ²Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany,³University Duisburg-Essen, General Psychology: Cognition, Duisburg, Germany

High-field MRI at 7T inherently offers higher signal-to-noise and enhanced soft tissue as well as BOLD contrasts compared to 1.5T or even 3T. Here we used 7T functional MRI to investigate neural representations of valuation and decision variables while subjects performed a food evaluation task. We identified neural representations of key valuation and decision variables such as subjective taste pleasantness and decision confidence in different parts of the brain’s valuation system including orbitofrontal, dorsolateral and ventromedial prefrontal cortex, amygdala and striatum. Our results demonstrate that reward-related effects can be detected with 7T fMRI even simultaneously in anatomically separate artifact-prone areas.

Seok-kyun Oh¹, Gwang-Won Kim², Jong-Chul Yang³, Seok-Kwun Kim⁴, and Gwang-Woo Jeong^2,5
1Research Institute for Medical Imaging (RIMI), Department of Radiology, Chonnam National University Hospital, Gwangju, Korea, Republic of, ²Interdisciplinary Program of Biomedical Engineering, Chonnam National University, Gwangju, Korea, Republic of, ³Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea, Republic of, ⁴Department of Plastic and Reconstructive Surgery, Dong-A University College of Medicine, Busan, Korea, Republic of, ⁵Department of Radiology, Chonnam National University Medical School and Hospital, Gwangju, Korea, Republic of

Transsexualism is a type of the gender identity disorder and it is defined by a desire to be accepted as a member of the opposite sex. Neuroimaging studies for the male-to-female (MTF) transsexuals with a sex reassignment surgery and hormone supplementary therapy have not yet been reported. This study utilized a functional magnetic resonance imaging (fMRI) to contrast the differential brain activation patterns in response to visual stimulation with each male and female erotic nude pictures in MTF transsexuals.

Jeong-Won Jeong¹, Vaibhav Diwadkar², Carla D. Chugani³, Harry T. Chugani⁴, and Diane C. Chugani^5
1Pediatrics, Neurology, Wayne State University, Detroit, Michigan, United States, ²Psychiatry, Behavioral Neuroscience, Wayne State University, Detroit, Michigan, United States, ³Florida Gulf Coast University, ⁴Pediatrics, Neurology, Radiology, Wayne State University, Detroit, Michigan, United States, ⁵Pediatrics, Radiology, Wayne State University, Detroit, Michigan, United States

Emotional cues from the environment are obtained through multiple sensory modalities, and the integration of these emotionally laden sensory signals might enhance or diminish the emotional experience conveyed by each sense alone. This study hypothesizes that neural mechanisms involved in listening to music may differ when presented together with visual stimuli that conveyed the same emotion as the music when compared to visual stimuli with incongruent emotional content. Based on above hypothesis, we present a novel functinal MRI paradigm combining happy and sad music with happy and sad faces to examine the response of superior temporal gyrus (STG) and fusiform gyrus (FG).

Rasmus Matthias Birn¹, Steven E Shelton¹, Jonathan A Oler¹, Andrew S Fox², Richard J Davidson^1,2, and Ned H Kalin^1
1Department of Psychiatry, University of Wisconsin, Madison, WI, United States, ²Department of Psychology, University of Wisconsin, Madison, WI, United States

In this study we investigate the resting-state functional connectivity of the amygdala and its relation to individual differences in anxious temperament (AT) in a large cohort of young rhesus macaque monkeys (n=107). Significant functional connectivity was found between the right central nucleus of the amygdala (CeA ; where PET imaging shows correlation between metabolism and AT) and left amygdala, bilateral dorsolateral prefrontal cortex (dlPFC), ventromedial prefrontal cortex, and bilateral bed nucleus of the stria terminalis (BNST) regions. Across subjects, AT was significantly correlated with the functional connectivity between right CeA and right dlPFC with more anxious subjects exhibiting lower connectivity.

Hsiao-Ying Wey^1,2, Angela R. Laird^1,2, Peter T. Fox^1,2, and Timothy Q. Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Resting-state networks also exist in nonhuman primates. Due to the nature of resting-state data (lack of external stimuli or goal-directed behavior) and the difficulties to map brain functions by evoked responses in nonhuman primates, we explored the possibility to provide functional interpretations of resting-state networks in baboons by finding spatially similar functional networks in humans with known behavioral domains.

Yen-Yu Ian Shih¹, Shiliang Huang¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Subcortical activation in anesthetized animal models is challenging. This study introduces a novel approach to evoke negative fMRI response in the rat striatum using forepaw stimulation under isoflurane anesthesia, allowing longitudinal investigation of striatal function. The fMRI responses to nine different stimulus pulse durations of forepaw were analyzed. Robust positive fMRI responses were observed in the contralateral primary somatosensory cortex, but bilateral negative fMRI responses were observed in the striatum. We also demonstrate this approach on a unilateral focal ischemia. Our findings make survival animal fMRI with robust subcortical responses become reality.

Yen-Yu Ian Shih¹, Bryan H De La Garza¹, Eric R Muir¹, Li Guang¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

This study reports a novel application of very high resolution (60 µm) fMRI using MION at an 11.7 T scanner to image the rat retina associated with various visual stimulations. The retinal layer responses to flickering light of different luminance, frequency and wavelength were greater than in the choroidal layer. The retinal layer responses were dependent on luminance, frequency and wavelength revealing characteristic tuning curves, whereas the outer layer responses were not, suggesting differential neurovascular coupling between the two vascular layers. This is the first report of vascular layer-specific fMRI during visual stimulation in the retina in vivo.

Ai-Ling Lin¹, Peter T Fox¹, Holly Van Remmen², Arlan G Richardson², and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, United States, ²Barshop Institute for Logevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, United States

Increased lifespan is observed in mice with a mitochondrial mutation in an assembly protein (Surf1 knockout; Surf1-/-) for electron-transport-chain complex IV, which results in a reduction in the level of cytochrome c oxidase (COX). The pupose of the study, therefore, was to determine the basal flo-metabolism coupling relationship and the metabolic pathway in the Surf1-/- mice. Cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRGlc) were measured with MRI and PET, respectively. The results showed that basal flow and metabolism were uncoupled in the Surf1-/- mice (the basal CBF of the Surf1-/- was observed 20% lower than that of the WT (P < 0.05), while the cerebral glucose uptake of the Surf1-/- mice increased 85% compared to the WT (P < 0.001). The data further demonstrated that the metabolic pathway of the Surf1-/- mice has shifted from oxidative to glycolytic metabolism (with decreased oxygen consumption, but with increased glucose uptake).

Yoshiyuki Hirano¹, Junjie Liu¹, and Afonso C Silva^1
1Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

The use of fMRI to understand the cortical representation of tactile information of the hands is of current interest. Here, we used BOLD fMRI to measure the hemodynamic response to unilateral and bilateral somatosensory stimulation paradigms in awake marmosets. Robust responses were obtained in contralateral SI to 4 and 40 Hz unilateral stimulation. However, the ipsilateral cortex yielded negative and positive responses, respectively. Moreover, bilateral stimuli produced positive responses of higher amplitudes than the summation of the responses to unilateral stimuli. These findings suggest that bilateral stimulation always facilitates the hemodynamic response in S1 through transcallosal interactions.

Nathalie Just^1,2, Carl Petersen³, and Rolf Gruetter^1,4
1LIFMET, CIBM/EPFL, Lausanne, Switzerland, ²Department of Radiology, UNIL, Lausanne, Switzerland, ³LSENS, EPFL, Lausanne, Switzerland, ⁴Department of Radiology, UNIL& HUG, Lausanne & Geneve, Switzerland

The barrel cortex of the rodent represents the equivalent of the visual area in humans. The mouse barrel cortex is highly organized for processing somatosensory information and represents an attractive model for the development of functional Magnetic Resonance Imaging methods of small structures. However, MR functional investigations remain challenging due to a poor signal to noise ratio. In the present study, we propose to address the feasibility of high field fMRI methods to obtain BOLD responses in the mouse barrel cortex following electrical stimulation of the whisker pad under controlled physiological conditions.

Hsiao-Ying Wey^1,2, Peter Kochunov^1,2, Peter T. Fox^1,2, Angela R. Laird^1,2, and Timothy Q. Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Radiology, University of Texas 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 networks in a large nonhuman primate (baboons, Old World monkeys) who is evolutionary close to humans, and we compared the similarities and discrepancies with networks found in humans. We observed similar networks associated with primary functions in both species, however, networks were more asymmetric in baboons.

Fuqiang Zhao¹, Denise Welsh¹, Mangay Williams¹, Hongyu Annie Liang², Alexandre Coimbra¹, Mark O. Urban², Mark Bowlby², Richard Hargreaves², Jeffrey L Evelhoch¹, and Donald S Williams^1
1Imaging, Merck, West Point, PA, United States, ²Neuroscience, Merck, West Point, PA, United States

Pregabalin (Lyrica) is used for the treatments of epilepsy and pain. Both its anatomical targets and its mechanism of action are poorly understood. In this study, the suppression effects of pregabalin on noxious electrical stimulation (NES) induced responses were investigated by BV fMRI in anesthetized rats, and by behavioral assay (vocalization) in awake rats. Our fMRI and behavioral results suggest that 1) pregabalin has efficacy on NES-induced pain in naïve rats; and 2) the analgesic action sites of pregabalin are not in the primary somatosensory pathway (spinal cord, dorsal column nuclei, thalamic relay, S1), but in other activated regions.

Jack B Stephenson, IV¹, Rupeng Li², Patrick Hettinger¹, Matthew Runquist², Christopher P Pawela², Ji Geng Yan¹, Hani Matloub¹, and James Hyde^2
1Plastic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

It is unclear how the brain is affected after C7 root coaptation in brachial plexus nerve transfer procedures. In this 9.4T BOLD-fMRI rat survival study, the cortices of healthy and donor C7 rat brains are compared using images and voxel counting. Preliminary results show early decreased activation in donor rats' sensorimotor cortex.

Simone Claudia Bosshard¹, Florian Stuker¹, Constantin von Deuster¹, and Markus Rudin^1,2
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Institute of Pharmacology and Toxicology, University Zürich, Zurich, Switzerland

To study nociceptive processing in mice, a thermal stimulation paradigm using an infrared laser source for forepaw stimulation was developed. The skin of the forepaws was heated to 45°C or 46°C for 60s, using a feedback system to control the temperature. The stimulation led to significant BOLD changes in the somatosensory cortex and the thalamus. For modulation, a combination of QX-314 and capsaicin was injected into the forepaws, inducing a selective nociceptor block, which led to an abolishment of the BOLD signal. Either solution applied alone did not lead to a decrease in BOLD signal changes.

Juha-Pekka Niskanen^1,2, Antti M Airaksinen¹, Alejandra Sierra¹, Joanna K Huttunen¹, Pasi A Karjalainen², Jari Nissinen¹, Asla Pitkänen^1,3, and Olli Gröhn^1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ²Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland, ³Department of Neurology, Kuopio University Hospital, Kuopio, Finland

Previously, we have detected deficit and recovery of the rat somatosensory BOLD response following TBI, although SI appeared normal in structural MRI. To further investigate this phenomenon, simultaneous LFP/fMRI and histology were performed 2 and 35 days after TBI in rats. The ipsilateral BOLD and LFP responses were lost at 2d, but only partially at 35d. Furthermore, histology revealed gliosis in the ipsilateral ventral posterolateral (VPL) thalamic nucleus. Our results show that hemodynamic uncoupling is not the cause for the detected functional deficit in the rat SI after TBI, but rather neurodegeneration in the thalamic VPL.

S K Hekmatyar¹, Madhu M Keralapurath², Jason Clark², Sherri Hammond², and John J Wagner^2
1BioImaging Research Center, University of Georgia, Athens, GA, United States, ²Department of Physiology and Pharmacology, University of Georgia, Athens, GA, United States

The temporal pattern of brain activation induced by cocaine in the regions of brain (dHF and vHF) that are associated with memory and learning were studied using functional MRI techniques in three groups of urethane anesthetized (i) cocaine naive (ii) self administered and (iii) in saline injected control rats.

Joanna K Huttunen¹, Antti M Airaksinen¹, Kimmo Lehtimäki², Juha-Pekka Niskanen^1,3, Juha Yrjänheikki², and Olli Gröhn^1
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ²Discovery and Imaging Services, Cerebricon Ltd / Charles River Labs, Kuopio, Finland,³Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland

Detection of small pharmacological responses relies on the stability of the measured signal intensity in time. Calculation of T2 maps from two sequential images diminishes fluctuations in the signal, and therefore allows more subtle activations to be detected. Positive apomorfine responses in T2 maps were detected in the lateral entorhinal cortex with increased T2 values of 3-4 ms. Negative apomorfine responses in T2 maps were detected in the motor cortices with decreased T2 values of 1-2 ms. The T2 map method in pharmacological studies could be beneficial in studying new pharmacological agents with small or unknown responses in the brain.

Fuqiang Zhao¹, Denise Welsh¹, Mangay Williams¹, Hongyu Annie Liang², Alexandre Coimbra¹, Mark O. Urban², Mark Bowlby², Richard Hargreaves², Jeffrey L Evelhoch¹, and Donald S Williams^1
1Imaging, Merck, West Point, PA, United States, ²Neuroscience, Merck, West Point, PA, United States

Anesthesia is necessary for pain fMRI studies in animals. The relationship between fMRI responses under anesthesia and behavioral responses in awake animals is unknown. The effect of systemic lidocaine on the pain-induced fMRI signals and on the vocalization threshold was compared. While the pain fMRI signal in the primary somatosensory cortex is not altered, pain signals in all other activated regions were suppressed by lidocaine, with the temporal profiles showing a striking similarity to that for lidocaine-caused behavioral responses. Results suggest that 1) pain fMRI results from anesthetized animals are associated with the behavioral response in awake animals and 2) S1 may not be involved in the pain processing.

Cecil Chern-Chyi Yen¹, Hiro Fukuda², and Seong-Gi Kim^2
1Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ²Neuroimaging Lab Radiology, University of Pittsburgh, Pittsburgh, PA, United States

Neuroscientists have been interested in cortical laminar neural response for decades. If hemodynamic responses are sensitive to laminar neural activity, then high resolution fMRI may provide a non-invasive way to probe these activity. To investigate this issue, we intentionally modulated layer-dependent changes in neural activity during fMRI studies by manipulating the temporal characteristic of the visual stimuli. All laminar response of BOLD or CBV fRMI behaved similarly, even though spiking activity was reported to have different response in lower cortical layer. Our result suggests that it is currently very difficult for hemodynamic-based fMRI to differentiate layer-specific neural activity.

Xin Yu¹, Stephen Dodd¹, Afonso Silva¹, and Alan Koretsky^1
1NINDS, NIH, Bethesda, MD, United States

High spatial resolution EPI images could visualize the intracortical vasculature and allow separation of voxels containing large intracortical veins from surrounding voxels enriched with microvasculature. Early positive BOLD response at 0.8 s following stimulus onset mainly encompassed voxels containing the microvasculature. By 1.6 s activation was more prominent in veins even at cortical layer 4. Functional maps of whisker-row specific barrel areas were clearly separated at 0.8s, but were overlapped by large vessels at later times. These results demonstrate that early positive BOLD fMRI response has better spatial specificity to active regions due to exclusion of contributions from cortical veins.

Nathalie Just¹, and Rolf Gruetter^1
1LIFMET, CIBM/EPFL, Lausanne, Switzerland

In the past, Trigeminal nerve electrical stimulation was shown to be a robust model for the investigation of the BOLD fMRI changes in the rat barrel cortex. In the present study, reproducible BOLD fMRI changes were obtained during sustained 10-minute trigeminal nerve stimulation. Current observations suggest that sustained neuronal activation of the rat barrel cortex permits the investigation of the neurochemical consequences of cortical activation.

Blanca Lizarbe¹, Ania Benitez¹, Pilar Lopez-Larrubia¹, and Sebastian Cerdan^1
1Instituto Investigaciones Biomedicas "Alberto Sols", Madrid, Spain

We investigate the functional mechanisms underlying hypothalamic activation by fasting using Diffusion Weighted MR Imaging. We used eight C57 mice, acquiring DWI from axial sections of the brain containing the hypothalamus, in three orthogonal directions, with increasing diffusion weightings (10b90 and 200b1200), from the same fed or fasted mouse. The data set was fitted to biexponential model yielding parameter values for the relative contributions of the fast (FDP, Dfast) and slow (SDP, Dslow) diffusion phases. Fasting induced, among other effects, a directional dependent increase in the relative contribution of SDP, compatible with neurocellular swelling during activation.