Neurophysiological Basis of fMRI
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Monday May 9th
Room 510  16:30 - 18:30 Moderators: Galit Pelled and Ed Wu

16:30 100.   The laminar specific neuronal responses to forepaw and optogenetics stimulations   -permission withheld
John Downey1, Nan Li1,2, Assaf A Gilad3,4, Piotr Walczak3,4, Nitish V Thakor2, and Galit Pelled1,3
1F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 2The Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4Cellular Imaging Section, Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Changes in the laminar communication associated with cortical plasticity have been difficult to assess in vivo. Recent advances in optogenetics enable immediate and reversible manipulations of neuronal firing rate by using channelrhodopsin (ChR2). Here we determined the laminar specific neuronal responses in the primary somatosensory cortex (S1) of ChR2 engineered rats. The laminar neuronal responses detected by BOLD fMRI and by local field potentials within S1 were compared between forepaw and ChR2 stimulations. Both forepaw and ChR2 stimulations showed a peak in BOLD and electrophysiology responses in lamina 4, demonstrating the capability of fMRI to resolve optogenetics modulated laminar communication.

16:42 101.   Opto-fmri in awake rodents: activation and deactivation fMRI signals induced by excitation and inhibition of neurons 
Lino Becerra1,2, Gary Brenner2,3, James Bishop1, Pei-Ching Chang1, Hae-Sook Shin3, Aimei Yang4, Michael Baratta4, Patrick Monahan4, Edward Boyden4,5, and David Borsook1,2
1A. Martinos Center, Massachusetts General Hospital, Boston, MA, United States, 2Harvard Medical School, Boston, MA, United States, 3Anesthesiology and Critical Care, Massachusetts General Hospital, Boston, MA, United States, 4Media Laboratory, Massachusetts Institute of Technology, Cambridge, MA, United States, 5Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States

In fMRI studies, positive activation is associated with increased neuronal firing. Negative (deactivation) fMRI BOLD signals have been indirectly associated with inhibition. Using opto-genetic techniques neurons in rat cingulate and somatosensory cortices were trasfected to be photosensitive. Specifically, cingulate neurons were inhibited upon optical stimulation while somatosensory neurons were excited when illuminated. Positive BOLD signal changes were observed in somatosensory cortex while negative ones were observed in cingulate cortex upon illumination. Furthermore, inhibition of cingulate resulted in fMRI activation of other structures. This work confirms that neuronal excitation results in positive BOLD signals and neuronal inhibition produces negative BOLD signals.

16:54 102.   Optogenetics-guided Cortical Plasticity Following Forepaw Denervation  -permission withheld
Nan Li1,2, John Downey1, Amnon Bar-Shir3,4, Assaf A Gilad3,4, Piotr Walczak3,4, Heechul Kim3,4, Suresh E Joel1,3, James J Pekar1,3, Nitish V Thakor2, and Galit Pelled1,3
1F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 2The Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4Cellular Imaging Section, Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Ipsilateral neuronal responses originating from the transcallosal pathway following peripheral nerve injury have been suggested to be negatively correlated to rehabilitation. The goal of this study was to decrease the cortical inhibition in a rat forepaw injury model. The neuronal firing rates in the healthy cortex of halorhodopsin engineered rats were optogeneticly manipulated. Electrophysiology, optical imaging and fMRI were used to evaluate the functional responses. The results demonstrate that decreased in the inhibitory activity within the deprived cortex can be achieved using optogenetics manipulations. This offers novel therapeutic strategies to facilitate rehabilitation.

17:06 103.   Tight Coupling of Resting-state BOLD fluctuations with Intracortical DC Changes in Rat Somatosensory Cortex during Prolonged Medetomidine Sedation 
Wen-ju Pan1, Matthew Magnuson1, Garth Thompson1, Dieter Jaeger2, and Shella Keilholz1
1Biomedical Engineering, Emory University/ Georgia Institute of Technology, Atlanta, GA, United States, 2Biology, Emory University, Atlanta, GA, United States

To investigate the neural correspondence of the resting-state BOLD signal fluctuations, simultaneous fMRI and intracortical electrophysiological recording were performed in rat somatosensory cortex under medetomine sedation. During prolonged medetomine administration (1-6 hours), the BOLD signal in the low frequency powers changed from <0.1-Hz to a combination of <0.1 Hz and a localized peak at 0.2-Hz. The intracortical DC/LFPs were correlated to both peaks of the BOLD signal at a time lag of ~2.5 s.

17:18 104.   Strengthening of Thalamocortical Synapses at Layer IV in the Juvenile Whisker Barrel Measured by MRI and Electrophysiology 
Xin Yu1, Seungsoo Chung1, Shumin Wang1, Stephen Dodd1, Judith Walters1, John Isaac1, and Alan Koretsky1
1NINDS, NIH, Bethesda, MD, United States

In juvenile rats, unilateral infraorbital denervation induces plasticity changes in the whisker-barrel system. Here, we focused on thalamocortical plasticity contralateral to the good whisker pad. Comparison of BOLD-fMRI of cortex and thalamus demonstrated a cortical specific signal increase. Manganese-enhanced MRI was applied to trace thalamocortical connections and estimated an increase of synaptic strength by measuring the transported Mn from thalamus into cortical Layer IV-V. In vitro slice electrophysiological recordings were applied to confirm this synaptic strengthening of the thalamocortical input. Therefore, MRI and electrophysiology indicate that plasticity to strengthen the barrel thalmocortical input occurs in the juvenile rodent.

17:30 105.   Layer-specific interhemispheric functional connectivity in rat S1fl revealed by laminar electrode recordings and resting state fMRI 
Kwangyeol Baek1,2, Woo Hyun Shim1,2, Jaeseung Jeong1, Harsha Radhakrishnan2, Bruce R Rosen2, David A Boas2, Maria Franceschini2, and Young Ro Kim2
1Bio and Brain Engineering, KAIST, Daejeon, Daejeon, Korea, Republic of, 2Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

Recently, spontaneous BOLD fluctuations in MRI have been reported to be correlated between functionally interconnected brain regions. However, it is not yet clear whether such correlation arises from the synchronized neural activity. In the present study, using laminar electrophysiological recordings, we demonstrated spontaneous neural activities in bilateral primary somatosensory cortices (S1) and layer-specific pattern in interhemispheric functional connectivity. Interestingly, similar pattern was replicated in the resting state BOLD MRI. The fine laminar arrangement in the interhemispheric neural connectivity, e.g. corpus callosum, may mediate the interhemispheric neural communication.

17:42 106.   Caffeine-induced Reductions in Motor Connectivity: A Comparison of fMRI and MEG Measures 
Omer Tal1, Chi Wah Wong2, Valur Olafsson2, Mithun Diwakar1,2, Ming-Xiong Huang2, and Thomas T Liu2
1Dept. of Bioengineering, UC San Diego, La Jolla, CA, United States, 2Dept. of Radiology, UC San Diego, La Jolla, CA, United States

Caffeine has previously been shown to reduce the correlation between resting-state BOLD fluctuations in the motor cortex. However, because of the BOLD signal’s dependence on both neural and vascular factors, it is not known to what extent these reductions reflect caffeine’s effect on neural activity as opposed to its effect on the vasculature. In this preliminary study, we use fMRI and magnetoencephalography (MEG) measures to show that caffeine-related decreases in BOLD correlation partially reflect a decrease in neural connectivity.

17:54 107.   Simultaneous intracranial EEG-fMRI in humans suggests that high gamma frequencies are the closest neurophysiological correlate of BOLD fMRI 
David William Carmichael1, Serge Vulliemoz1,2, Roman Rodionov1, Matthew Walker1, Karin Rosenkranz1, Andrew McEvoy3, and Louis Lemieux1,4
1Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, United Kingdom, 2Epilepsy Unit, University Hospital and University of Geneva, Geneva, Switzerland,3Victor Horsley Dept. Neurosurgery, National Hospital for Neurology and Neurosurgery, London, United Kingdom, 4MRI Unit, National Society for Epilepsy, Chalfont St Peter, United Kingdom

We investigated EEG-fMRI coupling in a simple motor task and at rest by simultaneously recording intracranial EEG and fMRI in human sensorimotor cortex. One epilepsy patient, implanted for presurgical evaluation with electrodes covering sensorimotor cortex, was scanned following a strict safety protocol. EEG-frequency specific predictors of the BOLD fMRI response were calculated and correlated with fMRI signal changes from the task-activated sensorimotor region. Our results suggest that high gamma frequencies are the most closely correlated to BOLD-fMRI during the task but not during rest and that the peak correlation frequency is highly dependent on measurement location.

18:06 108.   A simultaneous EEG and high temporal resolution fMRI study of trial-by-trial fluctuations in visual evoked potentials 
Pierre LeVan1, Benjamin Zahneisen1, Thimo Grotz1, and Jürgen Hennig1
1Medical Physics, University Medical Center Freiburg, Freiburg, Germany

This EEG-fMRI study investigates visual evoked potentials (VEP) using MR-encephalography (MREG), an fMRI technique with a high temporal resolution of 100ms. This allows the accurate estimation of the hemodynamic response function (HRF) to visual stimuli, as well as the removal of physiological artifacts. Trial-by-trial fluctuations of the HRF amplitude were correlated with VEP P1 amplitudes at the center of visual cortex, and with N1 amplitudes at the periphery. Moreover, small HRF delay differences consistent with the VEP were observed between P1- and N1-associated brain regions. MREG is a promising technique to study fast neuronal transients with a high temporal resolution.

18:18 109.   Negative BOLD and CBF responses are predicted by natural variations in evoked EEG response to a median nerve stimulus in humans 
Karen J Mullinger1, Stephen D. Mayhew2, Andrew P Bagshaw2, Richard W Bowtell1, and Susan T Francis1
1Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, 2Birmingham University Imaging Centre, School of Psychology, University of Birmingham, Birmingham, United Kingdom

The origins of the negative BOLD response (NBR) remain unclear. Here we use simultaneous EEG-BOLD-ASL recordings during sustained median nerve stimulation to interrogate the NBR. Significant negative correlations of BOLD/CBF with a boxcar model were found in ipsilateral S1. The magnitude of the negative BOLD/CBF responses in ipsilateral S1 were also correlated with the amplitude of somatosensory evoked potentials (SEP) that originated from contralateral S1. This region was more consistent with the site of the positive BOLD in response to the boxcar model in the opposite hemisphere. This study provides new evidence for a neural component underlying the NBR.