John Downey¹, Nan Li^1,2, Assaf A Gilad^3,4, Piotr Walczak^3,4, Nitish V Thakor², and Galit Pelled^1,3
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.

Lino Becerra^1,2, Gary Brenner^2,3, James Bishop¹, Pei-Ching Chang¹, Hae-Sook Shin³, Aimei Yang⁴, Michael Baratta⁴, Patrick Monahan⁴, Edward Boyden^4,5, and David Borsook^1,2
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.

Nan Li^1,2, John Downey¹, Amnon Bar-Shir^3,4, Assaf A Gilad^3,4, Piotr Walczak^3,4, Heechul Kim^3,4, Suresh E Joel^1,3, James J Pekar^1,3, Nitish V Thakor², and Galit Pelled^1,3
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.

Wen-ju Pan¹, Matthew Magnuson¹, Garth Thompson¹, Dieter Jaeger², and Shella Keilholz^1
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.

Xin Yu¹, Seungsoo Chung¹, Shumin Wang¹, Stephen Dodd¹, Judith Walters¹, John Isaac¹, and Alan Koretsky^1
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.

Kwangyeol Baek^1,2, Woo Hyun Shim^1,2, Jaeseung Jeong¹, Harsha Radhakrishnan², Bruce R Rosen², David A Boas², Maria Franceschini², and Young Ro Kim^2
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.

Omer Tal¹, Chi Wah Wong², Valur Olafsson², Mithun Diwakar^1,2, Ming-Xiong Huang², and Thomas T Liu^2
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.

David William Carmichael¹, Serge Vulliemoz^1,2, Roman Rodionov¹, Matthew Walker¹, Karin Rosenkranz¹, Andrew McEvoy³, and Louis Lemieux^1,4
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.

Pierre LeVan¹, Benjamin Zahneisen¹, Thimo Grotz¹, and Jürgen Hennig^1
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.

Karen J Mullinger¹, Stephen D. Mayhew², Andrew P Bagshaw², Richard W Bowtell¹, and Susan T Francis^1
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.