1. Low but not high frequency LFP correlates with spontaneous BOLD fluctuations in rat whisker barrel cortex Resting state magnetic resonance imaging (rsMRI) is thought to reflect ongoing spontaneous brain activity. However, the precise neurophysiological basis of rsMRI signal remains elusive. Converging evidence supports the notion that local field potential (LFP) signal in the high frequency range correlates with fMRI response evoked by a task (e.g. visual stimulation). It remains uncertain whether this relationship extends to rsMRI. In this study, we systematically modulated LFP signal in the whisker barrel cortex (WBC) by unilateral deflection of rat whiskers. Results show that functional connectivity between bilateral WBC was significantly modulated at the 2 Hz, but not at the 4 or 6 Hz, stimulus condition. Electrophysiologically, only in the low frequency range (<5 Hz) was the LFP power synchrony in bilateral WBC significantly modulated at 2 Hz, but not at 4 or 6 Hz whisker stimulation, thus distinguishing these two experimental conditions, and paralleling the findings in rsMRI. LFP power synchrony in other frequency ranges was modulated in a way that was neither unique to the specific stimulus conditions nor parallel to the fMRI results. Our results support the hypothesis that emphasizes the role of low frequency LFP signal underlying rsMRI. (Under revision) 2. Resting-state brain networks in the awake marmoset monkey We demonstrated results from small New World monkeys that allows for the characterization of resting-state networks in the awake state. Six adult common marmosets (Callithrix jacchus) were acclimated to light, comfortable restraint using individualized helmets. Following behavioral training, resting BOLD data were acquired during eight consecutive 10 min scans for each conscious subject. Group independent component analysis revealed 12 brain networks that overlap substantially with known anatomically constrained circuits seen in the awake human. Specifically, we found eight sensory and lower order networks (four visual, two somatomotor, one cerebellar, and one caudateputamen network), and four higher-order association networks (one default mode-like network, one orbitofrontal, one frontopolar, and one network resembling the human salience network). In addition to their functional relevance, these network patterns bear great correspondence to those previously described in awake humans. This first-of-its-kind report in an awake New World nonhuman primate model provides a platform for mechanistic neurobiological examination for existing disease models established in the marmoset. (Journal of Neuroscience 33: 16796-16804, 2013) 3. Glutamate mapping using chemical exchange saturation transfer (CEST) imaging Glutamate (Glu) can be potentially mapped using CEST imaging with significantly improved sensitivity compared to conventional MR spectroscopy techniques. However, the Glu signal measured from CEST could be contaminated by contributions from other compounds. We continued the implementation and optimization of the novel glutamate detection method on the 9.4T animal MR scanner. The quantification method to extract Glu signal from other compounds is being developed, and the reliability and accuracy of the new method is being tested. The newly developed method could be a useful tool to observe local transmitter changes in multiple brain regions and their interactions in neurological or psychiatric disorders. 4. Ultra-short TE single-voxel neurochemical profiling techniques MR spectroscopy has the potential to assess neurochemical profiles noninvasively in preclinical models, and can be naturally translated to clinical assessments. We continued the development of ultra-short TE MR spectroscopy techniques on the 9.4T animal MR scanner to measure neurochemical profiles in preclinical models. Specifically, we focused on the development of techniques to suppress signals contributed from macromolecules. Signals from macromolecules (e.g., proteins and membranes) are major challenges in ultra-short TE MR spectroscopy and could lead to inaccurate quantification of compounds such as GABA with lower signal intensities and overlapping frequencies with macromolecules. MR spectroscopy methods to estimate and suppress macromolecular signals were developed and improved accuracy in the quantification of neurochemicals was demonstrated. 5. A functional MRI model of octopus for detecting neuronal electric currents without a blood-oxygen-level-dependent confound Neuronal current MRI (nc-MRI) is an attractive functional MRI technique that directly measures magnetic/electrical signals related to neuronal activity, avoiding from confounds generated by transduction of neurovascular coupling. Despite the efforts that have been devoted to detecting the transient magnetic fields generated by neuronal firing, the conclusion that a functionally relevant signal can be measured with MRI is still controversial. This study investigates the feasibility of detecting a physiologically induced nc-MRI signal in vivo in a blood-oxygen-level-dependent (BOLD) free environment. The cephalopod mollusc Octopus bimaculoides has vertebrate-like eyes, large optic lobes (OLs), and blood that does not contain hemoglobin. Visually evoked potentials were measured in the octopus retina and OL by electroretinogram and local field potential. nc-MRI scans were conducted at 9.4 Tesla to capture these activities. Electrophysiological recording detected strong responses in the retina and OL in vivo;however, nc-MRI failed to demonstrate any statistically significant signal change with a detection threshold of 0.2 for phase and 0.2% for magnitude. Experiments in a dissected eye-OL preparation yielded similar results. These findings in a large hemoglobin-free nervous system suggest that sensory evoked neuronal magnetic fields are too weak for direct detection with current MRI technology. (Magnetic Resonance in Medicine, in press)
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