Large dynamic nuclear polarization signal enhancements (up to a factor of 100) were obtained in the solid-state magic-angle spinning nuclear magnetic resonance (NMR) spectra of arginine and the protein T4 lysozyme in frozen glycerol-water solutions with the use of dynamic nuclear polarization. Polarization was transferred from the unpaired electrons of nitroxide free radicals to nuclear spins through microwave irradiation near the electron paramagnetic resonance frequency. This approach may be a generally applicable signal enhancement scheme for the high-resolution solid-state NMR spectroscopy of biomolecules.

DNP (dynamic nuclear polarization) experiments at 5 T are reported, in which a cyclotron resonance maser (gyrotron) is utilized as a 20 W, 140 6Hz microwave source to perform the polarization. MAS (magic angle spinning) NMR spectroscopy with DNP has been performed on samples of polystyrene doped with the free radical BDPA (a, y-bisdiphenylene-P-phenylallyl) at room temperature. Maximal DNP enhancements of -10 for 'H and -40 for ' C are observed and are considerably larger than expected. The DNP and spin relaxation mechanisms that lead to these enhancements at 5 T are discussed.PACS numbers: 76.70.Fz DNP (dynamic nuclear polarization) is a magnetic resonance technique utilized to enhance the polarization of nuclei in samples containing paramagnetic centers [1,2] through irradiation of the electron spins with microwaves in the neighborhood of their Larmor frequency. In studies on solids, this technique has been primarily employed to produce polarized targets for neutron scattering experiments, and to explore magnetic ordering at pK tempera-More recently, DNP has been utilized in high-resolution solid-state NMR (nuclear magnetic resonance) experiments. In MAS (magic angle spinning) NMR spectra, signal enhancements of greater than an order of magnitude have been regularly obtained at room temperature [3][4][5]. Moreover, with high eSciency microwave cavities and with small static samples, enhancements of 50-200 have been achieved [6]. Such enhancements clearly enable significant reductions in the amount of sample or the acquisition time needed to perform an NMR experiment and are therefore of great interest.The utility of these experiments has, however, been limited to date, since they have been performed only at a relatively low field -specifically 1.4 T, corresponding to Larmor frequencies for 'H and electron of coH/2tr= 60 MHz and to, /2tr=40 GHz, respectively. Consequently, the inherent sensitivity and spectral resolution routinely available in high field NMR has not been accessed in DNP-NMR experiments. The restriction to low fields arises mainly from the diSculty in procuring adequate high-power, high-frequency microwave sources. The primary millimeter wave sources, such as the EIO (extended interaction oscillator) or BWO (backward wave oscillator), rely on fragile slow-wave structures to generate microwave radiation, and thus at the high power levels required for DNP experiments have limited operating lifetimes.In the experiments described here, we have surmounted this problem by introducing a cyclotron resonance maser, or gyrotron, as the microwave source. Gyrotrons are presently employed extensively in plasma physics [7]. In the gyrotron, a continuous magnetic field replaces the slow wave structure, and the device is thus capable of generating high microwave powers over a lifetime that is considerably longer than that of an EIO or BWO [8].The microwave frequency of a gyrotron is determined by the applied magnetic field strength and accelerating voltage: gyrotron operation has been demonstrated from 8-600 GHz...

Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degrees C) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum. In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli.

This review and meta-analysis aims at summarizing and integrating the human neuroimaging studies that report periaqueductal gray (PAG) involvement; 250 original manuscripts on human neuroimaging of the PAG were identified. A narrative review and meta-analysis using activation likelihood estimates is included. Behaviors covered include pain and pain modulation, anxiety, bladder and bowel function and autonomic regulation. Methods include structural and functional magnetic resonance imaging, functional connectivity measures, diffusion weighted imaging and positron emission tomography. Human neuroimaging studies in healthy and clinical populations largely confirm the animal literature indicating that the PAG is involved in homeostatic regulation of salient functions such as pain, anxiety and autonomic function. Methodological concerns in the current literature, including resolution constraints, imaging artifacts and imprecise neuroanatomical labeling are discussed, and future directions are proposed. A general conclusion is that PAG neuroimaging is a field with enormous potential to translate animal data onto human behaviors, but with some growing pains that can and need to be addressed in order to add to our understanding of the neurobiology of this key region.

We describe a method that directly relates tissue neuropathological analysis to medical imaging. Presently, only indirect and often tenuous relationships are made between imaging (such as MRI or x-ray computed tomography) and neuropathology. We present a biochemistry-based, quantitative neuropathological method that can help to precisely quantify information provided by in vivo proton magnetic resonance spectroscopy (

Abstract. Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that is used to noninvasively measure cerebral hemoglobin concentration changes induced by brain activation. Using structural guidance in fNIRS research enhances interpretation of results and facilitates making comparisons between studies.AtlasViewer is an open-source software package we have developed that incorporates multiple spatial registration tools to enable structural guidance in the interpretation of fNIRS studies. We introduce the reader to the layout of the AtlasViewer graphical user interface, the folder structure, and user files required in the creation of fNIRS probes containing sources and detectors registered to desired locations on the head, evaluating probe fabrication error and intersubject probe placement variability, and different procedures for estimating measurement sensitivity to different brain regions as well as image reconstruction performance. Further, we detail how AtlasViewer provides a generic head atlas for guiding interpretation of fNIRS results, but also permits users to provide subject-specific head anatomies to interpret their results. We anticipate that AtlasViewer will be a valuable tool in improving the anatomical interpretation of fNIRS studies.

Objective-Focal somatic pain can evolve into widespread hypersensitivity to non-painful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole-body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin.Methods-Extracephalic allodynia was assessed using single unit recording of thalamic trigeminovascular neurons in rats and contrast analysis of BOLD signals registered in fMRI scans of patients exhibiting extracephalic allodynia.Results-Sensory neurons in the rat posterior thalamus that were activated and sensitized by chemical stimulation of the cranial dura exhibited long-lasting hyperexcitability to innocuous (brush, pressure) and noxious (pinch, heat) stimulation of the paws. Innocuous, extracephalic skin stimuli that did not produce neuronal firing at baseline (e.g., brush) became as effective as noxious stimuli (e.g., pinch) in eliciting large bouts of neuronal firing after sensitization was established. In migraine patients, functional MRI assessment of blood oxygenation level-dependent (BOLD) signals showed that brush and heat stimulation at the skin of the dorsum of the hand produced larger BOLD responses in the posterior thalamus of subjects undergoing a migraine attack with extracephalic allodynia than the corresponding responses registered when the same patients were free of migraine and allodynia.Interpretation-We propose that the spreading of multimodal allodynia and hyperalgesia beyond the locus of migraine headache is mediated by sensitized thalamic neurons that process nociceptive information from the cranial meninges together with sensory information from the skin of the scalp, face, body and limbs.

The brain and body respond to potential and actual stressful events by activating hormonal and neural mediators and modifying behaviors to adapt. Such responses help maintain physiological stability ("allostasis"). When behavioral or physiological stressors are frequent and/or severe, allostatic responses can become dysregulated and maladaptive ("allostatic load"). Allostatic load may alter brain networks both functionally and structurally. As a result, the brain's responses to continued/subsequent stressors are abnormal, and behavior and systemic physiology are altered in ways that can, in a vicious cycle, lead to further allostatic load. Migraine patients are continually exposed to such stressors, resulting in changes to central and peripheral physiology and function. Here we review how changes in brain states that occur as a result of repeated migraines may be explained by a maladaptive feedforward allostatic cascade model and how understanding migraine within the context of allostatic load model suggests alternative treatments for this often-debilitating disease.