NeuroImage
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A specific positron emission tomography (PET) radiotracer for the glycine transporter type 1 (GlyT1) would constitute an imaging biomarker to investigate the distribution of GlyT1 in normal individuals and those with neuropsychiatric disorders. In addition it could demonstrate the ability of a novel drug to reach its target in the brain and enable receptor occupancy studies, thus facilitating drug development. In this article we describe the evaluation in non-human primates of two candidate PET radiotracers ([(11)C]RO5013852 and [(11)C]RO5013853) previously characterized in the rat. ⋯ Plasma concentrations of approximately 150-300 ng/mL were estimated to produce 50% GlyT1 occupancy in the thalamus, the cerebellum and the pons. [(11)C]RO5013853 is a promising radiotracer for in vivo imaging of the GlyT1. It can be easily radiolabeled, exhibits moderate metabolism, displays a good specific signal, and is suitable for receptor occupancy studies of therapeutic compounds that target the GlyT1. The successful characterization of [(11)C]RO5013853 in healthy volunteers is presented in this NeuroImage issue (Wong et al., 2013).
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Quantitative assessment of the myelin content in white matter (WM) using MRI has become a useful tool for investigating myelin-related diseases, such as multiple sclerosis (MS). Myelin water fraction (MWF) maps can be estimated pixel-by-pixel by a determination of the T₂ or T₂* spectrum from signal decay measurements at each individual image pixel. However, detection of parameters from the measured decay curve, assuming a combination of smooth multi-exponential curves, results in a nonlinear and seriously ill-posed problem. ⋯ To determine optimal weighting factors, we define a spatially independent neighborhood for each pixel and a distance with respect to decay rates that effectively includes pixels with similar decay characteristics, and which therefore have similar relaxation parameters. We recover the MWF values by using optimally weighted decay curves. We use numerical simulations and in vitro and in vivo experimental brain data scanned with a multi-gradient-echo sequence to demonstrate the feasibility of our proposed algorithm and to highlight its advantages compared to the conventional method.
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Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 × 1-Ring electrode configuration. ⋯ We provide direct evidence in humans that TES with a 4 × 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 × 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 × 1-Ring montage for cortically targeted neuromodulation.
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Trigeminal neuralgia (TN) is supposedly caused by an ectatic blood vessel affecting the trigeminal nerve at the root entry zone of the brain stem. Recent evidence suggests an additional central component within trigeminal pain-processing in the pathophysiology of TN. Therefore, we aimed to identify specific brain regions possibly associated with the development or maintenance of TN using magnetic resonance imaging (MRI) voxel-based morphometry (VBM). ⋯ No GM increase was found comparing patient subgroups with each other and with healthy controls. The observed changes probably reflect the impact of multiple, daily attacks of trigeminal pain in these patients similar to what was previously described in other chronic pain conditions and may be interpreted as adaptation mechanism to chronic pain in regard to neuronal plasticity. The ACC, parahippocampus and temporal lobe volume reduction in parallel with disease duration may point to a pivotal role of these structures in chronic pain.
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The slow fluctuations of the blood-oxygenation-level dependent (BOLD) signal in resting-state fMRI are widely utilized as a surrogate marker of ongoing neural activity. Spontaneous neural activity includes a broad range of frequencies, from infraslow (<0.5 Hz) fluctuations to fast action potentials. Recent studies have demonstrated a correlative relationship between the BOLD fluctuations and power modulations of the local field potential (LFP), particularly in the gamma band. ⋯ Here we report a first examination of the temporal relation between the resting-state BOLD signal and infraslow LFPs using simultaneous fMRI and full-band LFP recording in rat. The spontaneous BOLD signal at the recording sites exhibited significant localized correlation with the infraslow LFP signals as well as with the slow power modulations of higher-frequency LFPs (1-100 Hz) at a delay comparable to the hemodynamic response time under anesthesia. Infraslow electrical activity has been postulated to play a role in attentional processes, and the findings reported here suggest that infraslow LFP coordination may share a mechanism with the large-scale BOLD-based networks previously implicated in task performance, providing new insight into the mechanisms contributing to the resting state fMRI signal.