Neuroscience
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Mitochondrial dysfunction and oxidative stress are very prominent and early features in Parkinson's disease (PD) and in animal models of PD. Thus, antioxidant therapy for PD has been proposed, but in clinical trials such strategies have met with very limited success. Methylene blue (MB), a small-molecule synthetic heterocyclic organic compound that acts as a renewable electron cycler in the mitochondrial electron transport chain, manifesting robust antioxidant and cell energetics-enhancing properties, has recently been shown to have significant beneficial effects in reducing nigrostriatal dopaminergic loss and motor impairment in acute toxin models of PD. ⋯ Oral delivery of low-dose MB significantly ameliorated MPTP/p-induced deficits in motor coordination, as well as degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and TH-positive terminals in the striatum. Importantly, olfactory dysfunction was ameliorated by MB treatment, whereas this benefit is not observed with currently available anti-Parkinsonian medications. These results indicate that low-dose MB is a promising neuroprotective intervention for both motor and non-motor features of PD.
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Hypofunction of NMDA receptors in parvalbumin (PV)-positive interneurons has been proposed as a potential mechanism for cortical abnormalities and symptoms in schizophrenia. GluN2C-containing receptors have been linked to this hypothesis due to the higher affinity of psychotomimetic doses of ketamine for GluN1/2C receptors. However, the precise cell-type expression of GluN2C subunit remains unknown. ⋯ GluN2C was found to be enriched in several first-order and higher order thalamic nuclei. Interestingly, we found that a previous GluN2C β-gal reporter model excluded expression from PV-neurons and certain thalamic nuclei but exhibited expression in the retrosplenial cortex. GluN2C's unique distribution in neuronal and non-neuronal cells in a brain region-specific manner raises interesting questions regarding the role of GluN2C-containing receptors in the central nervous system.
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The ability to update position and orientation to reach a goal is crucial to spatial navigation and individuals vary considerably in this ability. The current structural MRI study used voxel-based morphometry (VBM) analysis to relate individual differences in human brain morphology to performance in an active navigation task that relied on updating position and orientation in a landmark-free environment. Goal-directed navigation took place from either a first person perspective, similar to a person walking through the landmark-free environment, or Survey perspective, a bird's eye view. ⋯ Significant structural volume correlations in the hippocampus, entorhinal cortex, and thalamus were related to first person navigational accuracy. Our results support the theory that hippocampus, entorhinal cortex, and thalamus are key structures for updating position and orientation during ground-level navigation. Furthermore, the results suggest that morphological differences in these regions underlie individual navigational abilities, providing an important link between animal models of navigation and the variability in human navigation.
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Clinical Trial
Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.
Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). ⋯ Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders.
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Motor imagery is the mental process of rehearsing or simulating a given action without overt movements. The aim of the present study is to examine plastic changes in relevant brain areas during motor imagery with increasing expertise level. Subjects (novices, intermediate and elite players) performed motor imagery of basketball throws under two experimental conditions (with-ball and without-ball). ⋯ Importantly, brain activation in the left postcentral gyrus was the highest in the intermediate players compared to both novices and elite players. For the elite group, these three areas showed higher activation in the without-ball condition than the with-ball condition, while the opposite trend was found in intermediate players. Our findings suggest that the level of motor expertise may be related to high-order brain functions that are linked to different activation patterns in different brain areas.