Neuroscience
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We used the framework of the uncontrolled manifold hypothesis to explore force-stabilizing synergies and motor equivalence in the spaces of individual motor unit (MU) firing frequencies. Healthy subjects performed steady force production tasks by pressing with one finger or three fingers of a hand. Surface EMG was used to identify individual MU action potentials. ⋯ Effects of hand dominance were seen on multi-finger synergies but not intra-muscle synergies. We conclude that spinal mechanisms, such as recurrent inhibition and reflex loops from proprioceptors, contribute significantly to intra-muscle synergies, while multi-finger synergies reflect supra-spinal processes. These results provide methods to explore the contributions of spinal vs supraspinal circuitry to changed motor synergies in populations with a variety of neurological disorders.
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Defective mitophagy and mitochondrial dysfunction have been linked to aging and Alzheimer's disease (AD). β2-Adrenergic receptor (ADRB2) is critical for mitochondrial and cognitive function. However, researchers have not clearly determined whether ADRB2 activation ameliorates defective mitophagy and cognitive deficits in individuals with AD. Here, we observed that the activation of ADRB2 by clenbuterol (Clen, ADRB2 agonist, 2 mg/kg/day) ameliorated amyloid-β-induced (Aβ1-42 bilateral intracerebral infusion, 2 μl, 5 μg/μl) memory deficits. ⋯ Finally, we established that Clen improved mitophagy and attenuated mitochondrial dysfunction, and tau pathology in mice by activating the ADRB2/Akt/PINK1 signaling pathway. Conversely, the inhibition of ADRB2 by propranolol (βAR antagonist, 10 μM) blocked the Clen-mediated improvements in pathological changes in N2a cells. The results from the present study indicate that ADRB2 activation may be a therapeutic strategy for AD.
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The relationship of cognitive reserve and measures of reserve with longitudinal cognitive change and the duration of preclinical, prodromal, and mild Alzheimer disease (AD) dementia remains to be fully characterized. In our study, 660 β-amyloid-positive participants staged with preclinical AD, prodromal AD, and dementia due to AD from the Alzheimer's Disease Neuroimaging Initiative were selected. Cognitive reserve and brain reserve were defined by conventional proxies or the residual method at baseline. ⋯ The estimated time from preclinical to mild AD dementia varied from 15-24 years based on the different reserve groups, and we observed a linear trend for the longest duration in individuals with high cognitive reserve/high brain reserve, followed by those with high cognitive reserve/low brain reserve, low cognitive reserve/high brain reserve, and low cognitive reserve/low brain reserve. This study showed a reduced risk of cognitive decline for individuals with higher level of reserve regardless of methods for measuring reserve. Interindividual differences in reserve may be important for clinical practice and trial design.
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Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. ⋯ Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.
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Intelligence is the ability to recognize and understand objective things, and use knowledge and experience to solve problems. Highly intelligent people show the ability to switch between different thought patterns and shift their mental focus. This suggests a link between intelligence and the dynamic interaction of brain networks. ⋯ High variability in these areas indicates flexible connectivity patterns, which may contribute to cognitive processes such as attention selection. In addition, performance intelligence was related to greater temporal variability in the functional connectivity patterns of the salience network. Thus, this study revealed a close relationship between performance intelligence and high variability in brain networks involved in attentional choice, spatial orientation, and cognitive control.