Oscillatory electroencephalographic (EEG) activity is associated with the excitability of cortical regions. Visual feedback of EEG-oscillations may promote sensorimotor cortical activation, but its ...spatial specificity is not truly guaranteed due to signal interaction among interhemispheric brain regions. Guiding spatially specific activation is important for facilitating neural rehabilitation processes. Here, we tested whether users could explicitly guide sensorimotor cortical activity to the contralateral or ipsilateral hemisphere using a spatially bivariate EEG-based neurofeedback that monitors bi-hemispheric sensorimotor cortical activities for healthy participants. Two different motor imageries (shoulder and hand MIs) were selected to see how differences in intrinsic corticomuscular projection patterns might influence activity lateralization. We showed sensorimotor cortical activities during shoulder, but not hand MI, can be brought under ipsilateral control with guided EEG-based neurofeedback. These results are compatible with neuroanatomy; shoulder muscles are innervated bihemispherically, whereas hand muscles are mostly innervated contralaterally. We demonstrate the neuroanatomically-inspired approach enables us to investigate potent neural remodeling functions that underlie EEG-based neurofeedback via a BCI.
A variety of neural substrates are implicated in the initiation, coordination, and stabilization of voluntary movements underpinned by adaptive contraction and relaxation of agonist and antagonist ...muscles. To achieve such flexible and purposeful control of the human body, brain systems exhibit extensive modulation during the transition from resting state to motor execution and to maintain proper joint impedance. However, the neural structures contributing to such sensorimotor control under unconstrained and naturalistic conditions are not fully characterized. To elucidate which brain regions are implicated in generating and coordinating voluntary movements, we employed a physiologically inspired, two-stage method to decode relaxation and three patterns of contraction in unilateral finger muscles (i.e., extension, flexion, and co-contraction) from high-density scalp electroencephalograms (EEG). The decoder consisted of two parts employed in series. The first discriminated between relaxation and contraction. If the EEG data were discriminated as contraction, the second stage then discriminated among the three contraction patterns. Despite the difficulty in dissociating detailed contraction patterns of muscles within a limb from scalp EEG signals, the decoder performance was higher than chance-level by 2-fold in the four-class classification. Moreover, weighted features in the trained decoders revealed EEG features differentially contributing to decoding performance. During the first stage, consistent with previous reports, weighted features were localized around sensorimotor cortex (SM1) contralateral to the activated fingers, while those during the second stage were localized around ipsilateral SM1. The loci of these weighted features suggested that the coordination of unilateral finger muscles induced different signaling patterns in ipsilateral SM1 contributing to motor control. Weighted EEG features enabled a deeper understanding of human sensorimotor processing as well as of a more naturalistic control of brain-computer interfaces.
•We evaluated spatial-filtering of EEG sensorimotor rhythm via simultaneous EEG-fMRI.•Sensitivity was judged by the number of statistically significant voxels in the sensorimotor cortex.•Specificity ...was evaluated by the proportion of statistically significant voxels in the sensorimotor and visual cortices.•Common average reference and large-Laplacian filters best reflected sensorimotor activity.
Oscillations in the resting-state scalp electroencephalogram (EEG) represent various intrinsic brain activities. One of the characteristic EEG oscillations is the sensorimotor rhythm (SMR)—with its arch-shaped waveform in alpha- and betabands—that reflect sensorimotor activity. The representation of sensorimotor activity by the SMR depends on the signal-to-noise ratio achieved by EEG spatial filters.
We employed simultaneous recording of EEG and functional magnetic resonance imaging, and 10-min resting-state brain activities were recorded in 19 healthy volunteers. To compare the EEG spatial-filtering methods commonly used for extracting sensorimotor cortical activities, we assessed nine different spatial-filters: a default reference of EEG amplifier system, a common average reference (CAR), small-, middle- and large-Laplacian filters, and four types of bipolar manners (C3-Cz, C3-F3, C3-P3, and C3-T7). We identified the brain region that correlated with the EEG-SMR power obtained after each spatial-filtering method was applied. Subsequently, we calculated the proportion of the significant voxels in the sensorimotor cortex as well as the sensorimotor occupancy in all significant regions to examine the sensitivity and specificity of each spatial-filter.
The CAR and large-Laplacian spatial-filters were superior at improving the signal-to-noise ratios for extracting sensorimotor activity from the EEG-SMR signal.
Our results are consistent with the spatial-filter selection to extract task-dependent activation for better control of EEG-SMR-based interventions. Our approach has the potential to identify the optimal spatial-filter for EEG-SMR.
Evaluating spatial-filters for extracting spontaneous sensorimotor activity from the EEG is a useful procedure for constructing more effective EEG-SMR-based interventions.
Human behavior requires inter-regional crosstalk to employ the sensorimotor processes in the brain. Although external neuromodulation techniques have been used to manipulate interhemispheric ...sensorimotor activity, a central controversy concerns whether this activity can be volitionally controlled. Experimental tools lack the power to up- or down-regulate the state of the targeted hemisphere over a large dynamic range and, therefore, cannot evaluate the possible volitional control of the activity. We addressed this difficulty by using the recently developed method of spatially bivariate electroencephalography (EEG)-neurofeedback to systematically enable the participants to modulate their bilateral sensorimotor activities. Here, we report that participants learn to up- and down-regulate the ipsilateral excitability to the imagined hand while maintaining constant contralateral excitability; this modulates the magnitude of interhemispheric inhibition (IHI) assessed by the paired-pulse transcranial magnetic stimulation (TMS) paradigm. Further physiological analyses revealed that the manipulation capability of IHI magnitude reflected interhemispheric connectivity in EEG and TMS, which was accompanied by intrinsic bilateral cortical oscillatory activities. Our results show an interesting approach for neuromodulation, which might identify new treatment opportunities, e.g., in patients suffering from a stroke.
The microRNA (miRNA) processing enzyme Dicer1 is required for zygotic and embryonic development, but the early embryonic lethality of Dicer1 null alleles in mice has limited our ability to address ...the role of Dicer1 in normal mouse growth and development. To address this question, we used a mouse mutant with a hypomorphic Dicer1 allele (Dicer(d/d)) and found that Dicer1 deficiency resulted in female infertility. This defect in female Dicer(d/d) mice was caused by corpus luteum (CL) insufficiency and resulted, at least in part, from the impaired growth of new capillary vessels in the ovary. We found that the impaired CL angiogenesis in Dicer(d/d) mice was associated with a lack of miR17-5p and let7b, 2 miRNAs that participate in angiogenesis by regulating the expression of the antiangiogenic factor tissue inhibitor of metalloproteinase 1. Furthermore, injection of miR17-5p and let7b into the ovaries of Dicer(d/d) mice partially normalized tissue inhibitor of metalloproteinase 1 expression and CL angiogenesis. Our data indicate that the development and function of the ovarian CL is a physiological process that appears to be regulated by miRNAs and requires Dicer1 function.
Objective. A critical feature for the maintenance of precise skeletal muscle force production by the human brain is its ability to configure motor function activity dynamically and adaptively in ...response to visual and somatosensory information. Existing studies have concluded that not only the sensorimotor area but also distributed cortical areas act cooperatively in the generation of motor commands for voluntary force production to the desired level. However, less attention has been paid to such physiological mechanisms in conventional brain-computer interface (BCI) design and implementation. We proposed a new, physiologically inspired two-stage decoding method to see its contribution on accuracy improvement of BCI. Approach. We performed whole-head high-density scalp electroencephalographic (EEG) recording during a right finger force-matching task at three strength levels (20%, 40%, and 60% maximal voluntary contraction following a resting state). A two-stage regression approach was employed that decodes muscle contraction level from EEG signals in the multi-level force-matching task and translates them into: (1) presence/absence of muscle contraction as a first stage; and (2) muscle contraction level as a second stage. Dimensionality reduction of the EEG signals, using principal component analysis, avoided multicollinearity during multiple regression, and data-driven stepwise multiple regression identified EEG components that were involved in the multi-level force-matching task. Main results. An alternatively tuned two-stage regressor accurately decoded muscle contraction level with online processing rather than the conventional decoders, and identified EEG components that were related to voluntary force production. Relaxation/contraction state-dependent EEG components were localized dominantly in the contralateral parieto-temporal regions, whereas multi-level force regulation-dependent EEG components came from the fronto-parietal regions. Significance. Our findings identify respective cortical signalings during relaxation/contraction and multi-level force regulation using a sensor-based approach with EEG. Simulation-based assessment of the current physiologically inspired decoding technique proved improved accuracy in online BCI control.
Mitogen-activated protein (MAP) kinase cascades play a central role in mediating extracellular stimuli-induced intracellular signaling during cell activation. The fourth and least studied mammalian ...MAP kinase pathway, big MAP kinase 1 (BMK1), also known as extracellular signal regulated kinase 5 (ERK5), is activated in response to growth factors and stress. Activation of this signaling pathway has been implicated not only in physiological functions such as cell survival, proliferation and differentiation but also in pathological processes such as carcinogenesis, cardiac hypertrophy and atherosclerosis. In recent years a series of gene-targeted mice lacking components within the BMK1 cascade have been generated, which have enabled us to investigate the role of the BMK1 pathway within different tissues. Analyses of these knockout mice have led to major discoveries in the role of BMK1 signaling in angiogenesis and in cardiac development. Moreover, studies using conditional BMK1 knockout mice, which circumvent the early embryonic lethality of BMK1 knockouts, have unveiled the importance of BMK1 in endothelial survival and maintenance of vascular integrity during adulthood. Here we summarize current understanding of the function of BMK1, as well as include new data generated from a series of tissue-specific BMK1 knockout mice in an attempt to dissect the role of the BMK1 pathway in various cell types in animals.
Paper can be reused to efficiently manage biomass consumption, meaning that it has potential as an environmentally friendly material. On the other hand, because of high energy usage during the ...recycling process and transportation inefficiencies, there is a call for the development of technologies that can mitigate this environmental burden. This study evaluated, from a lifecycle perspective, a new technology that can collect and recycle paper within the office. This technology can reduce by over 90% the amount of water used compared with the conventional recycled paper that is pulped and bleached once by the dry process. It also eliminates transportation from paper collection facilities to recycling factories, reducing greenhouse gas emissions. This new technology is already in use in Japan, and analyses by user data indicate that evaluation results differ greatly depending on the utilization rate of the machine. In the future, environmental information should be shared by both users and manufacturers, so that users could increase their utilization rate, and manufacturers could develop alternative bonding agents in order to further reduce the total environmental burden.
Although big mitogen-activated protein kinase 1 (BMK1) has been shown to be critical for embryonic angiogenesis, the role of BMK1 in tumor-associated neovascularization is poorly understood. ...Exogenous tumors were established in BMK1+/+, BMK1flox/+, or BMK1flox/flox mice carrying the Mx1-Cre transgene. Induced deletion of host BMK1 gene significantly reduced the volumes of B16F10 and LL/2 tumor xenografts in BMK1flox/flox mice by 63% and 72%, respectively. Examining the tumors in these induced BMK1-knockout animals showed a significant decrease in vascular density. Localized reexpression of BMK1 in BMK1-knockout mice by administration of adenovirus encoding BMK1 restored tumor growth and angiogenesis to the levels observed in wild-type mice. These observations were further supported by in vivo Matrigel plug assays in which vascular endothelial growth factor- and basic fibroblast growth factor-induced neovacularization was impaired by removing BMK1. Through screening with the Pepchip microarray, we discovered that in BMK1-knockout endothelial cells, phosphorylation of ribosomal protein S6 (rpS6) at Ser235/236 was mostly abrogated, and this BMK1-dependent phosphorylation required the activity of p90 ribosomal S6 kinase (RSK). Immunofluorescent analysis of tumor vasculature from BMK1-knockout and control animals revealed a strong correlation between the presence of BMK1 and the phosphorylation of rpS6 in tumor-associated endothelial cells of blood vessels. As both RSK and rpS6 are known to be important for cell proliferation and survival, which are critical endothelial cell functions during neovascularization, these findings suggest that the BMK1 pathway is crucial for tumor-associated angiogenesis through its role in the regulation of the RSK-rpS6 signaling module.
Many heat-shock proteins (Hsp) are members of evolutionarily conserved families of chaperone proteins that inhibit the aggregation of unfolded polypeptides and refold denatured proteins, thereby ...remedying phenotypic effects that may result from protein aggregation or protein instability. Here we report that the mitochondrial chaperone Hsp40, also known as Dnaja3 or Tid1, is differentially expressed during cardiac development and pathological hypertrophy. Mice deficient in Dnaja3 developed dilated cardiomyopathy (DCM) and died before 10 weeks of age. Progressive respiratory chain deficiency and decreased copy number of mitochondrial DNA were evident in cardiomyocytes lacking Dnaja3. Profiling of Dnaja3-interacting proteins identified the α-subunit of DNA polymerase γ (Polga) as a client protein. These findings suggest that Dnaja3 is crucial for mitochondrial biogenesis, at least in part, through its chaperone activity on Polga and provide genetic evidence of the necessity for mitochondrial Hsp40 in preventing DCM.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK