Existing motor state is favored at the expense of new movement during 13-35 Hz oscillatory synchrony in the human corticospinal system

Oscillations in local field potentials in the β-frequency band (13-35 Hz) are a pervasive feature of human and nonhuman primate motor cortical areas. However, the function of such synchronous activity across populations of neurons remains unknown. Here, we test the hypothesis that β activity may promote existing motor set and posture while compromising processing related to new movements. Three experiments were performed. First, healthy subjects were instructed to make reaction time movements of the outstretched index finger in response to imperative cues triggered by transient increases in corticospinal synchrony, as evidenced by phasic elevations of β-frequency band microtremor and intermuscular synchrony. Second, healthy subjects were instructed to resist a stretch to the index finger triggered in the same way. Finger acceleration in the reaction time task and transcortical components of the stretch reflex were measured and compared with those elicited by random cue or stretch presentation. Finally, we sought a correlation between finger acceleration in the reaction time task and cortical synchrony directly measured from the electrocorticogram in two patients undergoing functional neurosurgery. We demonstrate that movements are slowed and transcortical responses to stretch are potentiated during periods of elevated β-band cortical synchrony. The results suggest that physiological periods of β synchrony are associated with a cortical state in which postural set is reinforced, but the speed of new movements impaired. The findings are of relevance to Parkinson's disease, in which subcortical and cortical β-band synchronization is exaggerated in the setting of increased tone and slowed movements

Penerapan Yoga untuk Mengurangi Nyeri Haid pada Remaja Selama Masa Pandemi Covid-19

Dysmenorrhea or menstrual pain is pain that occurs during menstruation experienced by women of reproductive age.. Acupressure is effective in reducing dysmenorrheal pain. In addition, acupressure is also a therapy that is easy to learn (practical) and safe to overcome dysmenorrhea in adolescents which will be useful for adolescents in order to reduce and overcome dysmenorrhea experienced during menstruation.  Sampling was done by using simple random sampling technique. Random and simple sampling of members of the population.  Adolescent knowledge about dysmenorrhea is quite high 88%, most of them use chemical drugs 42.4%, knowledge about acupressure massage techniques shows low results 0.5.  Many teenagers do not know about acupressure massage techniques to reduce dysmenorrhea. The results of this study hope to add insight to people out there, and can apply acupressure techniques independently at homeAbstrakDismenore atau nyeri haid merupakan nyeri yang terjadi saat menstruasi yang dialami perempuan usia produktif. Akupresur efektif terhadap penurunan nyeri dysmenorhea. Selain itu, akupresur juga merupakan terapi yang mudah dipelajari (praktis) dan aman.  Tujuan kegiatan ini untuk mengatasi dismenore pada remaja yang akan bermanfaat bagi remaja agar bisa mengurangi dan mengatasi dismenore yang dialami saat haid. Pengambilan sampel dilakukan dengan menggunakan teknik simple random sampling. Pengambilan sampel secara acak dan sederhana terhadap anggota populasi.  Pengetahuan remaja tentang dismenore yang cukup tinggi yaitu  88%, sebagian besar mereka menggunakan obat kimiawi  yaitu sekitar 42,4%, pengetahuan mengenai teknik pijat akuprseur menunjukan hasil 0,5%  yaitu rendah.  Banyak remaja yang belum mengetahui mengenai teknik pijat akupresure terhadap pengurangan dismenore. Hasil penelitian ini berharap dapat menambah wawasan orang diluar sana, serta dapat menerapkan teknik akupresure secara mandiri diruma

Penerapan Yoga untuk Mengurangi Nyeri Haid pada Remaja Selama Masa Pandemi Covid-19

Dysmenorrhea or menstrual pain is pain that occurs during menstruation experienced by women of reproductive age.. Acupressure is effective in reducing dysmenorrheal pain. In addition, acupressure is also a therapy that is easy to learn (practical) and safe to overcome dysmenorrhea in adolescents which will be useful for adolescents in order to reduce and overcome dysmenorrhea experienced during menstruation.  Sampling was done by using simple random sampling technique. Random and simple sampling of members of the population.  Adolescent knowledge about dysmenorrhea is quite high 88%, most of them use chemical drugs 42.4%, knowledge about acupressure massage techniques shows low results 0.5.  Many teenagers do not know about acupressure massage techniques to reduce dysmenorrhea. The results of this study hope to add insight to people out there, and can apply acupressure techniques independently at homeAbstrakDismenore atau nyeri haid merupakan nyeri yang terjadi saat menstruasi yang dialami perempuan usia produktif. Akupresur efektif terhadap penurunan nyeri dysmenorhea. Selain itu, akupresur juga merupakan terapi yang mudah dipelajari (praktis) dan aman.  Tujuan kegiatan ini untuk mengatasi dismenore pada remaja yang akan bermanfaat bagi remaja agar bisa mengurangi dan mengatasi dismenore yang dialami saat haid. Pengambilan sampel dilakukan dengan menggunakan teknik simple random sampling. Pengambilan sampel secara acak dan sederhana terhadap anggota populasi.  Pengetahuan remaja tentang dismenore yang cukup tinggi yaitu  88%, sebagian besar mereka menggunakan obat kimiawi  yaitu sekitar 42,4%, pengetahuan mengenai teknik pijat akuprseur menunjukan hasil 0,5%  yaitu rendah.  Banyak remaja yang belum mengetahui mengenai teknik pijat akupresure terhadap pengurangan dismenore. Hasil penelitian ini berharap dapat menambah wawasan orang diluar sana, serta dapat menerapkan teknik akupresure secara mandiri diruma

ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex

Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca2+-dependent mechanism. P2X receptors, co-localized with NMDA receptors in the excitatory synapses, can be activated by ATP co-released with glutamate from pre-synaptic terminals and by glia-derived ATP. An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca2+-dependent de-phosphorylation and interaction with PSD-95 multi-protein complex. Genetic deletion of the PSD-95 or P2X4 receptors obliterated ATP-mediated down-regulation of NMDA receptors. Impairment of purinergic modulation of NMDA receptors in the PSD-95 mutants dramatically decreased the threshold of LTP induction and increased the net magnitude of LTP. Our findings show that synergistic action of glia- and neurone-derived ATP can pre-modulate efficacy of excitatory synapses and thereby can have an important role in the glia-neuron communications and brain meta-plasticity

Plasma membrane cholesterol as a regulator of human and rodent P2X7 receptor activation and sensitization.

P2X7 receptors are nonselective cation channels gated by high extracellular ATP, but with sustained activation, receptor sensitization occurs, whereby the intrinsic pore dilates, making the cell permeable to large organic cations, which eventually leads to cell death. P2X7 receptors associate with cholesterol-rich lipid rafts, but it is unclear how this affects the properties of the receptor channel. Here we show that pore-forming properties of human and rodent P2X7 receptors are sensitive to perturbations of cholesterol levels. Acute depletion of cholesterol with 5 mm methyl-β-cyclodextrin (MCD) caused a substantial increase in the rate of agonist-evoked pore formation, as measured by the uptake of ethidium dye, whereas cholesterol loading inhibited this process. Patch clamp analysis of P2X7 receptor currents carried by Na(+) and N-methyl-D-glucamine (NMDG(+)) showed enhanced activation and current facilitation following cholesterol depletion. This contrasts with the inhibitory effect of methyl-β-cyclodextrin reported for other P2X subtypes. Mutational analysis suggests the involvement of an N-terminal region and a proximal C-terminal region that comprises multiple cholesterol recognition amino acid consensus (CRAC) motifs, in the cholesterol sensitivity of channel gating. These results reveal cholesterol as a negative regulator of P2X7 receptor pore formation, protecting cells from P2X7-mediated cell death.This work was supported by the Biotechnology and Biological Sciences Research Council (BB/F001320/1), the David James Studentship, Department of Pharmacology, University of Cambridge and the Marshall Scholarship.This paper was originally published in The Journal of Biological Chemistry (Robinson LE, Shridar M, Smith P, Murrell-Lagnado RD, The Journal of Biological Chemistry 2014, 289, 46, 31983–31994, doi:10.1074/jbc.M114.574699

Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management.

OBJECTIVE: To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control. RESEARCH DESIGN AND METHODS: This study was a multicenter, randomized, three-way crossover, open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months, treated with continuous subcutaneous insulin infusion. Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara (international artificial pancreas [iAP]), by the algorithm of University of Cambridge (CAM), or by patients themselves in open loop (OL) during three hospital admissions including meals and exercise. The main analysis was on an intention-to-treat basis. Main outcome measures included time spent in target (glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals). RESULTS: Time spent in the target range was similar in CL and OL: 62.6% for OL, 59.2% for iAP, and 58.3% for CAM. While mean glucose level was significantly lower in OL (7.19, 8.15, and 8.26 mmol/L, respectively) (overall P = 0.001), percentage of time spent in hypoglycemia (<3.9 mmol/L) was almost threefold reduced during CL (6.4%, 2.1%, and 2.0%) (overall P = 0.001) with less time ≤2.8 mmol/L (overall P = 0.038). There were no significant differences in outcomes between algorithms. CONCLUSIONS: Both CAM and iAP algorithms provide safe glycemic control

Stress-Dependent Coordination of Transcriptome and Translatome in Yeast

Cells rapidly alter gene expression in response to environmental stimuli such as nutrients, hormones, and drugs. During the imposed “remodeling” of gene expression, changes in the levels of particular mRNAs do not necessarily correlate with those of the encoded proteins, which could in part rely on the differential recruitment of mRNAs to translating ribosomes. To systematically address this issue, we have established an approach to rapidly access the translational status of each mRNA in the yeast Saccharomyces cerevisiae by affinity purification of endogenously formed ribosomes and the analysis of associated mRNAs with DNA microarrays. Using this method, we compared changes in total mRNA levels (transcriptome) with ribosome associations (translatome) after the application of different conditions of cellular stress. Severe stresses, induced by amino acid depletion or osmotic shock, stimulated highly correlated responses affecting about 15% of both total RNA levels and translatome. Many of the regulated messages code for functionally related proteins, thus reflecting logical responses to the particular stress. In contrast, mild stress provoked by addition of Calcofluor-white and menadione altered the translatome of approximately 1% of messages with only marginal effects on total mRNA, suggesting largely uncorrelated responses of transcriptome and translatome. Among these putative translationally regulated messages were most components of the mitochondrial ATPase. Increased polysome associations of corresponding messages and higher mitochondrial ATPase activities upon treatment confirmed the relevance for regulation of this macromolecular complex. Our results suggest the presence of highly sensitive translational regulatory networks that coordinate functionally related messages. These networks are preferentially activated for rapid adaptation of cells to minor environmental perturbations

A torque-based method demonstrates increased rigidity in Parkinson’s disease during low-frequency stimulation

Low-frequency oscillations in the basal ganglia are prominent in patients with Parkinson’s disease off medication. Correlative and more recent interventional studies potentially implicate these rhythms in the pathophysiology of Parkinson’s disease. However, effect sizes have generally been small and limited to bradykinesia. In this study, we investigate whether these effects extend to rigidity and are maintained in the on-medication state. We studied 24 sides in 12 patients on levodopa during bilateral stimulation of the STN at 5, 10, 20, 50, 130 Hz and in the off-stimulation state. Passive rigidity at the wrist was assessed clinically and with a torque-based mechanical device. Low-frequency stimulation at ≤20 Hz increased rigidity by 24 % overall (p = 0.035), whereas high-frequency stimulation (130 Hz) reduced rigidity by 18 % (p = 0.033). The effects of low-frequency stimulation (5, 10 and 20 Hz) were well correlated with each other for both flexion and extension (r = 0.725 ± SEM 0.016 and 0.568 ± 0.009, respectively). Clinical assessments were unable to show an effect of low-frequency stimulation but did show a significant effect at 130 Hz (p = 0.002). This study provides evidence consistent with a mechanistic link between oscillatory activity at low frequency and Parkinsonian rigidity and, in addition, validates a new method for rigidity quantification at the wrist

Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion

A resting state network in the motor control circuit of the basal ganglia

<p>Abstract</p> <p>Background</p> <p>In the absence of overt stimuli, the brain shows correlated fluctuations in functionally related brain regions. Approximately ten largely independent resting state networks (RSNs) showing this behaviour have been documented to date. Recent studies have reported the existence of an RSN in the basal ganglia - albeit inconsistently and without the means to interpret its function. Using two large study groups with different resting state conditions and MR protocols, the reproducibility of the network across subjects, behavioural conditions and acquisition parameters is assessed. Independent Component Analysis (ICA), combined with novel analyses of temporal features, is applied to establish the basis of signal fluctuations in the network and its relation to other RSNs. Reference to prior probabilistic diffusion tractography work is used to identify the basal ganglia circuit to which these fluctuations correspond.</p> <p>Results</p> <p>An RSN is identified in the basal ganglia and thalamus, comprising the pallidum, putamen, subthalamic nucleus and substantia nigra, with a projection also to the supplementary motor area. Participating nuclei and thalamo-cortical connection probabilities allow this network to be identified as the motor control circuit of the basal ganglia. The network was reproducibly identified across subjects, behavioural conditions (fixation, eyes closed), field strength and echo-planar imaging parameters. It shows a frequency peak at 0.025 ± 0.007 Hz and is most similar in spectral composition to the Default Mode (DM), a network of regions that is more active at rest than during task processing. Frequency features allow the network to be classified as an RSN rather than a physiological artefact. Fluctuations in this RSN are correlated with those in the task-positive fronto-parietal network and anticorrelated with those in the DM, whose hemodynamic response it anticipates.</p> <p>Conclusion</p> <p>Although the basal ganglia RSN has not been reported in most ICA-based studies using a similar methodology, we demonstrate that it is reproducible across subjects, common resting state conditions and imaging parameters, and show that it corresponds with the motor control circuit. This characterisation of the basal ganglia network opens a potential means to investigate the motor-related neuropathologies in which the basal ganglia are involved.</p