Probabilistic algorithms for MEG/EEG source reconstruction using temporal basis functions learned from data.

We present two related probabilistic methods for neural source reconstruction from MEG/EEG data that reduce effects of interference, noise, and correlated sources. Both methods localize source activity using a linear mixture of temporal basis functions (TBFs) learned from the data. In contrast to existing methods that use predetermined TBFs, we compute TBFs from data using a graphical factor analysis based model [Nagarajan, S.S., Attias, H.T., Hild, K.E., Sekihara, K., 2007a. A probabilistic algorithm for robust interference suppression in bioelectromagnetic sensor data. Stat Med 26, 3886–3910], which separates evoked or event-related source activity from ongoing spontaneous background brain activity. Both algorithms compute an optimal weighting of these TBFs at each voxel to provide a spatiotemporal map of activity across the brain and a source image map from the likelihood of a dipole source at each voxel. We explicitly model, with two different robust parameterizations, the contribution from signals outside a voxel of interest. The two models differ in a trade-off of computational speed versus accuracy of learning the unknown interference contributions. Performance in simulations and real data, both with large noise and interference and/or correlated sources, demonstrates significant improvement over existing source localization methods

MEG/EEG source reconstruction, statistical evaluation, and visualization with NUTMEG.

NUTMEG is a source analysis toolbox geared towards cognitive neuroscience researchers using MEG and EEG, including intracranial recordings. Evoked and unaveraged data can be imported to the toolbox for source analysis in either the time or time-frequency domains. NUTMEG offers several variants of adaptive beamformers, probabilistic reconstruction algorithms, as well as minimum-norm techniques to generate functional maps of spatiotemporal neural source activity. Lead fields can be calculated from single and overlapping sphere head models or imported from other software. Group averages and statistics can be calculated as well. In addition to data analysis tools, NUTMEG provides a unique and intuitive graphical interface for visualization of results. Source analyses can be superimposed onto a structural MRI or headshape to provide a convenient visual correspondence to anatomy. These results can also be navigated interactively, with the spatial maps and source time series or spectrogram linked accordingly. Animations can be generated to view the evolution of neural activity over time. NUTMEG can also display brain renderings and perform spatial normalization of functional maps using SPM's engine. As a MATLAB package, the end user may easily link with other toolboxes or add customized functions

The relationship between magnetic and electrophysiological responses to complex tactile stimuli.

Background Magnetoencephalography (MEG) has become an increasingly popular technique for non-invasively characterizing neuromagnetic field changes in the brain at a high temporal resolution. To examine the reliability of the MEG signal, we compared magnetic and electrophysiological responses to complex natural stimuli from the same animals. We examined changes in neuromagnetic fields, local field potentials (LFP) and multi-unit activity (MUA) in macaque monkey primary somatosensory cortex that were induced by varying the rate of mechanical stimulation. Stimuli were applied to the fingertips with three inter-stimulus intervals (ISIs): 0.33s, 1s and 2s. Results Signal intensity was inversely related to the rate of stimulation, but to different degrees for each measurement method. The decrease in response at higher stimulation rates was significantly greater for MUA than LFP and MEG data, while no significant difference was observed between LFP and MEG recordings. Furthermore, response latency was the shortest for MUA and the longest for MEG data. Conclusion The MEG signal is an accurate representation of electrophysiological responses to complex natural stimuli. Further, the intensity and latency of the MEG signal were better correlated with the LFP than MUA data suggesting that the MEG signal reflects primarily synaptic currents rather than spiking activity. These differences in latency could be attributed to differences in the extent of spatial summation and/or differential laminar sensitivity

A RANDOMIZED CLINICAL ENDPOINT STUDY TO EVALUATE THE SAFETY AND EFFICACY OF CLEARLIV TABLETS IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

Objective: The objective of this study was to evaluate and compare the hepatoprotective effect of clearliv tablets with silymarin in patients with alcoholic liver disease.Methods: This was a prospective, randomized, multicenter, open-label, parallel group interventional clinical endpoint study (Phase IIa). Patients attending general medicine outpatient department were screened for alcoholic liver disease using the serum biochemical liver function test and ultrasonogram abdomen and tested whether they satisfy the selection criteria, and 24 patients were then enrolled in the study. The study drug, namely clearliv tablets of Apex Laboratories Pvt. Ltd., was administered to Group A and tablet silymarin was administered to Group B from day 1 to day 56. Patients were reviewed once in 2 weeks. Liver function test was repeated, and patients were enquired of their well-being and any adverse events.Results: The demographic characters and body weight of the subjects showed no significant difference between the groups. There is a significant improvement (p<0.05) in the aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin (TB) levels on 28th and 56th days in both silymarin and clearliv groups. Of the 2 groups, there is higher significance of improvement in clearliv group (p<0.001), compared to silymarin group. Clearliv group started showing a significant reduction in AST and ALT levels in the first 14 days of the study period. On comparing the mean percentage reduction in the levels of AST (35.7% and 35%), ALT (26.7% and 24.3%), and TB (26.7% and 25%), it was found that clearliv is showing a better percentage of reduction of the above parameters compared to silymarin. There were reports of adverse effects such as loss of appetite and gastritis in both the groups.Conclusion: This clinical study proves that clearliv is functioning as a hepatoprotective drug. It is offering a better hepatoprotection compared to silymarin. Clearliv tablets can be indicated for the management of liver dysfunction, which occurs due to alcoholic liver damage. It may also be used in similar manner in cases of viral hepatitis, drug-induced liver damage, acute and chronic hepatitis

Can ultrasound be used to stimulate nerve tissue?

BACKGROUND: The stimulation of nerve or cortical tissue by magnetic induction is a relatively new tool for the non-invasive study of the brain and nervous system. Transcranial magnetic stimulation (TMS), for example, has been used for the functional mapping of the motor cortex and may have potential for treating a variety of brain disorders. METHODS AND RESULTS: A new method of stimulating active tissue is proposed by propagating ultrasound in the presence of a magnetic field. Since tissue is conductive, particle motion created by an ultrasonic wave will induce an electric current density generated by Lorentz forces. An analytical derivation is given for the electric field distribution induced by a collimated ultrasonic beam. An example shows that peak electric fields of up to 8 V/m appear to be achievable at the upper range of diagnostic intensities. This field strength is about an order of magnitude lower than fields typically associated with TMS; however, the electric field gradients induced by ultrasound can be quite high (about 60 kV/m(2 )at 4 MHz), which theoretically play a more important role in activation than the field magnitude. The latter value is comparable to TMS-induced gradients. CONCLUSION: The proposed method could be used to locally stimulate active tissue by inducing an electric field in regions where the ultrasound is focused. Potential advantages of this method compared to TMS is that stimulation of cortical tissue could be highly localized as well as achieved at greater depths in the brain than is currently possible with TMS

Distortions of Subjective Time Perception Within and Across Senses

Background: The ability to estimate the passage of time is of fundamental importance for perceptual and cognitive processes. One experience of time is the perception of duration, which is not isomorphic to physical duration and can be distorted by a number of factors. Yet, the critical features generating these perceptual shifts in subjective duration are not understood. Methodology/Findings: We used prospective duration judgments within and across sensory modalities to examine the effect of stimulus predictability and feature change on the perception of duration. First, we found robust distortions of perceived duration in auditory, visual and auditory-visual presentations despite the predictability of the feature changes in the stimuli. For example, a looming disc embedded in a series of steady discs led to time dilation, whereas a steady disc embedded in a series of looming discs led to time compression. Second, we addressed whether visual (auditory) inputs could alter the perception of duration of auditory (visual) inputs. When participants were presented with incongruent audio-visual stimuli, the perceived duration of auditory events could be shortened or lengthened by the presence of conflicting visual information; however, the perceived duration of visual events was seldom distorted by the presence of auditory information and was never perceived shorter than their actual durations. Conclusions/Significance: These results support the existence of multisensory interactions in the perception of duration and, importantly, suggest that vision can modify auditory temporal perception in a pure timing task. Insofar as distortions in subjective duration can neither be accounted for by the unpredictability of an auditory, visual or auditory-visual event, we propose that it is the intrinsic features of the stimulus that critically affect subjective time distortions

Cost of hospitalization for childbirth in India: how equitable it is in the post-NRHM era?

BACKGROUND AND OBJECTIVE: Information on out-of-pocket (OOP) expenditure during childbirth in public and private health facilities in India is needed to make rational decisions for improving affordability to maternal care services. We undertook this study to evaluate the OOP expenditure due to hospitalization from childbirth and its impact on households. METHODS: This is a secondary data analysis of a nationwide household survey by the National Sample Survey Organization in 2014. The survey reported health service utilization and health care related expenditure by income quintiles and type of health facility. The recall period for hospitalization expenditure was 365 days. OOP expenditure amounting to more than 10% of annual consumption expenditure was termed as catastrophic. RESULTS: Median expenditure per episode of hospitalisation due to childbirth was US$54. The expenditure incurred was about six times higher among the richest quintile compared to the poorest quintile. Median private sector OOP hospitalization expenditure was nearly nine times higher than in the public sector. Hospitalization in a private sector facility leads to a significantly higher prevalence of catastrophic expenditure than hospitalization in a public sector (60% vs. 7%). Indirect cost (43%) constituted the largest share in the total expenditure in public sector hospitalizations. Urban residence, poor wealth quintile, residing in eastern and southern regions of India and delivery in private hospital were significantly associated with catastrophic expenditure. CONCLUSIONS: We strongly recommend cash transfer schemes with effective pro-poor targeting to reduce the impact of catastrophic expenditure. Strengthening of public health facilities is required along with private sector regulation

Transmembrane potential induced on the internal organelle by a time-varying magnetic field: a model study

<p>Abstract</p> <p>Background</p> <p>When a cell is exposed to a time-varying magnetic field, this leads to an induced voltage on the cytoplasmic membrane, as well as on the membranes of the internal organelles, such as mitochondria. These potential changes in the organelles could have a significant impact on their functionality. However, a quantitative analysis on the magnetically-induced membrane potential on the internal organelles has not been performed.</p> <p>Methods</p> <p>Using a two-shell model, we provided the first analytical solution for the transmembrane potential in the organelle membrane induced by a time-varying magnetic field. We then analyzed factors that impact on the polarization of the organelle, including the frequency of the magnetic field, the presence of the outer cytoplasmic membrane, and electrical and geometrical parameters of the cytoplasmic membrane and the organelle membrane.</p> <p>Results</p> <p>The amount of polarization in the organelle was less than its counterpart in the cytoplasmic membrane. This was largely due to the presence of the cell membrane, which "shielded" the internal organelle from excessive polarization by the field. Organelle polarization was largely dependent on the frequency of the magnetic field, and its polarization was not significant under the low frequency band used for transcranial magnetic stimulation (TMS). Both the properties of the cytoplasmic and the organelle membranes affect the polarization of the internal organelle in a frequency-dependent manner.</p> <p>Conclusions</p> <p>The work provided a theoretical framework and insights into factors affecting mitochondrial function under time-varying magnetic stimulation, and provided evidence that TMS does not affect normal mitochondrial functionality by altering its membrane potential.</p

Identification of Human IKK-2 Inhibitors of Natural Origin (Part I): Modeling of the IKK-2 Kinase Domain, Virtual Screening and Activity Assays

BACKGROUND: Their large scaffold diversity and properties, such as structural complexity and drug similarity, form the basis of claims that natural products are ideal starting points for drug design and development. Consequently, there has been great interest in determining whether such molecules show biological activity toward protein targets of pharmacological relevance. One target of particular interest is hIKK-2, a serine-threonine protein kinase belonging to the IKK complex that is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Indeed, this has led to the development of synthetic ATP-competitive inhibitors for hIKK-2. Therefore, the main goals of this study were (a) to use virtual screening to identify potential hIKK-2 inhibitors of natural origin that compete with ATP and (b) to evaluate the reliability of our virtual-screening protocol by experimentally testing the in vitro activity of selected natural-product hits. METHODOLOGY/PRINCIPAL FINDINGS: We thus predicted that 1,061 out of the 89,425 natural products present in the studied database would inhibit hIKK-2 with good ADMET properties. Notably, when these 1,061 molecules were merged with the 98 synthetic hIKK-2 inhibitors used in this study and the resulting set was classified into ten clusters according to chemical similarity, there were three clusters that contained only natural products. Five molecules from these three clusters (for which no anti-inflammatory activity has been previously described) were then selected for in vitro activity testing, in which three out of the five molecules were shown to inhibit hIKK-2. CONCLUSIONS/SIGNIFICANCE: We demonstrated that our virtual-screening protocol was successful in identifying lead compounds for developing new inhibitors for hIKK-2, a target of great interest in medicinal chemistry. Additionally, all the tools developed during the current study (i.e., the homology model for the hIKK-2 kinase domain and the pharmacophore) will be made available to interested readers upon request