Variability in cTBS Aftereffects Attributed to the Interaction of Stimulus Intensity With BDNF Val66Met Polymorphism

Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity.Methods: Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI.Results: For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration.Conclusions: cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects.Significance: These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Simultaneous RP-HPLC and UV Spectroscopic Method Development and Validation for Estimation of Ibandronate Sodium in Bulk and Pharmaceutical Dosage Form

The present study describes a simple, accurate, precise and cost effective UV-Vis Spectroscopic and RP-HPLC method for the estimation of Ibandronate sodium (IBN). The determination of Ibandronate sodium (IBN) was performed by both UV and RP-HPLC method using 215 nm as the determination wavelength. The drug was dissolved in NaOH solution (0.1N NaOH) for estimation in UV and in distilled water for the estimation in RP-HPLC using mobile phase 0.01 M Sodium dihydrogen phosphate (NaH2PO4): Acetonitrile (80:20), pH being adjusted to 3.3 with 10% ortho-phosphoric acid. A linear response was observed in the range of 10-50 μg ml-1 (R2 = 0.9981) for UV-Spectroscopy, whereas for RP-HPLC the linear response was observed in the range of 20-70 μg ml-1 (R2 = 0.9965). The limits of quantitation (LOQ) were estimated as 0.1 μg ml-1 and 0.05 μg ml-1, respectively for UV and RP-HPLC respectively. The recoveries of IBN from the marketed formulation were found to be within 100 ± 2% by both the methods. These methods were then effectively applied for the estimation of Boniva (tablet) and the results were obtained according to nominal content. The statistical analysis revealed that there is no significant difference (p > 0.05) between UV and HPLC methods regarding validation parameters and assay content

Concussion Alters the Functional Brain Processes of Visual Attention and Working Memory.

Millions of North Americans sustain a concussion or a mild traumatic brain injury annually, and are at risk of cognitive, emotional, and physical sequelae. Although functional MRI (fMRI) studies have provided an initial framework for examining functional deficits induced by concussion, particularly working memory and attention, the temporal dynamics underlying these deficits are not well understood. We used magnetoencephalography (MEG), a modality with millisecond temporal resolution, in conjunction with a 1-back visual working memory (VWM) paradigm using scenes from everyday life to characterize spatiotemporal functional differences at specific VWM stages, in adults had had or had not had a recent concussion. MEG source-level differences between groups were determined by whole-brain analyses during encoding and recognition phases. Despite comparable behavioral performance, abnormal hypo- and hyperactivation patterns were found in brain areas involving frontoparietal, ventral occipitotemporal, temporal, and subcortical areas in concussed patients. These patterns and their timing varied as a function of VWM stagewise processing, linked to early attentional control, visuoperceptual scene processing, and VWM maintenance and retrieval processes. Parietal hypoactivation, starting at 60 ms during encoding, was correlated with symptom severity, possibly linked to impaired top-down attentional processing. Hyperactivation in the scene-selective occipitotemporal areas, the medial temporal complex, specifically the right hippocampus and orbitofrontal areas during encoding and/or recognition, lead us to posit inefficient but compensatory visuoperceptual, relational, and retrieval processing. Although injuries sustained after the concussion were considered "mild," these data suggest that they can have prolonged effects on early attentional and VWM processes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Gamma Amplitude-Envelope Correlations Are Strongly Elevated within Hyperexcitable Networks in Focal Epilepsy

Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40–200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas. To test this prediction, we analyzed archived samples of interictal electrocorticographic (ECoG) signals recorded from patients who became seizure-free after surgery targeting SOZs identified by multiday intracranial recordings. We show that in the gamma band, AECs between nodes within SOZs are markedly elevated relative to those elsewhere. AEC-based node strength, eigencentrality, and clustering coefficient are also robustly increased within the SOZ with maxima in the low-gamma band (permutation test Z-scores \u3e 8) and yield moderate discriminability of the SOZ using ROC analysis (maximal mean AUC ~ 0.73). By contrast to AECs, phase locking values (PLVs), a measure of narrow-band phase coupling across sites, and PLV-based graph metrics discriminate the seizure onset nodes weakly. Our results suggest that gamma band AECs may provide a clinically useful marker of cortical hyperexcitability in focal epilepsy

Data_Sheet_1_Visual Working Memory Encoding and Recognition in Good Outcome Aneurysmal Subarachnoid Patients.DOCX

<p>Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) accounts for less than 5% of strokes but is associated with significant morbidity and mortality. Amongst survivors, neurocognitive complaints are common, often despite normal imaging. We used magnetoencephalography (MEG) to investigate neurophysiological function during a visual working memory task in aSAH survivors with good recovery and normal structural imaging.</p><p>Methods: Patients with aSAH treated with coiling and exhibiting good outcome measured by Glasgow Outcome Scale (GOS) and without related parenchymal structural lesions in post-treatment MRI, were recruited and compared to age- and sex-matched controls. All participants underwent intelligence and cognitive screening, structural MRI, and MEG testing in conjunction with a 1-back visual working memory task. Sensor-level global field power and virtual electrode source analysis of neuronal activity and connectivity in aSAH were assessed.</p><p>Results: Thirteen patients and 13 matched controls were enrolled (age: 56 ± 11 years, 19 female). The 1-back task was completed with similar accuracy despite a trend for a longer reaction time in aSAH patients (p = 0.054). During encoding and recognition phases, aSAH patients showed significantly increased neuronal activation and hyperconnectivity in periventricular areas, specifically the anterior and posterior cingulate gyri.</p><p>Conclusions: Increased posterior and anterior cingulate gyri neuronal activity is demonstrated in aSAH patients during visual working memory tasks, in the absence of structural lesions. These areas work mainly as a hub to “organize” memory storage and retrieval. Increased activity in these areas might be compensatory due to injury and consequently loss of neuronal response in connected areas in the working memory networks.</p