Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress

Currently approved repetitive transcranial magnetic stimulation (rTMS) protocols for the treatment of major depressive disorder (MDD) involve once-daily (weekday) stimulation sessions, with 10 Hz or intermittent theta burst stimulation (iTBS) frequencies, over 4–6 weeks. Recently, accelerated treatment protocols (multiple daily stimulation sessions for 1–2 weeks) have been increasingly studied to optimize rTMS treatments. Accelerated protocols might confer unique advantages for adolescents and young adults but there are many knowledge gaps related to dosing in this age group. Off-label, clinical practice frequently outpaces solid evidence as rigorous clinical trials require substantial time and resources. Murine models present an opportunity for high throughput dose finding studies to focus subsequent clinical trials in humans. This project investigated the brain and behavioural effects of an accelerated low-intensity rTMS (LI-rTMS) protocol in a young adult rodent model of chronic restraint stress (CRS). Depression and anxiety-related behaviours were induced in young adult male Sprague Dawley rats using the CRS model, followed by the 3-times-daily delivery of 10 Hz LI-rTMS, for two weeks. Behaviour was assessed using the Elevated Plus Maze and Forced Swim Test, and functional, chemical, and structural brain changes measured using magnetic resonance imaging techniques. CRS induced an agitated depression-like phenotype but therapeutic effects from the accelerated protocol were not detected. Our findings suggest that the age of rodents may impact response to CRS and LI-rTMS. Future studies should also examine higher intensities of rTMS and accelerated theta burst protocols

Validation of chronic restraint stress model in young adult rats for the study of depression using longitudinal multimodal MR imaging

Prior research suggests that the neurobiological underpinnings of depression include aberrant brain functional connectivity, neurometabolite levels, and hippocampal volume. Chronic restraint stress (CRS) depression model in rats has been shown to elicit behavioral, gene expression, protein, functional connectivity, and hippocampal volume changes similar to those in human depression. However, no study to date has examined the association between behavioral changes and brain changes within the same animals. This study specifically addressed the correlation between the outcomes of behavioral tests and multiple 9.4 T magnetic resonance imaging (MRI) modalities in the CRS model using data collected longitudinally in the same animals. CRS involved placing young adult male Sprague Dawley rats in individual transparent tubes for 2.5 h daily over 13 d. Elevated plus maze (EPM) and forced swim tests (FSTs) confirmed the presence of anxiety-like and depression-like behaviors, respectively, postrestraint. Resting-state functional MRI (rs-fMRI) data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. Proton magnetic resonance spectroscopy revealed decreased sensorimotor cortical glutamate (Glu), glutamine (Gln), and combined Glu-Gln (Glx) levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume. Importantly, these changes parallel those found in human depression, suggesting that the CRS rodent model has utility for translational studies and novel intervention development for depression

White matter changes following chronic restraint stress and neuromodulation: A diffusion magnetic resonance imaging study in young male rats

Background Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation technique, is an effective treatment for depression. However, few studies have used diffusion magnetic resonance imaging to investigate the longitudinal effects of rTMS on the abnormal brain white matter (WM) described in depression. Methods In this study, we acquired diffusion magnetic resonance imaging from young adult male Sprague Dawley rats to investigate 1) the longitudinal effects of 10- and 1-Hz low-intensity rTMS (LI-rTMS) in healthy animals; 2) the effect of chronic restraint stress (CRS), an animal model of depression; and 3) the effect of 10 Hz LI-rTMS in CRS animals. Diffusion magnetic resonance imaging data were analyzed using tract-based spatial statistics and fixel-based analysis. Results Similar changes in diffusion and kurtosis fractional anisotropy were induced by 10- and 1-Hz stimulation in healthy animals, although changes induced by 10-Hz stimulation were detected earlier than those following 1-Hz stimulation. Additionally, 10-Hz stimulation increased axial and mean kurtosis within the external capsule, suggesting that the two protocols may act via different underlying mechanisms. Brain maturation–related changes in WM, such as increased corpus callosum, fimbria, and external and internal capsule fiber cross-section, were compromised in CRS animals compared with healthy control animals and were rescued by 10-Hz LI-rTMS. Immunohistochemistry revealed increased myelination within the corpus callosum in LI-rTMS–treated CRS animals compared with those that received sham or no stimulation. Conclusions Overall, decreased WM connectivity and integrity in the CRS model corroborate findings in patients experiencing depression with high anxiety, and the observed LI-rTMS–induced effects on WM structure suggest that LI-rTMS might rescue abnormal WM by increasing myelination

Heavy quarkonium 2S states in light-front quark model

We study the charmonium 2S states $\psi'$ and $\eta_c'$, and the bottomonium 2S states $\Upsilon'$ and $\eta_b'$, using the light-front quark model and the 2S state wave function of harmonic oscillator as the approximation of the 2S quarkonium wave function. The decay constants, transition form factors and masses of these mesons are calculated and compared with experimental data. Predictions of quantities such as Br$(\psi' \to \gamma \eta_c')$ are made. The 2S wave function may help us learn more about the structure of these heavy quarkonia.Comment: 5 latex pages, final version for journal publicatio

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays

A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity

Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays

Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of prime importance in probing new physics. Here 7421 +/- 105 signal events from the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A time-dependent fit to the data yields a value of phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201

Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds