The basal ganglia in perceptual timing: timing performance in Multiple System Atrophy and Huntington's disease.

The timing of perceptual events depends on an anatomically and functionally connected network comprising basal ganglia, cerebellum, pre-frontal cortex and supplementary motor area. Recent studies demonstrate the cerebellum to be involved in absolute, duration-based timing, but not in relative timing based on a regular beat. Conversely, functional involvement of the striatum is observed in relative timing, but its role in absolute timing is unclear. This work tests the specific role of the basal ganglia in the perceptual timing of auditory events. It aims to distinguish the hypothesised unified model of time perception (Teki, Grube, & Griffiths, 2012), in which the striatum is a mandatory component for all timing tasks, from a modular system in which they subserve relative timing, with absolute timing processed by the cerebellum. Test groups comprised individuals with Multiple System Atrophy, a disorder in which similar pathology can produce clinical deficits associated with dysfunction of the cerebellum (MSA-C, n = 8) or striatum (MSA-P, n = 10), and early symptomatic Huntington's disease (HD, n = 14). Individuals with chronic autoimmune peripheral neuropathy (n = 11) acted as controls. Six adaptive tasks were carried out to assess perceptual thresholds for absolute timing through duration discrimination for sub- and supra-second time intervals, and relative timing through the detection of beat-based regularity and irregularity, detection of a delay within an isochronous sequence, and the discrimination of sequences with metrical structure. All three patient groups exhibited impairments in performance in comparison with the control group for all tasks, and severity of impairment was significantly correlated with disease progression. No differences were demonstrated between MSA-C and MSA-P, and the most severe impairments were observed in those with HD. The data support an obligatory role for the basal ganglia in all tested timing tasks, both absolute and relative, as predicted by the unified model. The results are not compatible with models of a brain timing network based upon independent modules

Subthalamic deep brain stimulation in Parkinson׳s disease has no significant effect on perceptual timing in the hundreds of milliseconds range.

Bilateral, high-frequency stimulation of the basal ganglia (STN-DBS) is in widespread use for the treatment of the motor symptoms of Parkinson׳s disease (PD). We present here the first psychophysical investigation of the effect of STN-DBS upon perceptual timing in the hundreds of milliseconds range, with both duration-based (absolute) and beat-based (relative) tasks; 13 patients with PD were assessed with their STN-DBS 'on', 'off', and then 'on' again. Paired parametric analyses revealed no statistically significant differences for any task according to DBS status. We demonstrate, from the examination of confidence intervals, that any functionally relevant effect of STN-DBS on relative perceptual timing is statistically unlikely. For absolute, duration-based timing, we demonstrate that the activation of STN-DBS may either worsen performance or have no effect, but that it is unlikely to lead to significant improvement. Although these results are negative they have important implications for our understanding of perceptual timing and its relationship to motor functions within the timing network of the brain. They imply that the mechanisms involved in the perceptual processing of temporal information are likely to be functionally independent from those that underpin movement. Further, they suggest that the connections between STN and the subtantia nigra and globus pallidus are unlikely to be critical to beat-based perceptual timing

Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial

BACKGROUND: Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. METHODS: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. RESULTS: Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. CONCLUSIONS: This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy

Detecting Selection in the HIV-1 Genome during Sexual Transmission Events

Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population. We analyzed 30 transmitter-recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes. We developed a new statistical test to detect selection during transmission, called Selection Test in Transmission (SeTesT), based on comparing the transmitter and recipient virus population and accounting for the transmission bottleneck. We performed extensive simulations and found that sensitivity of detecting selection during transmission is limited by the strong population bottleneck of few transmitted virions. When pooling individual test results across patients, we found two candidate HIV-1 genomic features for affecting transmission, namely amino acid positions 3 and 18 of Vpu, which were significant before but not after correction for multiple testing. In summary, SeTesT provides a general framework for detecting selection based on genomic sequencing data of transmitted viruses. Our study shows that a higher number of transmitter-recipient pairs is required to improve sensitivity of detecting selection

Longitudinal Spin Transfer to Λ\Lambda and Λˉ\bar{\Lambda} Hyperons in Polarized Proton-Proton Collisions at s\sqrt{s} = 200 GeV

The longitudinal spin transfer, $D_{LL}$, from high energy polarized protons to $\Lambda$ and $\bar{\Lambda}$ hyperons has been measured for the first time in proton-proton collisions at $\sqrt{s} = 200 \mathrm{GeV}$ with the STAR detector at RHIC. The measurements cover pseudorapidity, $\eta$, in the range $|\eta| < 1.2$ and transverse momenta, $p_\mathrm{T}$, up to $4 \mathrm{GeV}/c$. The longitudinal spin transfer is found to be $D_{LL}= -0.03\pm 0.13(\mathrm{stat}) \pm 0.04(\mathrm{syst})$ for inclusive $\Lambda$ and $D_{LL} = -0.12 \pm 0.08(\mathrm{stat}) \pm 0.03(\mathrm{syst})$ for inclusive $\bar{\Lambda}$ hyperons with $= 0.5$ and $= 3.7 \mathrm{GeV}/c$. The dependence on $\eta$ and $p_\mathrm{T}$ is presented.Comment: 5 pages, 4 figure

Longitudinal double-spin asymmetry for inclusive jet production in p+p collisions at sqrt(s)=200 GeV

We report a new STAR measurement of the longitudinal double-spin asymmetry A_LL for inclusive jet production at mid-rapidity in polarized p+p collisions at a center-of-mass energy of sqrt(s) = 200 GeV. The data, which cover jet transverse momenta 5 < p_T < 30 GeV/c, are substantially more precise than previous measurements. They provide significant new constraints on the gluon spin contribution to the nucleon spin through the comparison to predictions derived from one global fit of polarized deep-inelastic scattering measurements.Comment: 7 pages, 4 figures + 1 tabl

Measurements of ϕ\phi meson production in relativistic heavy-ion collisions at RHIC

We present results for the measurement of $\phi$ meson production via its charged kaon decay channel $\phi \to K^+K^-$ in Au+Au collisions at $\sqrt{s_{_{NN}}}=62.4$, 130, and 200 GeV, and in $p+p$ and $d$+Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV from the STAR experiment at the BNL Relativistic Heavy Ion Collider (RHIC). The midrapidity ($|y|<0.5$) $\phi$ meson transverse momentum ($p_{T}$) spectra in central Au+Au collisions are found to be well described by a single exponential distribution. On the other hand, the $p_{T}$ spectra from $p+p$, $d$+Au and peripheral Au+Au collisions show power-law tails at intermediate and high $p_{T}$ and are described better by Levy distributions. The constant $\phi/K^-$ yield ratio vs beam species, collision centrality and colliding energy is in contradiction with expectations from models having kaon coalescence as the dominant mechanism for $\phi$ production at RHIC. The $\Omega/\phi$ yield ratio as a function of $p_{T}$ is consistent with a model based on the recombination of thermal $s$ quarks up to $p_{T}\sim 4$ GeV/$c$, but disagrees at higher transverse momenta. The measured nuclear modification factor, $R_{dAu}$, for the $\phi$ meson increases above unity at intermediate $p_{T}$, similar to that for pions and protons, while $R_{AA}$ is suppressed due to the energy loss effect in central Au+Au collisions. Number of constituent quark scaling of both $R_{cp}$ and $v_{2}$ for the $\phi$ meson with respect to other hadrons in Au+Au collisions at $\sqrt{s_{_{NN}}}$=200 GeV at intermediate $p_{T}$ is observed. These observations support quark coalescence as being the dominant mechanism of hadronization in the intermediate $p_{T}$ region at RHIC.Comment: 22 pages, 21 figures, 4 table

Spin alignment measurements of the K∗0(892)K^{*0}(892) and ϕ(1020)\phi(1020) vector mesons at RHIC

We present the first spin alignment measurements for the $K^{*0}(892)$ and $\phi(1020)$ vector mesons produced at mid-rapidity with transverse momenta up to 5 GeV/c at $\sqrt{s_{NN}}$ = 200 GeV at RHIC. The diagonal spin density matrix elements with respect to the reaction plane in Au+Au collisions are $\rho_{00}$ = 0.32 $\pm$ 0.04 (stat) $\pm$ 0.09 (syst) for the $K^{*0}$ ($0.8<p_T<5.0$ GeV/c) and $\rho_{00}$ = 0.34 $\pm$ 0.02 (stat) $\pm$ 0.03 (syst) for the $\phi$ ($0.4<p_T<5.0$ GeV/c), and are constant with transverse momentum and collision centrality. The data are consistent with the unpolarized expectation of 1/3 and thus no evidence is found for the transfer of the orbital angular momentum of the colliding system to the vector meson spins. Spin alignments for $K^{*0}$ and $\phi$ in Au+Au collisions were also measured with respect to the particle's production plane. The $\phi$ result, $\rho_{00}$ = 0.41 $\pm$ 0.02 (stat) $\pm$ 0.04 (syst), is consistent with that in p+p collisions, $\rho_{00}$ = 0.39 $\pm$ 0.03 (stat) $\pm$ 0.06 (syst), also measured in this work. The measurements thus constrain the possible size of polarization phenomena in the production dynamics of vector mesons.Comment: 7 pages, 4 figures. fig.1 updated; one more reference added, one typo corrected, published in PRC.77.06190

System-Size Independence of Directed Flow Measured at the BNL Relativistic Heavy-Ion Collider

We measure directed flow (ν_1) for charged particles in Au+Au and Cu+Cu collisions at √S_(NN)=200 and 62.4 GeV, as a function of pseudorapidity (η), transverse momentum (p_t), and collision centrality, based on data from the STAR experiment. We find that the directed flow depends on the incident energy but, contrary to all available model implementations, not on the size of the colliding system at a given centrality. We extend the validity of the limiting fragmentation concept to ν_1 in different collision systems, and investigate possible explanations for the observed sign change in ν_1(p_t)

Enhanced strange baryon production in Au+Au collisions compared to p+p at sqrts = 200 GeV

We report on the observed differences in production rates of strange and multi-strange baryons in Au+Au collisions at sqrts = 200 GeV compared to pp interactions at the same energy. The strange baryon yields in Au+Au collisions, then scaled down by the number of participating nucleons, are enhanced relative to those measured in pp reactions. The enhancement observed increases with the strangeness content of the baryon, and increases for all strange baryons with collision centrality. The enhancement is qualitatively similar to that observed at lower collision energy sqrts =17.3 GeV. The previous observations are for the bulk production, while at intermediate pT, 1 < pT< 4 GeV/c, the strange baryons even exceed binary scaling from pp yields.Comment: 7 pages, 4 figures. Printed in PR