Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users.

Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1- and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPnd) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPnd. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPnd was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPnd for either dopamine receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use.

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

OBJECTIVE: To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). MATERIALS AND METHODS: We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. RESULTS: We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). CONCLUSIONS: There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.

Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: link to impulsivity in methamphetamine users.

Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between the midbrain and striatum, orbitofrontal cortex and insula in methamphetamine-dependent participants, but a positive relationship in the control group. In Study 2, an interaction of the group with RSFC on impulsivity was observed. Methamphetamine-dependent users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect the system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals.

Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P<0.05 corrected for multiple comparisons). Craving for methamphetamine was negatively associated with gray-matter volume in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus (P<0.05 corrected for multiple comparisons). A relationship between midbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders.

Study of CP asymmetry in B

We present a measurement of the asymmetry A_{CP} between same-sign inclusive dilepton samples ℓ^{+}ℓ^{+} and ℓ^{-}ℓ^{-} (ℓ=e, µ) from semileptonic B decays in ϒ(4S)→BB[over ¯] events, using the complete data set recorded by the BABAR experiment near the ϒ(4S) resonance, corresponding to 471×10^{6} BB[over ¯] pairs. The asymmetry A_{CP} allows comparison between the mixing probabilities P(B[over ¯]^{0}→B^{0}) and P(B^{0}→B[over ¯]^{0}), and therefore probes CP and T violation. The result, A_{CP}=[-3.9±3.5(stat)±1.9(syst)]×10^{-3}, is consistent with the standard model expectation.

Search for a dark photon in e(+)e(-) collisions at BABAR.

Dark sectors charged under a new Abelian interaction have recently received much attention in the context of dark matter models. These models introduce a light new mediator, the so-called dark photon (A^{'}), connecting the dark sector to the standard model. We present a search for a dark photon in the reaction e^{+}e^{-}→γA^{'}, A^{'}→e^{+}e^{-}, µ^{+}µ^{-} using 514 fb^{-1} of data collected with the BABAR detector. We observe no statistically significant deviations from the standard model predictions, and we set 90% confidence level upper limits on the mixing strength between the photon and dark photon at the level of 10^{-4}-10^{-3} for dark photon masses in the range 0.02-10.2 GeV. We further constrain the range of the parameter space favored by interpretations of the discrepancy between the calculated and measured anomalous magnetic moment of the muon.

Measurement of the D*(2010)+ meson width and the D*(2010)+ - D0 mass difference.

We measure the mass difference Δm0 between the D*(2010)+ and the D0 and the natural linewidth Γ of the transition D*(2010)+ → D0π+. The data were recorded with the BABAR detector at center-of-mass energies at and near the Υ(4S) resonance, and correspond to an integrated luminosity of approximately 477 fb(-1). The D0 is reconstructed in the decay modes D0 → K- π+ and D0 → K- π+ π- π+. For the decay mode D0 → K- π+ we obtain Γ = (83.4±1.7±1.5) keV and Δm0 = (145425.6±0.6±1.7) keV, [corrected] where the quoted errors are statistical and systematic, respectively. For the D0 → K- π+ π- π+ mode we obtain Γ = (83.2±1.5±2.6) keV and Δm0 = (145426.6±0.5±1.9) keV. [corrected] The combined measurements yield Γ = (83.3±1.2±1.4) keV and Δm0 = (145425.9±0.4±1.7) keV; the width is a factor of approximately 12 times more precise than the previous value, while the mass difference is a factor of approximately 6 times more precise.

Search for CP violation in B0-B0 mixing using partial reconstruction of B0→D*- Xℓ+ νℓ and a kaon tag.

We present results of a search for CP violation in B0- B0 mixing with the BABAR detector. We select a sample of B0→D*- Xℓ+ ν decays with a partial reconstruction method and use kaon tagging to assess the flavor of the other B meson in the event. We determine the CP violating asymmetry ACP≡[N(B0B0)-N(B0B0)]/[N(B0B0)+N(B0B0)]=(0.06±0.17(-0.32)(+0.38))%, corresponding to ΔCP=1-|q/p|=(0.29±0.84(-1.61)(+1.88))×10(-3).

Precision measurement of the B → Xs γ photon energy spectrum, branching fraction, and direct CP asymmetry A(CP)((B → X(s+d)γ).

The photon spectrum in the inclusive electromagnetic radiative decays of the B meson, B → X(s)γ plus B → X(d)γ, is studied using a data sample of (382.8 ± 4.2) × 10(6)Υ(4S) → BB decays collected by the BABAR experiment at SLAC. The spectrum is used to extract the branching fraction B(B → X(s)γ) = (3.21 ± 0.33) × 10(-4) for E(γ) >1.8 GeV and the direct CP asymmetry A(CP) (B → X(s+d)γ) = 0.057 ± 0.063. The effects of detector resolution and Doppler smearing are unfolded to measure the photon energy spectrum in the B meson rest frame.

Observation of time-reversal violation in the B0 meson system.

Although CP violation in the B meson system has been well established by the B factories, there has been no direct observation of time-reversal violation. The decays of entangled neutral B mesons into definite flavor states (B(0) or B(0)), and J/ψK(L)(0) or ccK(S)(0) final states (referred to as B(+) or B(-)), allow comparisons between the probabilities of four pairs of T-conjugated transitions, for example, B(0) → B(-) and B(-) → B(0), as a function of the time difference between the two B decays. Using 468 × 10(6) BB pairs produced in Υ(4S) decays collected by the BABAR detector at SLAC, we measure T-violating parameters in the time evolution of neutral B mesons, yielding ΔS(T)(+) = -1.37 ± 0.14(stat) ± 0.06(syst) and ΔS(T)(-) = 1.17 ± 0.18(stat) ± 0.11(syst). These nonzero results represent the first direct observation of T violation through the exchange of initial and final states in transitions that can only be connected by a T-symmetry transformation.

Evidence for an excess of B→D*τ(-)ν(τ) decays.

Based on the full BABAR data sample, we report improved measurements of the ratios R(D(*))=B(B[over ¯]→D(*)τ(-)ν[over ¯](τ))/B(B[over ¯]→D(*)ℓ(ℓ)(-)ν[over ¯](ℓ)), where ℓ is either e or µ. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D)=0.440±0.058±0.042 and R(D(*))=0.332±0.024±0.018, which exceed the standard model expectations by 2.0σ and 2.7σ, respectively. Taken together, our results disagree with these expectations at the 3.4σ level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model.

Search for low-mass dark-sector Higgs bosons.

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb(-1) of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the standard model-dark-sector mixing angle and the dark-sector coupling constant.

Search for hadronic decays of a light Higgs boson in the radiative decay Υ→γA0.

We search for hadronic decays of a light Higgs boson (A(0)) produced in radiative decays of an Υ(2S) or Υ(3S) meson, Υ→γA(0). The data have been recorded by the BABAR experiment at the Υ(3S) and Υ(2S) center-of-mass energies and include (121.3±1.2)×10(6) Υ(3S) and (98.3±0.9)×10(6) Υ(2S) mesons. No significant signal is observed. We set 90% confidence level upper limits on the product branching fractions B(Υ(nS)→γA(0))B(A(0)→hadrons) (n=2 or 3) that range from 1×10(-6) for an A(0) mass of 0.3 GeV/c(2) to 8×10(-5) at 7 GeV/c(2).

Observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ).

We report the observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) based on 342 fb(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e+ e- storage rings at SLAC. A simultaneous fit to three D(s)(+) decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B- → D(s)((*)+) K- ℓ- ν(ℓ)) = [6.13(-1.03)(+1.04)(stat)±0.43(syst)±0.51(B(D(s)))]×10(-4), where the last error reflects the limited knowledge of the D(s) branching fractions.

Search for production of invisible final states in single-photon decays of Υ(1S).

We search for single-photon decays of the Υ(1S) resonance, Υ â†’ γ + invisible, where the invisible state is either a particle of definite mass, such as a light Higgs boson A°, or a pair of dark matter particles, χχ. Both A° and χ are assumed to have zero spin. We tag Υ(1S) decays with a dipion transition Υ(2S) → π⁺π⁻Υ(1S) and look for events with a single energetic photon and significant missing energy. We find no evidence for such processes in the mass range m(A°) ≤ 9.2 GeV and m(χ) ≤ 4.5 GeV in the sample of 98 × 106 Υ(2S) decays collected with the BABAR detector and set stringent limits on new physics models that contain light dark matter states.

Test of lepton universality in Υ(1S) decays at BABAR.

The ratio R(τµ)(Υ(1S))=Γ(Υ(1S)→τ+ τ-)/Γ(Υ(1S)→µ+ µ-) is measured using a sample of (121.8±1.2)×10(6)Υ(3S) events recorded by the BABAR detector. This measurement is intended as a test of lepton universality and as a search for a possible light pseudoscalar Higgs boson. In the standard model (SM) this ratio is expected to be close to 1. Any significant deviations would violate lepton universality and could be introduced by the coupling to a light pseudoscalar Higgs boson. The analysis studies the decays Υ(3S)→Υ(1S)π+ π-, Υ(1S)→l+ l-, where l=µ, τ. The result, R(τµ)(Υ(1S))=1.005±0.013(stat)±0.022(syst), shows no deviation from the expected SM value, while improving the precision with respect to previous measurements.

Evidence for direct CP violation in the measurement of the Cabbibo-Kobayashi-Maskawa angle γ with B∓ → D(*)K(*)∓ decays.

We report the measurement of the Cabibbo-Kobayashi-Maskawa CP-violating angle γ through a Dalitz plot analysis of neutral D-meson decays to K(S)(0) π+ π- and K(S)(0) K+ K- produced in the processes B∓ → DK∓, B∓ D* K∓ with D* → Dπ(0), Dγ, and B∓ → DK*∓ with K*∓ → K(S)(0) π∓, using 468 million BB pairs collected by the BABAR detector at the PEP-II asymmetric-energy e+ e- collider at SLAC. We measure γ = (68 ± 14 ± 4 ± 3)° (modulo 180°), where the first error is statistical, the second is the experimental systematic uncertainty, and the third reflects the uncertainty in the description of the neutral D decay amplitudes. This result is inconsistent with γ = 0 (no direct CP violation) with a significance of 3.5 standard deviations.