Neural signatures of cognitive flexibility and reward sensitivity following nicotinic receptor stimulation in dependent smokers : a randomized trial

IMPORTANCE Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. OBJECTIVE To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. DESIGN, SETTING, AND PARTICIPANTS Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. MAIN OUTCOME AND MEASURES A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. RESULTS The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline. Similarly, decreased mesocorticolimbic activity associated with cognitive flexibility in abstinent smokers was restored to the level of nonsmokers following stimulation of nicotinic acetylcholine receptors (familywise error-corrected P<.05). Conversely, neural signatures of decreased reward sensitivity in smokers (vs nonsmokers; familywise error-corrected P<.05) in the dorsal striatum and anterior cingulate cortex were not mitigated by nicotine or varenicline. CONCLUSIONS AND RELEVANCE There was a double dissociation between the effects of chronic nicotine dependence on neural representations of reward sensitivity and acute effects of stimulation of nicotinic acetylcholine receptors on behavioral and neural signatures of cognitive flexibility in smokers. These chronic and acute pharmacologic effects were observed in overlapping mesocorticolimbic regions, suggesting that available pharmacotherapies may alleviate deficits in the same circuitry for certain mental computations but not for others

Non-Fermi-liquid behavior in Ce(Ru1−x_{1-x}Fex_x)2_2Ge2_2: cause and effect

We present inelastic neutron scattering measurements on the intermetallic compounds Ce(Ru$_{1-x}$Fe$_x$)$_2$Ge$_2$ ($x$=0.65, 0.76 and 0.87). These compounds represent samples in a magnetically ordered phase, at a quantum critical point and in the heavy-fermion phase, respectively. We show that at high temperatures the three compositions have the identical response of a local moment system. However, at low temperatures the spin fluctuations in the critical composition are given by non-Fermi-liquid dynamics, while the spin fluctuations in the heavy fermion system show a simple exponential decay in time. In both compositions, the lifetime of the fluctuations is determined solely by the distance to the quantum critical point. We discuss the implications of these observations regarding the possible origins of non-Fermi-liquid behavior in this system.Comment: 4 figures, submitted to PR

Effective Viscosity of Dilute Bacterial Suspensions: A Two-Dimensional Model

Suspensions of self-propelled particles are studied in the framework of two-dimensional (2D) Stokesean hydrodynamics. A formula is obtained for the effective viscosity of such suspensions in the limit of small concentrations. This formula includes the two terms that are found in the 2D version of Einstein's classical result for passive suspensions. To this, the main result of the paper is added, an additional term due to self-propulsion which depends on the physical and geometric properties of the active suspension. This term explains the experimental observation of a decrease in effective viscosity in active suspensions.Comment: 15 pages, 3 figures, submitted to Physical Biolog

On the Convergence of the Born Series in Optical Tomography with Diffuse Light

We provide a simple sufficient condition for convergence of Born series in the forward problem of optical diffusion tomography. The condition does not depend on the shape or spatial extent of the inhomogeneity but only on its amplitude.Comment: 23 pages, 7 figures, submitted to Inverse Problem

Spin glass behavior in URh_2Ge_2

URh_2Ge_2 occupies an extraordinary position among the heavy-electron 122-compounds, by exhibiting a previously unidentified form of magnetic correlations at low temperatures, instead of the usual antiferromagnetism. Here we present new results of ac and dc susceptibilities, specific heat and neutron diffraction on single-crystalline as-grown URh_2Ge_2. These data clearly indicate that crystallographic disorder on a local scale produces spin glass behavior in the sample. We therefore conclude that URh_2Ge_2 is a 3D Ising-like, random-bond, heavy-fermion spin glass.Comment: 10 pages, RevTeX, with 4 postscript figures, accepted by Physical Review Letters Nov 15, 199

Avalanche of Bifurcations and Hysteresis in a Model of Cellular Differentiation

Cellular differentiation in a developping organism is studied via a discrete bistable reaction-diffusion model. A system of undifferentiated cells is allowed to receive an inductive signal emenating from its environment. Depending on the form of the nonlinear reaction kinetics, this signal can trigger a series of bifurcations in the system. Differentiation starts at the surface where the signal is received, and cells change type up to a given distance, or under other conditions, the differentiation process propagates through the whole domain. When the signal diminishes hysteresis is observed