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

Boundary interactions changing operators and dynamical correlations in quantum impurity problems

Recent developments have made possible the computation of equilibrium dynamical correlators in quantum impurity problems. In many situations however, one is rather interested in correlators subject to a non equilibrium initial preparation; this is the case for instance for the occupation probability $P(t)$ in the double well problem of dissipative quantum mechanics (DQM). We show in this paper how to handle this situation in the framework of integrable quantum field theories by introducing ``boundary interactions changing operators''. We determine the properties of these operators by using an axiomatic approach similar in spirit to what is done for form-factors. This allows us to obtain new exact results for $P(t)$; for instance, we find that that at large times (or small $g$), the leading behaviour for g < 1/2} is $P(t)\propto e^{-\Gamma t}\cos\Omega t$, with the universal ratio. $\Omega/\Gamma = \cot {\pi g}/{2(1-g)}$.Comment: 4 pages, revte

The International Law of Discovery, Indigenous Peoples, and Chile

law in force at the time they were asserted.11 We hope that our effort will add to the work that has already been completed, and to that which is currently under way, to erase the Doctrine from international and national laws and to help reverse some of its pernicious effects on indigenous peoples. In Part II, we describe what the Doctrine of Discovery is, how it was developed in Europe, and how it was applied by Spain in the New World. Part III examines Chilean history and law to investigate whether Spanish and Chilean governments applied the Doctrine to the indigenous peoples that inhabited that region. We conclude in Part IV that Chile, just as all colonizing settler countries, must first recognize their use of the feudal, ethnocentric, racial, and religiously inspired international law of Discovery against indigenous peoples. Any attempt to redress past wrongs, and to create a more positive and equal future for all Chileans, must begin with recognition of this truth. From there, serious efforts should be made to eradicate the vestiges of Discovery from Chilean law and culture

Les ferments chlorophylliens

Lesage Jules. Les ferments chlorophylliens. In: Bulletin de l'Académie Vétérinaire de France tome 101 n°1, 1948. pp. 41-42

Form-factors computation of Friedel oscillations in Luttinger liquids

We show how to analytically determine for $g\leq 1/2$ the "Friedel oscillations" of charge density by a single impurity in a 1D Luttinger liquid of spinless electrons.Comment: Revtex, epsf, 4pgs, 2fig

Flow equation analysis of the anisotropic Kondo model

We use the new method of infinitesimal unitary transformations to calculate zero temperature correlation functions in the strong-coupling phase of the anisotropic Kondo model. We find the dynamics on all energy scales including the crossover behaviour from weak to strong coupling. The integrable structure of the Hamiltonian is not used in our approach. Our method should also be useful in other strong-coupling models since few other analytical methods allow the evaluation of their correlation functions on all energy scales.Comment: 4 pages RevTeX, 2 eps figures include