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Theories of decision-making and its neural substrates have long assumed the existence of two distinct and competing valuation systems, variously described as goal-directed vs. habitual, or, more recently and based on statistical arguments, as model-free vs. model-based reinforcement-learning. Though both have been shown to control choices, the cognitive abilities associated with these systems are under ongoing investigation. Here we examine the link to cognitive abilities, and find that individual differences in processing speed covary with a shift from model-free to model-based choice control in the presence of above-average working memory function. This suggests shared cognitive and neural processes; provides a bridge between literatures on intelligence and valuation; and may guide the development of process models of different valuation components. Furthermore, it provides a rationale for individual differences in the tendency to deploy valuation systems, which may be important for understanding the manifold neuropsychiatric diseases associated with malfunctions of valuation.
Background Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. Methods To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Results Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Conclusion Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.
Gamma-ray line signatures can be expected in the very-high-energy (E-gamma > 100 GeV) domain due to self-annihilation or decay of dark matter (DM) particles in space. Such a signal would be readily distinguishable from astrophysical gamma-ray sources that in most cases produce continuous spectra that span over several orders of magnitude in energy. Using data collected with the H. E. S. S. gamma-ray instrument, upper limits on linelike emission are obtained in the energy range between similar to 500 GeV and similar to 25 TeV for the central part of the Milky Way halo and for extragalactic observations, complementing recent limits obtained with the Fermi-LAT instrument at lower energies. No statistically significant signal could be found. For monochromatic gamma-ray line emission, flux limits of (2 x 10(-7)-2 x 10(-5)) m(-2)s(-1)sr(-1) and (1 x 10(-8)- 2 x 10(-6)) m(-2)s(-1)sr(-1) are obtained for the central part of the Milky Way halo and extragalactic observations, respectively. For a DM particle mass of 1 TeV, limits on the velocity- averaged DM annihilation cross section <sigma upsilon >(chi chi ->gamma gamma) reach similar to 10(-27)cm(3)s(-1), based on the Einasto parametrization of the Galactic DM halo density profile. DOI: 10.1103/PhysRevLett.110.041301
Context. Globular clusters (GCs) are established emitters of high-energy (HE, 100 MeV < E < 100 GeV) gamma-ray radiation which could originate from the cumulative emission of the numerous millisecond pulsars (msPSRs) in the clusters’ cores or from inverse Compton (IC) scattering of relativistic leptons accelerated in the GC environment. These stellar clusters could also constitute a new class of sources in the very-high-energy (VHE, E > 100 GeV) gamma-ray regime, judging from the recent detection of a signal from the direction of Terzan 5 with the H.E.S.S. telescope array. Aims. To search for VHE gamma-ray sources associated with other GCs, and to put constraints on leptonic emission models, we systematically analyzed the observations towards 15 GCs taken with the H. E. S. S. array of imaging atmospheric Cherenkov telescopes. Methods. We searched for point-like and extended VHE gamma-ray emission from each GC in our sample and also performed a stacking analysis combining the data from all GCs to investigate the hypothesis of a population of faint emitters. Assuming IC emission as the origin of the VHE gamma-ray signal from the direction of Terzan 5, we calculated the expected gamma-ray flux from each of the 15 GCs, based on their number of millisecond pulsars, their optical brightness and the energy density of background photon fields. Results. We did not detect significant VHE gamma-ray emission from any of the 15 GCs in either of the two analyses. Given the uncertainties related to the parameter determinations, the obtained flux upper limits allow to rule out the simple IC/msPSR scaling model for NGC6388 and NGC7078. The upper limits derived from the stacking analyses are factors between 2 and 50 below the flux predicted by the simple leptonic scaling model, depending on the assumed source extent and the dominant target photon fields. Therefore, Terzan 5 still remains exceptional among all GCs, as the VHE gamma-ray emission either arises from extra-ordinarily efficient leptonic processes, or from a recent catastrophic event, or is even unrelated to the GC itself.
Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
We used single-molecule FRET in combination with other biophysical methods and molecular simulations to investigate the effect of temperature on the dimensions of unfolded proteins. With singlemolecule FRET, this question can be addressed even under nearnative conditions, where most molecules are folded, allowing us to probe a wide range of denaturant concentrations and temperatures. We find a compaction of the unfolded state of a small cold shock protein with increasing temperature in both the presence and the absence of denaturant, with good agreement between the results from single-molecule FRET and dynamic light scattering. Although dissociation of denaturant from the polypeptide chain with increasing temperature accounts for part of the compaction, the results indicate an important role for additional temperaturedependent interactions within the unfolded chain. The observation of a collapse of a similar extent in the extremely hydrophilic, intrinsically disordered protein prothymosin suggests that the hydrophobic effect is not the sole source of the underlying interactions. Circular dichroism spectroscopy and replica exchange molecular dynamics simulations in explicit water show changes in secondary structure content with increasing temperature and suggest a contribution of intramolecular hydrogen bonding to unfolded state collapse.
Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction.
Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol-dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol-dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol.