In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Eddy-current (EC) and motion effects in diffusion-tensor imaging (DTI) bias the estimation of quantitative diffusion indices, such as the fractional anisotropy. Both effects can be retrospectively corrected by registering the strongly distorted diffusion-weighted images to less-distorted T2-weighted images acquired without diffusion weighting. Two different affine spatial transformations are usually employed for this correction: slicewise and whole-brain transformations. However, a relation between estimated transformation parameters and EC distortions has not been established yet for the latter approach. In this study, a novel diffusion-gradient-direction-independent estimation of the EC field is proposed based solely on affine whole-brain registration parameters. Using this model, it is demonstrated that a more distinct evaluation of the wholebrain EC effects is possible if the through-plane distortion was considered in addition to the well-known in-plane distortions. Moreover, a comparison of different whole-brain registrations relative to a slicewise approach is performed, in terms of the relative tensor error. Our findings suggest that for appropriate intersubject comparison of DTI data, a whole-brain registration containing nine affine parameters provides comparable performance (between 0 and 3%) to slicewise methods and can be performed in a fraction of the time.Magn strong gradients used for diffusion encoding (in the following referred to as "diffusion gradients") create ECs in the conductive parts of the magnet, causing geometric distortions in the DW images that depend on the amplitude and direction of the diffusion gradients (11-14). The EC effects depend on the pulse sequence (15-18), scanner calibration, and scanner design. The EC and motion effects can be retrospectively corrected by registering the strongly distorted DW images to the less distorted images acquired without diffusion weighting (14,19). However, the EC effects cannot be completely corrected by retrospective registration. Thus, after retrospective EC correction residual image artifacts (e.g., image blurring caused by the time-dependent components of the EC field) will remain and reduce the comparability of DTI data. This is particularly important for longitudinal DTI studies, during which the scanner adjustment and, thus, the EC effects might vary.One possibility for assessing the comparability of DTI data is to quantify EC effects by estimating the induced EC field. Rohde et al. (20) presented a new registration approach for EC and motion correction, using a whole-brain transformation. They showed that the EC field induced by one diffusion gradient can be retrospectively estimated from the transformation parameters of a 14-parameter, nonlinear transformation that corrects the distortions of the corresponding DW image. The DTI data, however, consists of at least six DW images, each corresponding to different diffusion directions and containing EC distortions that are corrected by a specific set of EC parameters. Each respective set ...
We have investigated the role of 3 ,5 -cyclic-adenosine-monophosphate (cAMP) in mediating the coupling between energy metabolism and cell cycle progression in both synchronous cultures and oscillating continuous cultures of Saccharomyces cerevisiae. For the first time, a peak in intracellular cAMP was shown to precede the observed breakdown of trehalose and glycogen during cell cycle-related oscillations. Measurements in synchronous cultures demonstrated that this peak can be associated with the cell cycle dynamics of cAMP under conditions of glucose-limited growth, which was found to differ significantly from that observed in synchronous glucoserepressed cultures. Our results support the notion that cAMP plays a major role in mediating the integration of energy metabolism and cell cycle progression, both in the single cell and during cell cycle-related oscillations in continuous culture, respectively. Evidence is presented that the dynamic behaviour of intracellular cAMP during the cell cycle is modulated depending on nutrient supply. The implications of these findings regarding the role of cAMP in regulating cell cycle progression and energy metabolism are discussed.
Increased responding to drug-associated stimuli (cue reactivity) and an inability to tolerate delayed gratification (reward impulsivity) have been implicated in the development and maintenance of drug addiction. Whereas data from animal studies suggest that both the dopamine and opioid system are involved in these two reward-related processes, their role in humans is less clear. Moreover, dopaminergic and opioidergic drugs have not been directly compared with regard to these functions, even though a deeper understanding of the underlying mechanisms might inform the development of specific treatments for elevated cue reactivity and reward impulsivity. In a randomized, double-blind, between-subject design we administered the selective dopamine D2/D3 receptor antagonist amisulpride (400 mg, n=41), the unspecific opioid receptor antagonist naltrexone (50 mg, n=40) or placebo (n=40) to healthy humans and measured cue-induced responding with a Pavlovian-instrumental transfer task and reward impulsivity with a delay discounting task. Mood was assessed using a visual analogue scale. Compared with placebo, amisulpride significantly suppressed cue-induced responding and reward impulsivity. The effects of naltrexone were similar, although less pronounced. Both amisulpride and naltrexone decreased average mood ratings compared with placebo. Our results demonstrate that a selective blockade of dopamine D2/D3 receptors reduces cue-induced responding and reward impulsivity in healthy humans. Antagonizing μ-opioid receptors has similar effects for cue-induced responding and to a lesser extent for reward impulsivity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.