A Rapid Procedure to Assess Shifts in Discriminative Control Over Drinking During Recovery-Like Behavior.

BACKGROUND: Previously, we reported that recovery-like behavior decreases stimulus control over drinking, and this likely plays a role in the clinical observation that longer recovery increases relapse resistance. Those studies were conducted using a procedure that required repeated assessment, preventing a longitudinal analysis of the changes in stimulus control over time in each individual. Here we recapitulate those results and extend them to female rats using a more efficient procedure that allows repeated assessment of changes in stimulus control over drinking during recovery. METHODS: Under a multiple concurrent schedule, rats were trained to reliably respond predominately for ethanol (concurrent Ethanol FR5, Food FR150) in the presence of one stimulus and for food (concurrent Ethanol FR5, Food FR5) in the presence of another stimulus. Stimuli were either lights or tones, depending on the group. After that, a drinking phase in which only the stimulus occasioning ethanol responding was presented (10 or 20 sessions) followed by recovery-like sessions in which only the stimulus occasioning food responding was presented. During these sessions, rats were exposed to the ethanol stimulus under extinction during the first component on sessions 0, 1, 2, 4,8, and 16. The number of food responses during these stimulus exposures prior to the first 5 ethanol responses was the primary measure. RESULTS: Consistent with the earlier procedure, the number of food responses during ethanol tests increased as a function of the number of recovery sessions completed, regardless of whether the stimuli were visual or auditory. However, there were no significant effects of extended alcohol exposure or sex. CONCLUSIONS: A rapid procedure consistent with the earlier procedure and clinical evidence was developed in which stimulus control over drinking decreased following longer periods of recovery. Under conditions tested, stimulus type, length of drinking history and sex did not affect this relationship.

Effects of an ethanol-paired conditioned stimulus on responding for ethanol suppressed by a conditioned-taste-aversion.

Ethanol-Paired Conditioned Stimuli (CS) can increase ethanol-responding either in extinction or occurring at low rates late in a session. To examine the generality of CS-induced increases in ethanol-responding, we examined whether a CS could increase responding suppressed by Conditioned-Taste-Aversion (CTA), which presumably suppresses responding by changing ethanol's valence from positive to negative. Rats were trained to respond for ethanol under a Random Interval (RI) schedule. We then removed the lever and paired Random-Time ethanol deliveries with illumination of a stimulus light (i.e., CS) for 10 sessions. Results were compared with a Truly Random Control group, in which the light and ethanol deliveries occurred independently. In a subsequent experiment, rats were treated similarly, except the light served as a discriminative stimulus, as the lever was extended and ethanol deliveries were available under a RI during light presentations. After this training, the lever was returned and rats again responded for ethanol. Subsequently, sessions were followed by LiCl administration. When responding reached low levels, LiCl administration stopped and the light was occasionally illuminated during the session. Responding during the light presentation was compared to responding during the period preceding light presentation. Responding partially recovered across 10 sessions and was greater during light presentations than in the period before it in all three groups. Increases were not reliably different between the groups, indicating that explanations for these increases such as CS-induced increases in motivation or approach toward the light are unlikely to be correct. The most likely explanation for these light-induced increases is that during sessions in which the light had been presented previously, LiCl had never been presented and thus, the light had come to signal that ethanol was safe to drink.

Shifts in stimulus control over opioid use with increasing periods of recovery.

BACKGROUND: Periods of engaging in an alternative behavior diminishes behavioral control by stimuli occasioning alcohol use. This increase in relapse resistance with increasing recovery suggests that changing stimulus control over substance use may be a mechanism responsible for decreased relapse rates with longer recovery. However, the generality of this phenomenon to other drugs of abuse, including opioid self-administration, remains unclear. This study tests the generality of these findings with etonitazene to determine whether the shift in attention represents a behavioral process that generalizes from conditions we previously reported. METHODS: Five adult male Lewis rats were trained to respond on levers under two stimulus conditions; high-cost food (food FR150 and etonitazene FR5) and low-cost food (both food and etonitazene FR 5). Next, only the high-cost food stimulus (occasioning etonitazene responding) was presented for 20 sessions (Use Phase) followed by 9 sessions in which only the low-cost food stimulus (occasioning food responding) was presented (Recovery Phase). During the Recovery Phase, testing occurred during the first component of sessions 0, 1, 2, 4, and 8 when rats were re-exposed to the high-cost food stimulus. The number of food responses prior to completing the etonitazene response requirement during this stimulus exposure was the primary measure. RESULTS: Food responses during stimulus re-exposure increased significantly as a function of recovery sessions completed with a slope [95 % CI] of 2.49 responses/recovery session [0.16, 4.81]. The average number of etonitazene deliveries per use session was 32 ± 6.6 or an average daily dose of 48.8 ± 10.1 µg/kg. During Recovery Phase, etonitazene deliveries decreased to 2.4 ± 1 or 3.6 ± 1.5 µg/kg. CONCLUSION: The decrease in stimulus control observed for ethanol self-administration appears to generalize to opioid self-administration, indicating this change in stimulus control may play a general role in recovery.

Ethanol-paired conditioned stimulus effects on concurrent reinforced responding for ethanol and food.

The influence of Pavlovian Conditioned Stimuli (CS) on ethanol self-administration and choice between ethanol and an alternative are potentially important. Ethanol-paired CS might increase ethanol self-administration, especially when it has been reduced during recovery, though the selectivity of these increases has been questioned. To date, one study examined the effects of an ethanol-paired CS on ethanol choice and found that the CS increased ethanol-responding more than food-responding when both were in extinction. However, it remains unclear whether ethanol-paired CS increase ethanol-choice that is not in extinction. Here, we examine the effects of an ethanol-paired CS on ethanol-choice when both food- and ethanol-responding are reinforced. Sixteen adult male Lewis rats were trained on a concurrent schedule to respond for ethanol on one lever and for food on the other lever. Ethanol was available under an FR 5 schedule, and food was available under an FR schedule that was adjusted for each rat to earn an equal number of food and ethanol deliveries. Then, 2-min light presentations were paired with an RT 25-sec schedule of ethanol delivery for 10 sessions in the absence of both levers. After this, subjects were placed back on the concurrent schedule for one session, then five sessions with the CS being present or absent on each trial of the concurrent schedule occurred. Rats learned to respond on one lever for ethanol and on the other for food and earned similar numbers of ethanol and food deliveries. During Pavlovian Conditioning, the number of head entries into the head-entry detector was higher in the presence of the CS than in its absence. In the test sessions, rats made more ethanol responses in the presence of the CS than in its absence. However, this effect was small and did not increase the amount of ethanol earned. Thus, ethanol-paired CS could increase ethanol-responding under a choice procedure but did not increase ethanol consumption meaningfully under the studied conditions.

Reduced alcohol use increases drink-refusal self-efficacy: Evidence from a contingency management study for DWI arrestees.

BACKGROUND: Several therapies and interventions to reduce drinking first target drink-refusal self-efficacy (DRSE) to influence drinking behavior. While higher self-efficacy scores are correlated with better outcomes, it is unclear that increased self-efficacy is the causative step leading to improved outcomes. Instead, this correlation may result from reduced drinking that increased self-efficacy. The current study sought to understand how changes in drinking behavior can influence DRSE. METHODS: Data were from 211 driving while intoxicated (DWI) arrestees participating in an 8-week contingency management (CM) study to reduce drinking. Some of participants were mandated by the courts to wear transdermal alcohol monitoring devices (Mandated group) and some were not mandated (Non Mandated group). All wore a transdermal alcohol monitor during the 8-week study and were randomized to CM or a Control condition stratified by the mandate group. Participants completed weekly assessments of DRSE. Group-based trajectory-modeling identified three drinking behavior trajectory groups. RESULTS: While there were no differences in baseline DRSE between the three trajectory groups, participants in the low- and moderate-frequency drinking behavior groups significantly increased DRSE across the study. CONCLUSION: The present study indicates that being able to maintain abstinence or reduce heavy drinking may increase DRSE.

Conditioned stimulus effects on paired or alternative reinforcement depend on presentation duration: Implications for conceptualizations of craving.

Conditioned stimuli (CS) associated with alcohol ingestion are thought to play a role in relapse by producing a craving that in turn increases motivation to drink which increases ethanol-seeking and disrupts other ongoing behavior. Alternatively, such CS may provide information indicating a likely increase in the density of the paired unconditioned stimulus and simultaneously elicit behavior that may be incompatible with other ongoing behavior, i.e., approach toward the CS. To explore these possibilities, rats were trained to respond for ethanol or food in two different components of the same session after which a light above the ethanol-lever was lighted twice during each component and each light presentation was followed by ethanol delivery. The duration of this CS was 10 s initially and then increased to 30 s, then to 100 s, and finally returned to 30 s. The change in responding for ethanol or food was compared to a matched period immediately preceding CS presentation. The CS presentation increased responding to ethanol, and this effect increases with longer CS presentations. In contrast, the CS presentation decreased responding to food, and this effect decreases with longer CS presentations. These results appear to support the informational account of CS action rather than simply a change in the motivation to seek and consume ethanol. This suggests that craving as it is commonly understood likely represents multiple behavioral processes, not simply increased desire for alcohol and that reports of craving likely reflect labeling based upon past experiences rather than a cause of future drug-taking.

Small bowel diverticulosis: imaging appearances, complications, and pitfalls.

Diverticula of the small bowel can be categorised as true, with Meckel's being the only example, or false. False small bowel diverticula (SBD) are acquired through herniation of the internal layers of the bowel wall through the muscularis propria. Peri-ampullary duodenal diverticula are a well-recognised example; however, the importance of more distal SBD in the jejunum and ileum is underappreciated, and they are under-reported on cross-sectional imaging. SBD are a known cause of anaemia, malabsorption, and diarrhoea, and there are myriad complications of SBD and Meckel's diverticula, which range in severity from inflammation and perforation to haemorrhage, tumour formation, and obstruction. Before the advent of computed tomography (CT), SBD were readily diagnosed on fluoroscopic oral contrast studies; however, radiologists are less comfortable with their cross-sectional imaging appearances. This imaging review combines our experience of multiple proven cases, with illustrative diagrams and radiological images of SBD to provide distinct imaging characteristics, allowing for confident diagnosis of SBD and their numerous complications. We discuss the importance of SBD as a cause of benign, non-surgical pneumoperitoneum. We additionally provide important pitfalls to be aware of such as SBD masquerading as other abnormalities.

Ethanol-paired stimuli can increase reinforced ethanol responding.

While ethanol-paired stimuli are frequently postulated to increase drinking motivation and thus increase ethanol responding and precipitate relapse, no study has demonstrated increases in ethanol-reinforced responding following presentation of an ethanol-paired stimulus that had not previously been part of a contingent relationship. Previous studies have shown that food-paired stimuli can increase food responding that is at low rates and increase food consumption in food-sated rats. In Experiment 1, we show that an ethanol-paired stimulus can increase ethanol responding that is at low levels late in the experimental session, presumably due to satiation. However, these increases may have resulted from either associative or non-associative mechanisms. In Experiment 2, we compared the effects of an ethanol-paired stimulus to those of the same stimulus in a Truly-Random-Control group. In a Truly-Random-Control, the stimulus and ethanol each are presented on independent random schedules, and thus any differences between the effects of the stimulus in the experimental and control groups is likely attributable to the association between the stimulus and ethanol. The stimulus increased ethanol-reinforced responding in both the experimental and control groups, but these increases were greater in the experimental than the control group. Thus, both stimulus-change and the pairing of the stimulus with ethanol may result in increases in ethanol-reinforced responding.

Further psychometric analysis of the 20-item Partner Interaction Questionnaire in an adult sample of smokers.

The 20-item Partner Interaction Questionnaire (PIQ-20) is frequently used to assess social support for adults wanting to stop smoking. Given that social support may play a significant role in quitting success, there is a need to understand the structure and psychometric properties of assessment instruments designed to measure the construct of partner support. The current study examined the psychometric properties of the PIQ-20 when used to assess the frequency of partner behaviors. The study participants included 380 adult volunteers (M age = 41 years, SD = 12; 58% male). To assess internal consistency, we used both the traditional coefficient-alpha and the latent variable modeling composite reliability (coefficient-ρ) procedures. We conducted independent factor analytic methods to address issues of dimensionality and scoring of responses to the PIQ-20 items. Also, we used an item response theory modeling procedure to examine the specificity of scores on the items. Reliability estimates for the PIQ-20 subscale scores were adequate (values ≥.70). The bifactor analysis supported deriving a total score for each subscale. Item response theory modeling demonstrated that the discrimination (a-slope) parameter for each subscale item was significantly different from zero. The majority of items were associated strongly with their respective subscales. Twelve items were identified that could be adopted as a potential short form of the PIQ-20. The PIQ-20 or short form provides an opportunity for assessing positive and negative partner support simultaneously. There is empirical support for the dimensional structures and scoring of responses for both versions of the instrument. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Holographic imaging of electromagnetic fields via electron-light quantum interference.

Holography relies on the interference between a known reference and a signal of interest to reconstruct both the amplitude and the phase of that signal. With electrons, the extension of holography to the ultrafast time domain remains a challenge, although it would yield the highest possible combined spatiotemporal resolution. Here, we show that holograms of local electromagnetic fields can be obtained with combined attosecond/nanometer resolution in an ultrafast transmission electron microscope (UEM). Unlike conventional holography, where signal and reference are spatially separated and then recombined to interfere, our method relies on electromagnetic fields to split an electron wave function in a quantum coherent superposition of different energy states. In the image plane, spatial modulation of the electron energy distribution reflects the phase relation between reference and signal fields. Beyond imaging applications, this approach allows implementing quantum measurements in parallel, providing an efficient and versatile tool for electron quantum optics.

Ultrafast generation and control of an electron vortex beam via chiral plasmonic near fields.

Vortex-carrying matter waves, such as chiral electron beams, are of significant interest in both applied and fundamental science. Continuous-wave electron vortex beams are commonly prepared via passive phase masks imprinting a transverse phase modulation on the electron's wavefunction. Here, we show that femtosecond chiral plasmonic near fields enable the generation and dynamic control on the ultrafast timescale of an electron vortex beam. The vortex structure of the resulting electron wavepacket is probed in both real and reciprocal space using ultrafast transmission electron microscopy. This method offers a high degree of scalability to small length scales and a highly efficient manipulation of the electron vorticity with attosecond precision. Besides the direct implications in the investigation of nanoscale ultrafast processes in which chirality plays a major role, we further discuss the perspectives of using this technique to shape the wavefunction of charged composite particles, such as protons, and how it can be used to probe their internal structure.

Author Correction: Attosecond coherent control of free-electron wave functions using semi-infinite light fields.

The authors became aware of a mistake in the original version of this Article. Specifically, an extra factor γ was incorrectly included in a number of mathematical equations and expressions. As a result of this, a number of changes have been made to both the PDF and the HTML versions of the Article. A full list of these changes is available online.

Effects of rat strain and method of inducing ethanol drinking on Pavlovian-Instrumental-Transfer with ethanol-paired conditioned stimuli.

Ethanol-paired conditioned stimuli (CSs) are widely thought to invigorate ethanol responding, and thus, precipitate relapse to drinking. However, preclinical studies investigating this issue using Pavlovian-Instrumental-Transfer (PIT) procedures have had mixed results, with some studies finding PIT while others did not. The studies failing to show PIT used Lewis rats and induced ethanol drinking using a post-prandial drinking procedure. The present experiments examined whether either of these two variables influenced the magnitude of PIT observed. In the first experiment, ethanol drinking in Lewis rats was induced using either sucrose fading or post-prandial drinking. In the second experiment, ethanol drinking was induced using post-prandial drinking in either Long-Evans Hooded or Lewis rats. In both experiments, rats were trained to respond for ethanol under a random interval schedule. Subsequently with the lever removed, 2-min light presentations were paired with ethanol deliveries. Finally, with the lever returned, the effect of light presentations on responding was tested while responding was in extinction. Light presentations similarly affected responding in Lewis rats regardless of the method of drinking induction. Likewise, light presentations similarly affected responding in both Lewis and Long-Evans Hooded rats. Neither ethanol induction method nor rat strain affected the magnitude of PIT observed, and thus, neither likely explains previous failures to observe PIT with ethanol-maintained behavior.

Modernizing and Expanding the NASA Space Geodesy Network to Meet Future Geodetic Requirements.

NASA maintains and operates a global network of Very Long Baseline Interferometry (VLBI), Satellite Laser Ranging (SLR), and Global Navigation Satellite System (GNSS) ground stations as part of the NASA Space Geodesy Program. The NASA Space Geodesy Network (NSGN) provides the geodetic products that support Earth observations and the related science requirements as outlined by the US National Research Council (NRC 2010, 2018). The Global Geodetic Observing System (GGOS) and the NRC have set an ambitious goal of improving the Terrestrial Reference Frame (TRF) to have an accuracy of 1 millimeter and stability of 0.1 millimeters per year, an order of magnitude beyond current capabilities. NASA and its partners within GGOS are addressing this challenge by planning and implementing modern geodetic stations co-located at existing and new sites around the world. In 2013, NASA demonstrated the performance of its next-generation systems at the prototype next-generation core site at NASA's Goddard Geophysical and Astronomical Observatory in Greenbelt, Maryland. Implementation of a new broadband VLBI station in Hawaii was completed in 2016. NASA is currently implementing new VLBI and SLR stations in Texas and is planning the replacement of its other aging domestic and international legacy stations. In this article, we describe critical gaps in the current global network and discuss how the new NSGN will expand the global geodetic coverage and ultimately improve the geodetic products. We also describe the characteristics of a modern NSGN site and the capabilities of the next-generation NASA SLR and VLBI systems. Finally, we outline the plans for efficiently operating the NSGN by centralizing and automating the operations of the new geodetic stations.

Attosecond coherent control of free-electron wave functions using semi-infinite light fields.

Light-electron interaction is the seminal ingredient in free-electron lasers and dynamical investigation of matter. Pushing the coherent control of electrons by light to the attosecond timescale and below would enable unprecedented applications in quantum circuits and exploration of electronic motions and nuclear phenomena. Here we demonstrate attosecond coherent manipulation of a free-electron wave function, and show that it can be pushed down to the zeptosecond regime. We make a relativistic single-electron wavepacket interact in free-space with a semi-infinite light field generated by two light pulses reflected from a mirror and delayed by fractions of the optical cycle. The amplitude and phase of the resulting electron-state coherent oscillations are mapped in energy-momentum space via momentum-resolved ultrafast electron spectroscopy. The experimental results are in full agreement with our analytical theory, which predicts access to the zeptosecond timescale by adopting semi-infinite X-ray pulses.

Laser-Induced Skyrmion Writing and Erasing in an Ultrafast Cryo-Lorentz Transmission Electron Microscope.

We demonstrate that light-induced heat pulses of different duration and energy can write Skyrmions in a broad range of temperatures and magnetic field in FeGe. Using a combination of camera-rate and pump-probe cryo-Lorentz transmission electron microscopy, we directly resolve the spatiotemporal evolution of the magnetization ensuing optical excitation. The Skyrmion lattice was found to maintain its structural properties during the laser-induced demagnetization, and its recovery to the initial state happened in the sub-µs to µs range, depending on the cooling rate of the system.

Addiction as a BAD, a Behavioral Allocation Disorder.

Addiction is continued drug use despite its harm. As one always has alternatives, addiction can be construed as a decision to allocate behavior to drug use. While decision making is commonly discussed and studied as if it resulted from deliberative, evaluative processes, such processes are actually only rarely involved in behavior allocation. These deliberative processes are too slow, effortful and inefficient to guide behavior other than when necessary. Rather, most actions are guided by faster, more automatic processes, often labeled habits. Habits are mostly adaptive, and result from repeated reinforcement leading to over-learned behavior. Habitual behavior occurs rapidly in response to particular contexts, and the behavior occurring first is that which occurs, i.e., the behavior that is decided upon. Thus, as drug use becomes habitual, drug use is likely to be chosen over other available activities in that particular context. However, while drug use becoming habitual is necessary for addiction to develop, it is not sufficient. Typically, constraints limit even habitual drug use to safer levels. These constraints might include limiting occasions for use; and, almost always, constraints on amount consumed. However, in a minority of individuals, drug use is not sufficiently constrained and addiction develops. This review discusses the nature of these constraints, and how they might fail. These failures do not result from abnormal learning processes, but rather unfortunate interactions between a person and their environment over time. These accumulate in the maladaptive allocation of behavior to drug use. This Behavior Allocation Disorder (BAD) can be reversed; occasionally easily when the environment significantly changes, but more often by the arduous application of deliberative processes generally absent from decision making. These deliberative processes must continue until new more adaptive habits become the most probable behavior in the contexts encountered. As alternatives to drug use become the most probable behavior, relapse risk diminishes.

Nicotine as a discriminative stimulus for ethanol use.

Abused drugs reinforce behavior; i.e., they increase the probability of the behavior preceding their administration. Abused drugs can also act as discriminative stimuli; i.e., they can set the occasion for responding reinforced by another event. Thus, one abused drug could come to set the occasion for the use of another and this functional relationship may play a role in polysubstance abuse, where common patterns of use could result in this relationship. Here we establish nicotine (0.4mg/kg, ip 5-min pre-session) as a discriminative stimulus for behavior reinforced by ethanol (0.1ml 8% w/v po, versus food) and determine the ability of nicotine (0.02-0.4mg/kg), varenicline (0.1-3.0mg/kg), and ethanol (250 and 500mg/kg) to control responding for ethanol. We compare these results to those from rats where nicotine signaled food was available (and ethanol was not). Nicotine came to function as a discriminative stimulus. Nicotine and varenicline produced dose-dependent increases in responding on the nicotine-appropriate lever while ethanol produced responding on the vehicle-appropriate lever. Whether this responding occurred on the lever that produced ethanol or food access depended on the training condition. These results demonstrate that a drug can come to set the occasion for use of another and suggest that this behavioral mechanism could play an important role in the maintenance of and recovery from polysubstance abuse, depending on the pattern of use.

Frustration stress (unexpected loss of alternative reinforcement) increases opioid self-administration in a model of recovery.

PURPOSE: Engaging in alternative activities in the context where opioid use had occurred can constrain opioid use and helps to maintain recovery. However, "frustration stress" that occurs when contingencies on these alternative activities unexpectedly change (e.g., job loss or divorce) is thought to threaten recovery by prompting a return to drug use. Yet it remains unclear whether frustration stress can result in a return to drug use, and if so, whether it returns to prior levels or to even greater levels. PROCEDURES: We examine the impact of unsignaled extinction of alternative reinforcement on opioid use. Rats were trained to respond for an etonitazene solution (5µg/ml, p.o.), then for food in alternating daily sessions. Subsequently, food and etonitazene were made concurrently available. Under concurrent availability conditions, rats were exposed to 1, 2, or 4 sessions of unsignaled food extinction, and effects on responding for etonitazene and food measured. FINDINGS: When etonitazene was the only reinforcer available, rats earned 58.3±20.3µg/kg/session (mean±S.E.M.). When food was available in alternating sessions, etonitazene earned was unchanged (65.3±19.2µg/kg/session). Concurrent food availability decreased etonitazene earned (13.5±4.5µg/kg/session). Unsignaled food extinction returned etonitazene earnedto levels similar to (60.5±18.4µg/kg/session), but not greater than, those observed previously when etonitazene alone was available. CONCLUSIONS: Unsignaled extinction of alternative behavior controlling opioid use can result in increased opioid use, but this use does not rise beyond previous levels observed when opioid use is unconstrained by alternative reinforced behavior.