Simple tone discriminations are disrupted following experimental frontal traumatic brain injury in rats.

PRIMARY OBJECTIVE: To assess cognitive deficits in a rat model of brain injury. RESEARCH DESIGN: Cognitive deficits are some of the most pervasive and enduring symptoms of frontal traumatic brain injury (TBI) in human patients. In animal models, the assessment of cognitive deficits from TBI has primarily been limited to tests of spatial learning. Recently, simple discrimination performance has been shown to be sensitive to frontal brain damage. The current study provides a detailed characterization of deficits in a two-choice tone discrimination following a bilateral frontal controlled cortical impact injury. METHODS AND PROCEDURES: Rats were trained on a two-tone discrimination task in a standard operant chamber, then either a frontal brain injury was delivered or sham procedures performed. Following recovery, they were re-tested on the discrimination task and then tested on a reversal of the discrimination. MAIN OUTCOMES AND RESULTS: Frontal injury caused substantial deficits in responding and discrimination accuracy as well as an increase in side bias. CONCLUSIONS: Based on the outcomes seen in this study, discrimination and other operant tasks may provide a sensitive tool to assess the effect of therapeutic agents on cognitive deficits in animal models, which could lead to improved characterization of deficits and yield an improved assessment tool to aid in drug discovery.

Behavior Analysts' Relationship to Relating Relations: A Survey on Perceptions, Acceptability, Knowledge, and Capacity for Derived Stimulus Relations Research and Practice.

The study and application of procedures that result in stimulus relations via relational frame theory (RFT) and stimulus equivalence (applied as equivalence-based instruction; EBI), have made tremendous strides in contemporary behavior analysis. However, applications at scale lag basic and translational research. We turn our attention inward to investigate potential causes. We replicated and extended Enoch and Nicholson (Behavior Analysis in Practice, 13(3), 609-617, 2020) by conducting a survey of behavior analysts (n = 129) to determine their perceptions, experiences, and barriers in carrying out research and practice based on RFT and EBI. Participants indicated an interest in RFT and EBI, and mostly perceive both within the scope of behavior analysis. A majority of behavior analysts reported formal education in EBI (78.3%), in contrast to a minority in RFT (15.5%). Adoption of procedures derived from RFT and EBI may be in proportion to formal education. Compounded with a lack of accuracy on basic knowledge questions, there is a potential gap in capacity in the field in addressing behavior related to complex verbal behavior.

Altered states: the impact of immediate craving on the valuation of current and future opioids.

Based on prior research showing that people underestimate the influence of motivational states they are not currently experiencing, we predicted and found that heroin addicts would value an extra dose of the heroin substitute Buprenorphine more highly when they were currently craving (right before receiving BUP) than when they were currently satiated (right after receiving BUP) -- even when the extra BUP was to be received 5 days later. If addicts cannot appreciate the intensity of craving when they are not currently experiencing it, as these results suggest, it seems unlikely that those who have never experienced craving could predict its motivational force. Under-appreciation of craving by non-addicts may contribute to initial decisions to experiment with drugs.

Contextual control of delay discounting by pathological gamblers.

The present study demonstrated the relative impact of gambling and nongambling contexts on the degree of delay discounting by pathological gamblers. We used a delay-discounting task with 20 pathological gamblers in and out of the natural context in which they regularly gambled. For 16 of the 20 participants, it appeared that the difference of context altered the subjective value of delayed rewards, thereby producing relative changes in delay-discounting rates that were generally consistent with a hyperbolic model of intertemporal choice. The current data suggest that empirically derived k values from delay-discounting tasks are context sensitive and are not constant across various settings for the individual. Implications for future transitional research on addictive disorders generally, and gambling specifically, are discussed.

Buprenorphine treatment for opioid dependence: the relative efficacy of daily, twice and thrice weekly dosing.

This randomized clinical trial evaluated the relative efficacy of three buprenorphine dosing schedules. Opioid-dependent adults were randomly assigned to receive buprenorphine seven, 3 or 2 days per week for 24 weeks. Daily maintenance doses were 4, 8, 10, or 12 mg of the sublingual buprenorphine solution. Participants who attended the clinic daily received a maintenance dose of buprenorphine daily. Participants who attended the clinic thrice weekly received double their maintenance dose on Monday and Wednesday, followed by a triple dose on Friday. Participants who attended the clinic twice weekly received quadruple their maintenance dose of buprenorphine on Monday and triple their maintenance dose on Friday. Results demonstrated that all dosing regimens were of comparable efficacy in promoting treatment retention, opioid and cocaine abstinence, and reductions in HIV risk behavior (especially as related to drug use) and severity of life problems. Predictor analyses identified sub-populations of opioid-dependent individuals that may have a more positive treatment outcome under each buprenorphine dosing condition. Less-than-daily dosing schedules may provide the opportunity for treatment programs to serve a greater number of opioid-dependent patients and reduce the risk of medication diversion, which may, in turn, have a positive impact on community support of science-based treatment for opioid-dependence.

Mild opioid deprivation increases the degree that opioid-dependent outpatients discount delayed heroin and money.

RATIONALE: A growing literature suggests that excessive temporal discounting of delayed rewards may be a contributing factor in the etiology of substance abuse problems. Little is known, however, about how drug deprivation may affect temporal discounting of delayed rewards by drug-dependent individuals. OBJECTIVE: To examine the extent to which opioid deprivation affects how opioid-dependent individuals discount small, medium and large quantities of delayed heroin and money. METHODS: Thirteen opioid-dependent individuals maintained on buprenorphine completed a hypothetical choice task in which they choose between a constant delayed reward amount and an immediate reward amount that was adjusted until they expressed indifference between both outcomes. The task was completed for three values of heroin and money rewards during eight sessions under conditions of opioid deprivation (four sessions) and satiation (four sessions). RESULTS: Across conditions, hyperbolic functions provided a good fit for the discounting data. Degree of discounting was significantly higher when subjects were opioid deprived. Consistent with previous findings, degree of discounting was higher for heroin than money and inversely related to the magnitude of the reward. CONCLUSION: Opioid deprivation increased the degree to which dependent individuals discounted delayed heroin and money. Understanding the conditions that affect how drug-dependent individuals discount delayed rewards might help us understand the myopic choices made by such individuals and help improve treatment outcomes.

Delay discounting by pathological gamblers.

Discounting of delayed rewards by pathological gamblers was compared to discounting of delayed rewards by matched control nongambling participants. All participants completed a hypothetical choice task in which they made repeated choices between dollars 1,000 available after a delay and an equal or lesser amount of money available immediately. The delay to the large amount of money was varied from 1 week to 10 years across conditions. Indifference points between immediate money and delayed money were identified at each delay condition by varying the amount of immediate money across choice trials. For the majority of participants, indifference points decreased monotonically across delays. Overall, gamblers discounted the delayed rewards more steeply than did control participants.

Deficits in discrimination after experimental frontal brain injury are mediated by motivation and can be improved by nicotinamide administration.

One of the largest challenges in experimental neurotrauma work is the development of models relevant to the human condition. This includes both creating similar pathophysiology as well as the generation of relevant behavioral deficits. Recent studies have shown that there is a large potential for the use of discrimination tasks in rats to detect injury-induced deficits. The literature on discrimination and TBI is still limited, however. The current study investigated motivational and motor factors that could potentially contribute to deficits in discrimination. In addition, the efficacy of a neuroprotective agent, nicotinamide, was assessed. Rats were trained on a discrimination task and motivation task, given a bilateral frontal controlled cortical impact TBI (+3.0 AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI resulted in large deficits in discrimination and motivation. No deficits were observed on gross motor measures; however, the vehicle group showed impairments in fine motor control. Both injured groups were impaired on the reference memory MWM, but only nicotinamide-treated rats were impaired on the working memory MWM. Nicotinamide administration improved performance on discrimination and motivation measures. Experiment 2 evaluated retraining on the discrimination task and suggested that motivation may be a large factor underlying discrimination deficits. Retrained rats improved considerably on the discrimination task. The tasks evaluated in this study demonstrate robust deficits and may improve the detection of pharmaceutical effects by being very sensitive to pervasive cognitive deficits that occur after frontal TBI.

Attention and psychophysics in the development of stimulus control.

Rats responded in a six-stimulus, two-response temporal classification procedure. A successive-reversal design was used in which the relationship between stimulus class (short vs. long) and correct comparison location (left or right) reversed every 15 sessions. After several reversals, the relative probability of reinforcement for each correct classification was manipulated across subsequent reversals. In each condition, the asymptotic level of preference for the comparison location (response bias) correlated with the greater probability of reinforcement was demonstrated in the first session following a reversal, whereas discrimination accuracy took several more sessions to return to asymptotic levels. A modified version of the attending-augmented Davison-Nevin-Alsop (Davison & Nevin, 1999) model offered by Nevin, Davison, & Shahan (2005) provided an accurate description of the reacquisition data. The comparison-attending parameters remained high and relatively constant following reversals, while sample-attending parameters initially decreased following reversals, and then increased gradually across sessions. These findings support key assumptions of the attending model; sample- and comparison-attending are independent processes that modulate the expression of discriminative control exerted by those stimuli over operant behavior.

Sensitivity to changing contingencies in an impulsivity task.

Using a video-game-based escalating interest task, participants repeatedly encountered a reward that gradually increased in value over a 10-second interval. Responding early in the interval netted less immediate reward than responding later in the interval. Each participant experienced four different reward contingencies for waiting. These contingencies were changed three times as the experiment proceeded. Behavior tracked these changing contingencies, but wait times reflected long-term carryover from the previously assigned contingencies. Both the tendency to respond slowly and the optimality of behavior were affected by the order of contingencies experienced. Demographic variables only weakly predicted behavior, and delay discounting rate in a hypothetical money choice task predicted choice only when the contingencies in the game were weaker.

Magnitude effects for experienced rewards at short delays in the escalating interest task.

A first-person shooter video game was adapted for the study of choice between smaller sooner and larger later rewards. Participants chose when to fire a weapon that increased in damage potential over a short interval. When the delay to maximum damage was shorter (5-8 s), people showed greater sensitivity to the consequences of their choices than when the delay was longer (17-20 s). Participants also evidenced a magnitude effect by waiting proportionally longer when the damage magnitudes were doubled for all rewards. The experiment replicated the standard magnitude effect with this new video game preparation over time scales similar to those typically used in nonhuman animal studies and without complications due to satiation or cost.

Rapid acquisition of bias in signal detection: dynamics of effective reinforcement allocation.

We investigated changes in bias (preference for one response alternative) in signal detection when relative reinforcer frequency for correct responses varied across sessions. In Experiment 1, 4 rats responded in a two-stimulus, two-response identification procedure employing temporal stimuli (short vs. long houselight presentations). Relative reinforcer frequency varied according to a 31-step pseudorandom binary sequence and stimulus duration difference varied over two values across conditions. In Experiment 2, 3 rats responded in a five-stimulus, two-response classification procedure employing temporal stimuli. Relative reinforcer frequency was varied according to a 36-step pseudorandom ternary sequence. Results of both experiments were analyzed according to a behavioral model of detection. The model was extended to incorporate the effects of current and previous session reinforcer frequency ratios on current-session performance. Similar to findings with concurrent schedules, effects on bias of relative reinforcer frequency were highest for the current session. However, carryover from reinforcer ratios of previous sessions was evident. Generally, the results indicate that bias can come under control of frequent changes in relative reinforcer frequency in both identification and classification procedures.

Deciding when to "cash in" when outcomes are continuously improving: an escalating interest task.

A first-person shooter video game was adapted for the study of choice between smaller sooner and larger later outcomes. Participants chose when to fire a weapon that increased in damage potential over a 10s interval, an escalating interest situation. Across two experiments, participants demonstrated sensitivity to the nature of the mathematical function that defined the relationship between waiting and damage potential. In Experiment 1, people tended to wait longer when doing so allowed them to eliminate targets more quickly. In Experiment 2, people tended to wait longer to increase the probability of a constant magnitude outcome than to increase the magnitude of a 100% certain outcome that was matched for the same expected value (i.e., probability times magnitude). The two experiments demonstrated sensitivity to the way in which an outcome improves when the outcome is continuously available. The results also demonstrate that this new video game task is useful for generating sensitivity to delay to reinforcement over time scales that are typically used in nonhuman animal studies.