Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats.

Ketamine (KET), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, has rapid onset of antidepressant effects in Treatment-Resistant Depression patients and repeated infusions are required to sustain its antidepressant properties. However, KET is an addictive drug, and so more preclinical and clinical research is needed to assess the safety of recurring treatments in both sexes. Thus, the aim of this study was to investigate the reinforcing properties of various doses of KET (0-, 0.125-, 0.25-, 0.5 mg/kg/infusion) and assess KET's cue-induced reinstatement and neuronal activation in both sexes of Long Evans rats. Neuronal activation was assessed using the protein expression of the immediate early gene cFos in the nucleus accumbens (Nac), an important brain area implicated in reward, reinforcement and reinstatement to most drug-related cues. Our findings show that KET has reinforcing effects in both male and female rats, albeit exclusively at the highest two doses (0.25 and 0.5 mg/kg/infusion). Furthermore, we noted sex differences, particularly at the highest dose of ketamine, with female rats displaying a higher rate of self-administration. Interestingly, all groups that self-administered KET reinstated to drug-cues. Following drug cue-induced reinstatement test in rats exposed to KET (0.25 mg/kg/infusion) or saline, there was higher cFos protein expression in KET-treated animals compared to saline controls, and higher cFos expression in the core compared to the shell subregions of the Nac. As for reinstatement, there were no notable sex differences reported for cFos expression in the Nac. These findings reveal some sex and dose dependent effects in KET's reinforcing properties and that KET at all doses induced similar reinstatement in both sexes. This study also demonstrated that cues associated with ketamine induce comparable neuronal activation in the Nac of both male and female rats. This work warrants further research into the potential addictive properties of KET, especially when administered at lower doses which are now being used in the clinic for treating various psychopathologies.

Examining patterns suggestive of acquisition during functional analyses: A consecutive controlled series of 116 cases.

The functional analysis approach described by Iwata et al. (1982/1994) has been used widely to determine the variables evoking and maintaining challenging behavior. However, one potential concern with conducting functional analyses is that repeated exposure to contingencies may induce a novel functional relation. To examine the likelihood of these potential iatrogenic effects, we evaluated social test conditions of the functional analysis for 116 participants and searched for patterns of responding indicative of acquisition. Patterns suggestive of acquisition occurred in 13.70% of tangible reinforcement conditions; however, the prevalence was only slightly lower in the attention condition (8.75%). Much lower prevalence was observed for the escape condition (2.13%). When grouped by quotient score, a pattern of acquisition was just as likely to be observed in the attention condition as in the tangible condition. Additionally, patterns indicative of acquisition were no more likely to be observed with participants who emitted automatically reinforced challenging behavior.

Further evidence of renewal in automatically maintained behavior.

Renewal is a relapse phenomenon that refers to the recurrence of a previously reduced behavior following a change in stimulus conditions. Muething et al. (2022) examined the phenomenology of renewal among individuals with automatically maintained challenging behavior treated at an outpatient clinic. We replicated their findings by retrospectively examining renewal across various topographies of automatically maintained behavior treated at an inpatient hospital, and we extended their work by also examining differences across subtypes of automatically maintained self-injurious behavior. The prevalence of renewal was comparable to that observed by Muething et al., supporting the notion that automatically maintained challenging behavior is susceptible to relapse phenomena. Furthermore, renewal was twice as likely to occur for individuals with Subtype 2 versus Subtype 1 self-injurious behavior, providing additional evidence of behavioral differentiation between subtypes. Our findings suggest that even after apparent stability in treatment, practitioners should remain vigilant for the recurrence of automatically maintained behavior during generalization.

Adolescent exposure to sucrose increases cocaine-mediated behaviours in adulthood via Smad3.

Adolescence, a critical period of developmental period, is marked by neurobiological changes influenced by environmental factors. Here, we show how exposure to sucrose, which is ubiquitously available in modern diets, results in changes in behavioural response to cocaine as an adult. Rats were given daily access to either 10% sucrose or water during the adolescent period (PND28-42). Following this period, rats are left undisturbed until they reach adulthood. In adulthood, rats were tested for (i) acquisition of a low dose of cocaine, (ii) progressive ratio (PR) test, and (iii) resistance to punished cocaine taking. Sucrose exposure resulted in significant alterations in all behavioural measures. To determine the neurobiological mechanisms leading to such behavioural adaptations, we find that adolescent sucrose exposure results in an upregulation of the transcription factor Smad3 in the nucleus accumbens (NAc) when compared with water-exposed controls. Transiently blocking the active form of this transcription factor (HSV-dnSmad3) during adolescence mitigated the enhanced cocaine vulnerability-like behaviours observed in adulthood. These findings suggest that prior exposure to sucrose during adolescence can heighten the reinforcing effects of cocaine. Furthermore, they identify the TGF-beta pathway and Smad3 as playing a key role in mediating enduring and long-lasting adaptations that contribute to sucrose-induced susceptibility to cocaine. Taken together, these results have important implications for development and suggest that adolescent sucrose exposure may persistently enhance the susceptibility to substance abuse.

A replication and extension of the augmented competing stimulus assessment.

Augmenting competing stimulus assessments by embedding tactics to increase stimulus engagement and disrupt challenging behavior can improve outcomes of treatments for automatically maintained self-injurious behavior, even for treatment-resistant subtypes. This study replicated and extended research on augmented competing stimulus assessments by reporting outcomes for 16 consecutively encountered cases with automatically maintained self-injurious behavior (19 total applications); six participants had treatment-responsive Subtype 1 and 10 had treatment-resistant Subtypes 2 or 3. Fewer high-competition stimuli were identified for individuals with treatment-resistant subtypes. When response-promotion and disruption tactics were applied and withdrawn, outcomes improved for six of eight applications. At least one high-competition stimulus was still effective when maintenance probes were conducted for a subset of participants. Ultimately, at least one high-competition stimulus was identified for each participant. Although augmenting tactics may not be necessary for all individuals, these findings provide additional support for their efficacy with treatment-resistant self-injurious behavior.

Simplified methods for identifying subtypes of automatically maintained self-injury.

Subtypes of automatically maintained self-injurious behavior (SIB) have been defined based on response patterns observed during the functional analysis, which are thought to reflect each subtype's distinct mechanisms. Current practice for identifying subtypes involves using structured criteria to identify whether SIB is automatically maintained, followed by the application of additional criteria to identify the subtype. We describe a series of studies directed at simplifying these methods to facilitate wider application of the subtyping model in research and practice. In Studies 1 and 2, we demonstrate the accuracy of modified criteria using the level of differentiation of SIB across the play and no-interaction conditions at distinguishing between two subtypes (i.e., Subtypes 1 and 2). We then demonstrate visual analysis (without structured criteria) can accurately identify SIB as automatically maintained in Study 3, which can be used in combination with level of differentiation to enable application of the subtyping model in practice.

Accumulated and distributed response-reinforcer arrangements during the treatment of escape-maintained problem behavior.

Contingent positive reinforcement has proven more effective in treating escape-maintained problem behavior than contingent negative reinforcement, particularly when problem behavior continues to produce escape. However, this research has overwhelmingly used distributed-reinforcement arrangements, where tasks and reinforcer access are interspersed throughout the work period. An alternative to interspersal involves allowing the individual to accumulate and then receive a larger quantity of reinforcement once work requirements are completed; this is known as an accumulated-reinforcement arrangement. The current study examined the efficacy of, and preference for positive (food) and negative (break) reinforcement contingencies delivered in accumulated and distributed arrangements in the treatment of escape-maintained problem behavior. In Experiment 1, accumulated break was preferred for 4 of 5 participants and accumulated food was preferred for 3 of 5. In Experiment 2, accumulated break was similarly effective to distributed break for 3 of 5 participants and accumulated and distributed food were equally effective for 4 participants.

Mask Compliance Training for Individuals With Intellectual and Developmental Disabilities.

Since the arrival of the novel coronavirus, recommendations for public masking have emerged to decrease infection rates. For a variety of reasons, tolerating wearing a mask is challenging for many individuals with intellectual and developmental disabilities (IDDs). Therefore, we evaluated behavioral strategies to promote compliance with wearing a mask with six hospitalized individuals diagnosed with IDDs. One participant was compliant with wearing the mask for extended durations during baseline while engaging in various activities (e.g., academics, leisure). For the other five individuals, engagement in activities alone was ineffective. Blocking mask removal, reinforcement for mask wearing, and noncontingent access to preferred activities or competing stimuli were then evaluated using a changing-criterion design in which the duration participants were required to tolerate the mask gradually increased. Increases in compliance with mask wearing were achieved with all participants; however, the terminal duration was attained for only four of the five individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40617-021-00583-7.

Initial outcomes of an augmented competing stimulus assessment.

Competing stimulus assessments (CSAs) are designed to identify stimuli that, when made freely available, reduce problem behavior. Although CSAs have demonstrated utility, identifying competing stimuli can be difficult for some individuals. The current study describes outcomes from an augmented CSA (A-CSA) for 6 consecutively encountered cases with treatment-resistant subtypes of automatically maintained problem behavior. When test stimuli were made freely available, only between 0 and 1 effective competing stimuli were identified for each case. Prompting and response blocking were temporarily employed in succession to promote engagement with stimuli and disrupt problem behavior. When those procedures were withdrawn and stimuli made freely available, the number of effective competing stimuli increased in all 6 cases. Findings suggest that procedures designed to promote engagement and disrupt problem behavior may allow the A-CSA to be a platform not only for identifying competing stimuli, but also for actively establishing competing stimuli.

Characteristics Associated with Autism Spectrum Disorder Risk in Individuals with Down Syndrome.

We examined autism spectrum disorder (ASD) risk in a large national sample of 203 individuals with Down syndrome, 6-25 years old, to determine the association of ASD risk with age, sex, IQ, adaptive behaviors, and maladaptive behaviors. We used a two-pronged approach by (1) considering ASD symptomatology continuously across the sample of individuals with DS and examining associations with each characteristic, and (2) dichotomizing our sample into high and low ASD risk groups and comparing groups on each characteristic. The pattern of results was largely similar across both types of analyses. ASD symptomatology/risk was negatively associated with IQ and adaptive behaviors and positively associated with certain types of maladaptive behaviors. Clinical implications for screening and therapeutic purposes are discussed.

Associations Between Medical History, Cognition, and Behavior in Youth With Down Syndrome: A Report From the Down Syndrome Cognition Project.

The cause of the high degree of variability in cognition and behavior among individuals with Down syndrome (DS) is unknown. We hypothesized that birth defects requiring surgery in the first years of life (congenital heart defects and gastrointestinal defects) might affect an individual's level of function. We used data from the first 234 individuals, age 6-25 years, enrolled in the Down Syndrome Cognition Project (DSCP) to test this hypothesis. Data were drawn from medical records, parent interviews, and a cognitive and behavior assessment battery. Results did not support our hypothesis. That is, we found no evidence that either birth defect was associated with poorer outcomes, adjusting for gender, race/ethnicity, and socioeconomic status. Implications for study design and measurement are discussed.

Does preference rank predict substitution for the reinforcer for problem behavior? a behavioral economic analysis.

Predictions made under low response requirements inherent in most preference assessments (PAs) do not guarantee the utility of stimuli in treatments. We examined whether PA rank would predict how well stimuli supported compliance for children with escape-maintained problem behavior by examining the relation between PA rank and demand elasticity across five fixed-ratio values. Three patterns were observed: All stimuli were selected equally across values, higher ranked stimuli were selected more at higher values, and something other than the highest ranked stimulus was selected more at higher values (i.e., mixed correspondence).

Additional free reinforcers increase persistence of problem behavior in a clinical context: A partial replication of laboratory findings.

Behavioral momentum theory is a quantitative framework used to characterize the persistence of behavior during response disruptors as a function of baseline stimulus-reinforcer relations. Results of several investigations have shown that alternative reinforcement can increase the resistance to change of a target response during extinction. In the present study, concomitant variable-interval fixed-time schedules of reinforcement for problem behavior were employed to simulate naturalistic situations involving the superimposition of response-independent reinforcers on a baseline schedule of reinforcement for problem behavior, as in the common use of noncontingent reinforcement treatments. Resistance to change of problem behavior was assessed during postsession periods of extinction by comparing response rates in extinction following sessions with and without additional reinforcer deliveries arranged by fixed-time schedules. For 2 out of 3 participants, problem behavior tended to be more resistant to extinction following periods in which additional fixed-time reinforcers were delivered. These results are discussed in terms of potential effects of noncontingent reinforcement on problem behavior when the intervention is discontinued or implemented without good treatment integrity.

Oral Ketorolac for Pain Relief During Intrauterine Device Insertion: A Double-Blinded Randomized Controlled Trial.

OBJECTIVE: To evaluate if oral ketorolac provides effective pain relief during placement of an IUD for contraception. METHODS: We conducted a double-blinded randomized controlled trial in a community hospital in Columbus, Ohio. Participants that met eligibility criteria were consented and randomized to receive either oral ketorolac 20 mg or placebo 40 to 60 minutes before IUD placement. Both participants and providers were blinded to the randomization group. The primary outcome was pain reduction (measured on a 0-10 numerical rating scale) during IUD placement. Data was analyzed using a two-sided independent samples t-test. An a priori sample size was calculated to detect a clinically meaningful difference of 2 points with 80% power. The type I error probability was α = 0.05. RESULTS: Seventy-two participants were enrolled and randomized between May 2014 until March 2016. Thirty-five in the ketorolac group and 36 in the placebo group were analyzed. There were no differences in baseline characteristics between participants or providers, as well as pain ratings prior to the procedure, at tenaculum placement, or at uterine sounding. There was a significant decrease in the pain of the ketorolac versus the placebo group rating at IUD deployment (4.2 vs. 5.7, P = 0.031), overall pain rating (3.6 vs. 4.9, P = 0.047), and pain 10 minutes after the procedure (1.1 vs, 2.5, P = 0.007). CONCLUSION: Oral ketorolac given 40 to 60 minutes prior to IUD insertion is effective in reducing pain during IUD deployment, overall pain, and pain 10 minutes after IUD placement.

Examining the reinforcing value of stimuli within social and non-social contexts in children with and without high-functioning autism.

One of the key diagnostic criteria for autism spectrum disorder includes impairments in social interactions. This study compared the extent to which boys with high-functioning autism and typically developing boys "value" engaging in activities with a parent or alone. Two different assessments that can empirically determine the relative reinforcing value of social and non-social stimuli were employed: paired-choice preference assessments and progressive-ratio schedules. There were no significant differences between boys with high-functioning autism and typically developing boys on either measure. Moreover, there was a strong correspondence in performance across these two measures for participants in each group. These results suggest that the relative reinforcing value of engaging in activities with a primary caregiver is not diminished for children with autism spectrum disorder.

A quantitative review of overjustification effects in persons with intellectual and developmental disabilities.

The overjustification hypothesis suggests that extrinsic rewards undermine intrinsic motivation. Extrinsic rewards are common in strengthening behavior in persons with intellectual and developmental disabilities; we examined overjustification effects in this context. A literature search yielded 65 data sets permitting comparison of responding during an initial no-reinforcement phase to a subsequent no-reinforcement phase, separated by a reinforcement phase. We used effect sizes to compare response levels in these two no-reinforcement phases. Overall, the mean effect size did not differ from zero; levels in the second no-reinforcement phase were equally likely to be higher or lower than in the first. However, in contrast to the overjustification hypothesis, levels were higher in the second no-reinforcement phase when comparing the single no-reinforcement sessions immediately before and after reinforcement. Outcomes consistent with the overjustification hypothesis were somewhat more likely when the target behavior occurred at relatively higher levels prior to reinforcement.

Effects of signaled and unsignaled alternative reinforcement on persistence and relapse in children and pigeons.

Three experiments explored the impact of different reinforcer rates for alternative behavior (DRA) on the suppression and post-DRA relapse of target behavior, and the persistence of alternative behavior. All experiments arranged baseline, intervention with extinction of target behavior concurrently with DRA, and post-treatment tests of resurgence or reinstatement, in two- or three-component multiple schedules. Experiment 1, with pigeons, arranged high or low baseline reinforcer rates; both rich and lean DRA schedules reduced target behavior to low levels. When DRA was discontinued, the magnitude of relapse depended on both baseline reinforcer rate and the rate of DRA. Experiment 2, with children exhibiting problem behaviors, arranged an intermediate baseline reinforcer rate and rich or lean signaled DRA. During treatment, both rich and lean DRA rapidly reduced problem behavior to low levels, but post-treatment relapse was generally greater in the DRA-rich than the DRA-lean component. Experiment 3, with pigeons, repeated the low-baseline condition of Experiment 1 with signaled DRA as in Experiment 2. Target behavior decreased to intermediate levels in both DRA-rich and DRA-lean components. Relapse, when it occurred, was directly related to DRA reinforcer rate as in Experiment 2. The post-treatment persistence of alternative behavior was greater in the DRA-rich component in Experiment 1, whereas it was the same or greater in the signaled-DRA-lean component in Experiments 2 and 3. Thus, infrequent signaled DRA may be optimal for effective clinical treatment.

Copy Number Variants Associated with 14 Cases of Self-Injurious Behavior.

Copy number variants (CNVs) were detected and analyzed in 14 probands with autism and intellectual disability with self-injurious behavior (SIB) resulting in tissue damage. For each proband we obtained a clinical history and detailed behavioral descriptions. Genetic anomalies were observed in all probands, and likely clinical significance could be established in four cases. This included two cases having novel, de novo copy number variants and two cases having variants likely to have functional significance. These cases included segmental trisomy 14, segmental monosomy 21, and variants predicted to disrupt the function of ZEB2 (encoding a transcription factor) and HTR2C (encoding a serotonin receptor). Our results identify variants in regions previously implicated in intellectual disability and suggest candidate genes that could contribute to the etiology of SIB.

REDUCING AMBIGUITY IN THE FUNCTIONAL ASSESSMENT OF PROBLEM BEHAVIOR.

Severe problem behavior (e.g., self-injury and aggression) remains among the most serious challenges for the habilitation of persons with intellectual disabilities and is a significant obstacle to community integration. The current standard of behavior analytic treatment for problem behavior in this population consists of a functional assessment and treatment model. Within that model, the first step is to assess the behavior-environment relations that give rise to and maintain problem behavior, a functional behavioral assessment. Conventional methods of assessing behavioral function include indirect, descriptive, and experimental assessments of problem behavior. Clinical investigators have produced a rich literature demonstrating the relative effectiveness for each method, but in clinical practice, each can produce ambiguous or difficult-to-interpret outcomes that may impede treatment development. This paper outlines potential sources of variability in assessment outcomes and then reviews the evidence on strategies for avoiding ambiguous outcomes and/or clarifying initially ambiguous results. The end result for each assessment method is a set of best practice guidelines, given the available evidence, for conducting the initial assessment.

Distributed and accumulated reinforcement arrangements: evaluations of efficacy and preference.

We assessed the efficacy of, and preference for, accumulated access to reinforcers, which allows uninterrupted engagement with the reinforcers but imposes an inherent delay required to first complete the task. Experiment 1 compared rates of task completion in 4 individuals who had been diagnosed with intellectual disabilities when reinforcement was distributed (i.e., 30-s access to the reinforcer delivered immediately after each response) and accumulated (i.e., 5-min access to the reinforcer after completion of multiple consecutive responses). Accumulated reinforcement produced response rates that equaled or exceeded rates during distributed reinforcement for 3 participants. Experiment 2 used a concurrent-chains schedule to examine preferences for each arrangement. All participants preferred delayed, accumulated access when the reinforcer was an activity. Three participants also preferred accumulated access to edible reinforcers. The collective results suggest that, despite the inherent delay, accumulated reinforcement is just as effective and is often preferred by learners over distributed reinforcement.