The persistence of operant responding in the context of distractors and opposing forces is of central importance to the success of behavioral interventions. It has been successfully analyzed with ...Behavioral Momentum Theory. Key data from the research inspired by that theory are reanalyzed in terms of more molecular behavioral mechanisms: the demotivational effects of disruptors, and their differential impacts on the target response and other responses that interact with them. Behavioral momentum is regrounded as a nonlinear effect of motivation and reinforcement rate on response probability and persistence. When response probabilities are high, more energy is required to further increase or to decrease them than when they are low. Classic Behavioral Momentum Theory effects are reproduced with this account. Finally, it is shown how the new account involving motivation and competition is closely related to the metaphor of force and action that is at the core of Behavioral Momentum Theory.
We propose quantitative experimental approaches to the question of whether positive and negative reinforcement are functionally different, and discuss scientific and ethical concerns that would arise ...if these approaches were pursued.
If a selective serotonin-reuptake inhibitor was felt to be indicated by the treating neurologist, participants would have needed to stop the study drug, raising challenging ethical and practical ...issues for both participants and trial viability. ...the well established efficacy of selective serotonin-reuptake inhibitors in treating mood disorder (symptomatic treatment) that can consequently enable people with secondary progressive multiple sclerosis to better engage in rehabilitative or neurorestorative programmes. ...a point that we cautiously discussed, is whether fluoxetine has any degree of anti-inflammatory effect, as shown by the reduction in new or enlarging T2 lesions (adjusted rate ratio of fluoxetine vs placebo 0·5 95% CI 0·3–0·9; p=0·012).1 This question would need to be pursued again in an inflammatory MRI paradigm applied to an appropriately selected trial population with relevant outcomes.
Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long‐term functional communication training (FCT). During FCT, the children ...completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently throughout FCT, extinction probes were conducted within a withdrawal design in which task completion, manding, and destructive behavior were placed on extinction to evaluate the relative persistence of appropriate and destructive behavior over the course of treatment. FCT continued until appropriate behavior persisted and destructive behavior failed to recur at baseline levels during extinction probes. The completion of FCT was followed by four challenges to the persistence of treatment effects conducted within mixed‐ or multiple‐schedule designs: (a) extended extinction sessions (from 5 to 15 min), (b) introduction of a novel task, (c) removal of the microswitch and communication card, and (d) a mixed schedule of reinforcement in which both appropriate and destructive behavior produced reinforcement. The results showed that although FCT often resulted in quick reductions in destructive behavior and increases in appropriate behavior, destructive behavior often recurred during the extinction probes conducted during the initial treatment. When the effects of treatment persisted during the extinction probes, the remaining challenges to treatment effects resulted in only mild to moderate disruptions in behavior. These results are consistent with the quantitative predictions of behavioral momentum theory and may provide an alternative definition of maintenance as constituting behavioral persistence.
To evaluate an updated algorithm in the detection of urinary tract infection (UTI) prior to high-dose corticosteroid treatment in acute relapses in multiple sclerosis (MS). This updated algorithm ...aimed to decrease the unnecessary use of antibiotics, whilst maintaining accuracy and safety.
Prospective cohort study of 471 consecutive patients with MS relapses in a hospital-based outpatient acute relapse clinic. 172 patients met exclusion criteria, leaving 299 patients for analysis. Patients underwent urine dipstick and were treated for UTI if 2 or more of: nitrites, leukocyte esterase and cloudy urine were positive. Patients with confirmed acute MS relapse were treated with high dose intravenous or oral methylprednisolone.
Significant bacteriuria (>105 colony forming units/mL) was present in 33 (11%, 95% CI 8-15) patients. The algorithm sensitivity and specificity was 24% and 94% respectively; the negative predictive value was 91%. The overall accuracy of the algorithm was 87%. No adverse sequelae were identified in 25 patients who received high dose methylprednisolone in the presence of an untreated UTI.
With an improved specificity, this updated algorithm addresses previous issues concerning the unnecessary prescription of antibiotics, whilst improving accuracy and maintaining safety.
•High dose steroids to treat acute MS relapses may be delayed when UTI is suspected.•Accurate urine screening allows early treatment and reduces unnecessary antibiotics.•≥2/3 of positive nitrites, leukocyte esterase and cloudy urine gives 87% accuracy.•Risks of high dose steroids when bacteriuria is present remains to be established.
There is a growing interest in the topography of brain regions associated with disorders of consciousness. This has caused increased research output, yielding many publications investigating the ...topic with varying methodologies. The objective of this study was to ascertain the topographical regions of the brain most frequently associated with disorders of consciousness.
We performed a cross-sectional text-mining analysis of disorders of consciousness studies. A text mining algorithm built in the Python programming language searched documents for anatomical brain terminology. We reviewed primary PubMed studies between January 1st 2000 to 8th February 2023 for the search query "Disorders of Consciousness." The frequency of brain regions mentioned in these articles was recorded, ranked, then built into a graphical network. Subgroup analysis was performed by evaluating the impact on our results if analyses were based on abstracts, full-texts, or topic-modeled groups (non-negative matrix factorization was used to create subgroups of each collection based on their key topics). Brain terms were ranked by their frequency and concordance was measured between subgroups. Graphical analysis was performed to explore relationships between the anatomical regions mentioned. The PageRank algorithm (used by Google to list search results in order of relevance) was used to determine global importance of the regions.
The PubMed search yielded 24,944 abstracts and 3,780 full texts. The topic-modeled subgroups contained 2015 abstracts and 283 full texts. Text Mining across all document groups concordantly ranked the thalamus the highest (Savage score = 11.716), followed by the precuneus (Savage score = 4.983), hippocampus (Savage score = 4.483). Graphical analysis had 5 clusters with the thalamus once again having the highest PageRank score (PageRank = 0.0344).
The thalamus, precuneus and cingulate cortex are strongly associated with disorders of consciousness, likely due to the roles they play in maintaining awareness and involvement in the default mode network, respectively. The findings also suggest that other areas of the brain like the cerebellum, cuneus, amygdala and hippocampus also share connections to consciousness should be further investigated.
In the metaphor of behavioral momentum, the rate of a free operant in the presence of a discriminative stimulus is analogous to the velocity of a moving body, and resistance to change measures an ...aspect of behavior that is analogous to its inertial mass. An extension of the metaphor suggests that preference measures an analog to the gravitational mass of that body. The independent functions relating resistance to change and preference to the conditions of reinforcement may be construed as convergent measures of a single construct, analogous to physical mass, that represents the effects of a history of exposure to the signaled conditions of reinforcement and that unifies the traditionally separate notions of the strength of learning and the value of incentives. Research guided by the momentum metaphor encompasses the effects of reinforcement on response rate, resistance to change, and preference and has implications for clinical interventions, drug addiction, and self-control. In addition, its principles can be seen as a modern, quantitative version of Thorndike's (1911) Law of Effect, providing a new perspective on some of the challenges to his postulation of strengthening by reinforcement.
Slower than planned recruitment is a major factor contributing to the delay or failure of randomised controlled trials to report on time. There is a limited evidence base regarding the optimisation ...of recruitment strategies. Here we performed an observational review of our experience in recruitment for two large randomised controlled trials for people with secondary progressive multiple sclerosis. We aimed to explicitly determine those factors which can facilitate trial recruitment in progressive neurodegenerative disease.
Recruitment data from the sequential MS-SMART NCT01910259 and MS-STAT2 NCT03387670 UK randomised controlled trials was reviewed from the largest recruiting site, University College London (UCL). The trial population was similar which allowed comparison over the two recruitment periods of 2015-2016 and 2018-2021. This included sources of referral, progress through stages of recruitment, reasons for participant ineligibility and the impact of publicity events upon recruitment.
In MS-SMART, 18% of patients contacted were enrolled, compared to 27% for MS-STAT2. Online registration of interest portals provided the greatest number of referrals (76% in MS-SMART, and 51% in MS-STAT2), with publicity in national media outlets producing a demonstrable increase in the number of potential participants. The introduction of an online self-screening questionnaire for MS-STAT2 resulted in 67% of potential participants (3080 of 4605) automatically determining their own ineligibility. In both studies, however, around 60% of those directly telephoned to discuss the study were not eligible, with difficulties related to travel to trial visits, or excluded medication, being the most common issues. Eighty-four percent of those deemed potentially eligible following telephone calls were enrolled in the MS-STAT2 study, compared to only 55% for MS-SMART.
Through a detailed review of recruiting participants at the largest centre into two large randomised controlled trials with similar entry criteria, we have identified a number of approaches that may improve recruitment efficiency. We highlight here the importance of mandatory online self-screening questionnaires, a coordinated publicity campaign, and simple interventions such as eligibility checklists and appointment reminders. Recruitment approaches should be further assessed through a studies within a trial (SWAT) design.
MS-SMART: NCT01910259 ; registered July 2013 and MS-STAT2: NCT03387670 ; registered Jan 2018.
Maintenance and generalization have been inconsistently defined in the behavior analytic literature. The term treatment relapse is used commonly in the medical and mental health literature to refer ...to the return of a condition that was previously considered successfully treated. Basic behavioral researchers have studied relapse related to behavioral momentum theory (BMT). The present authors discuss the differences in terminology and propose the field adopt the term treatment relapse when treatments are no longer effective or when their effects are not present in settings in which the treatment was not originally implemented. The implications BMT has for designing behavioral interventions to minimize or avoid treatment relapse are discussed along with a brief review of applied studies that demonstrate BMT may be useful for practitioners and applied researchers.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionThe major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network ...(CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist).Methods and analysisPatients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland.Ethics and disseminationMS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numbers NCT01910259; 2012-005394-31; ISRCTN28440672.
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