Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Learning categories via rules and similarity: comparing adults and children.

Two experiments explored the different strategies used by children and adults when learning new perceptual categories. Participants were asked to learn a set of categories for which both a single-feature rule and overall similarity would allow for perfect performance. Other rules allowed for suboptimal performance. Transfer stimuli (Experiments 1 and 2) and single features (Experiment 2) were presented after training to help determine how the categories were learned. In both experiments, we found that adults made significantly more optimal rule-based responses to the test stimuli than children. Children showed a variety of categorization styles, with a few relying on the optimal rules, many relying on suboptimal single-feature rules, and only a few relying on overall family resemblance. We interpret these results within a multiple systems framework, and we argue that children show the pattern they do because they lack the necessary cognitive resources to fully engage in hypothesis testing, rule selection, and verbally mediated category learning.

Continuous executive function disruption interferes with application of an information integration categorization strategy.

Category learning is often characterized as being supported by two separate learning systems. A verbal system learns rule-defined (RD) categories that can be described using a verbal rule and relies on executive functions (EFs) to learn via hypothesis testing. A nonverbal system learns non-rule-defined (NRD) categories that cannot be described by a verbal rule and uses automatic, procedural learning. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of EFs, but recent studies suggest that EFs may play a role in the nonverbal system-specifically, to facilitate the transition away from the verbal system. Accordingly, continuously interfering with EFs during the categorization process, so that EFs are never fully available to facilitate the transition, may be more detrimental to the nonverbal system than is temporary EF interference. Participants learned an NRD or an RD category while EFs were untaxed, taxed temporarily, or taxed continuously. When EFs were continuously taxed during NRD categorization, participants were less likely to use a nonverbal categorization strategy than when EFs were temporarily taxed, suggesting that when EFs were unavailable, the transition to the nonverbal system was hindered. For the verbal system, temporary and continuous interference had similar effects on categorization performance and on strategy use, illustrating that EFs play an important but different role in each of the category-learning systems.

Perceptual fluency can be used as a cue for categorization decisions.

Learning in the prototype distortion task is thought to involve perceptual learning in which category members experience an enhanced visual response (Ashby & Maddox. Annual Review of Psychology, 56, 149-178, 2005). This response likely leads to more-efficient processing, which in turn may result in a feeling of perceptual fluency for category members. We examined the perceptual-fluency hypothesis by manipulating fluency independently from category membership. We predicted that when perceptual fluency was induced using subliminal priming, this fluency would be misattributed to category membership and would affect categorization decisions. In a prototype distortion task, the participants were more likely to judge stimuli that were not members of the category as category members when the nonmembers were made perceptually fluent with a matching subliminal prime. This result suggests that perceptual fluency can be used as a cue during some categorization decisions. In addition, the results provided converging evidence that some types of categorization are based on perceptual learning.

The effects of concurrent verbal and visual tasks on category learning.

Current theories of category learning posit separate verbal and nonverbal learning systems. Past research suggests that the verbal system relies on verbal working memory and executive functioning and learns rule-defined categories; the nonverbal system does not rely on verbal working memory and learns non-rule-defined categories (E. M. Waldron & F. G. Ashby, 2001; D. Zeithamova & W. T. Maddox, 2006). However, relatively little research has explored the importance of visual working memory or visual processing for either system. The authors investigated the role of working memory (Experiment 1a and 1b), visual processing (Experiment 2), and executive functioning for each system, using a concurrent task methodology. It was found that visual tasks with high executive functioning demands and verbal tasks with high or low executive demands disrupted rule-defined learning, whereas any visual task, regardless of executive functioning demand, disrupted non-rule-defined learning. Taken together, these results confirm the importance of verbal working memory and executive functioning for the verbal system and provide new evidence for the importance of visual processing for the nonverbal system. These results help to clarify understanding of the nonverbal system and have implications for multiple systems theories of category learning (F. G. Ashby, L. A. Alfonso-Reese, A. U. Turken, & E. M. Waldron, 1998).