The Nucleus Accumbens and Pavlovian Reward Learning

The ability to form associations between predictive environmental events and rewarding outcomes is a fundamental aspect of learned behavior. This apparently simple ability likely requires complex neural processing evolved to identify, seek, and utilize natural rewards and redirect these activities based on updated sensory information. Emerging evidence from both animal and human research suggests that this type of processing is mediated in part by the nucleus accumbens and a closely associated network of brain structures. The nucleus accumbens is required for a number of reward-related behaviors, and processes specific information about reward availability, value, and context. Additionally, this structure is critical for the acquisition and expression of most Pavlovian stimulus-reward relationships, and cues that predict rewards produce robust changes in neural activity in the nucleus accumbens. While processing within the nucleus accumbens may enable or promote Pavlovian reward learning in natural situations, it has also been implicated in aspects of human drug addiction, including the ability of drug-paired cues to control behavior. This article will provide a critical review of the existing animal and human literature concerning the role of the NAc in Pavlovian learning with non-drug rewards and consider some clinical implications of these findings

Nucleus accumbens neurons encode predicted and ongoing reward costs in rats

Efficient decision making requires that animals consider both the benefits and costs of potential actions, such as the amount of effort or temporal delay involved in reward seeking. The nucleus accumbens (NAc) has been implicated in the ability to choose between options with different costs and overcome high costs when necessary, but it is not clear how NAc processing contributes to this role. Here, neuronal activity in the NAc was monitored using multi-neuron electrophysiology during two cost-based decision tasks in which either reward effort or reward delay was manipulated. In each task, distinct visual cues predicted high value (low effort/immediate) and low value (high effort/delayed) rewards. After training, animals exhibited a behavioral preference for high value rewards, yet overcame high costs when necessary to obtain rewards. Electrophysiological analysis indicated that a subgroup of NAc neurons exhibited phasic increases in firing rate during cue presentations. In the effort-based decision task (but not the delay-based task), this population reflected the cost-discounted value of the future response. In contrast, other subgroups of cells were activated during response initiation or reward delivery, but activity did not differ on the basis of reward cost. Finally, another population of cells exhibited sustained changes in firing rate while animals completed high effort requirements or waited for delayed rewards. These findings are consistent with previous reports that implicate NAc function in reward prediction and behavioral allocation during reward-seeking behavior, and suggest a mechanism by which NAc activity contributes to both cost-based decisions and actual cost expenditure

Phasic Nucleus Accumbens Dopamine Encodes Risk-Based Decision-Making Behavior

To optimize behavior organisms evaluate the risks and benefits of available choices. The mesolimbic dopamine (DA) system encodes information about response costs and reward delays that bias choices. However, it remains unclear whether subjective value associated with risk-taking behavior is encoded by DA release

Phasic Nucleus Accumbens Dopamine Release Encodes Effort- and Delay-Related Costs

Optimal decision making requires that organisms correctly evaluate both the costs and benefits of potential choices. Dopamine transmission within the nucleus accumbens (NAc) has been heavily implicated in reward learning and decision making, but it is unclear how dopamine release may contribute to decisions that involve costs

Thinking Through our Processes: How the UCSC Community Psychology Research & Action Team Strives to Embody Ethical, Critically Reflexive Anti-racist Feminist Praxis

Co-written by eight people, this paper describes how the UCSC Community Psychology Research and Action Team (CPRAT) organizes itself in weekly group meetings and how this structure is an attempt to embody an ethical, critically reflexive anti-racist feminist praxis. First, we outline the community psychology core competency of an ethical, reflective practice (Dalton & Wolfe, 2012). We offer a friendly amendment to consider an ethical, critically reflexive anti-racist feminist praxis. Second, we discuss how we organize CPRAT meetings to uphold these ideas. We describe our current structure, which includes personal and project check-ins, rotating facilitation, and attention to broader professional development issues. Third, we provide two examples to illustrate our process: (a) why talking about poop matters in addressing imposter syndrome and (b) getting our team on the same page regarding a research site. We end the paper with a description of a “rough edge,” or an area for growth in our praxis

Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer

The risk factors and potential practice implications of radiation-induced pleural effusion (RIPE) are undefined. This study examined lung cancer patients treated with thoracic radiation therapy (TRT) having follow-up computed tomography (CT) or 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Increased volumes of pleural effusion after TRT without evidence of tumor progression was considered RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5-55 Gy (V5-V55) and mean lung dose (MLD) were analyzed by receiver operating characteristic analysis. Clinical and treatment-related risk factors were detected by univariate and multivariate analyses. 175 out of 806 patients receiving TRT with post-treatment imaging were included. 51 patients (24.9%) developed RIPE; 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and dyspnea (35.3%). Female (OR = 0.380, 95% CI: 0.156–0.926, p = 0.033) and Caucasian race (OR = 3.519, 95% CI: 1.327–9.336, p = 0.011) were significantly associated with lower risk of RIPE. Stage and concurrent chemotherapy had borderline significance (OR = 1.665, p = 0.069 and OR = 2.580, p = 0.080, respectively) for RIPE. Patients with RIPE had significantly higher whole lung V5-V40, V50 and MLD. V5 remained as a significant predictive factor for RIPE and symptomatic RIPE (p = 0.007 and 0.022) after adjusting for race, gender and histology. To include, the incidence of RIPE is notable. Whole lung V5 appeared to be the most significant independent risk factor for symptomatic RIPE

Regional specificity in the real-time development of phasic dopamine transmission patterns during acquisition of a cue-cocaine association in rats

Drug seeking is significantly regulated by drug-associated cues and associative learning between environmental cues and cocaine reward is mediated by dopamine transmission within the nucleus accumbens (NAc). However, dopamine transmission during early acquisition of a cue-cocaine association has never been assessed because of the technical difficulties associated with resolving cue-evoked and cocaine-evoked dopamine release within the same conditioning trial. Here, we used fast-scan cyclic voltammetry to measure sub-second fluctuations in dopamine concentration within the NAc core and shell during the initial acquisition of a cue-cocaine Pavlovian association. Within the NAc core, cue-evoked dopamine release developed during conditioning. However, within the NAc shell, the predictive cue appeared to cause an unconditioned decrease in dopamine concentration. The pharmacological effects of cocaine also differed between sub-regions, as cocaine increased phasic dopamine release events within the NAc shell but not the core. Thus, real-time measurements not only revealed the initial development of a conditioned neurochemical response but also demonstrated differential phasic dopamine transmission patterns across NAc sub-regions during the acquisition of a cue-cocaine association

A Partial Response to Reintroduced Chemotherapy in a Resistant Small Cell Lung Cancer Patient after Priming with RRx-001

As an exceedingly recalcitrant and highly aggressive tumor type without Food and Drug Administration-approved treatment or a known cure, the prognosis of recurrent extensive stage platinum-resistant/refractory small cell lung cancer (SCLC) is worse than other types of lung cancer, and many other tumor types, given a response rate of less than 10% and an overall survival of less than six months. It was broadly classified into three groups based on the initial response to cisplatin/etoposide therapy, platinum-refractory, platinum-resistant, and platinum-sensitive, extensive stage SCLC inevitably relapses, at which point the only standard options are to rechallenge with the first-line chemotherapeutic regimen in the case of sensitive disease or to start the topoisomerase I inhibitor, topotecan. Sensitive disease is defined by a response to the first-line therapy and a treatment-free interval of at least 90 days, while the definitions of refractory and resistant disease, respectively, are nonresponse to the first-line treatment or relapse within 90 days. As an important predictor of response to the second-line treatment, the clinical cutoff of three months (or two months in some cases) for resistant and sensitive disease, which along with performance status prognostically separates patients into high- and low-risk categories, dictates subsequent management. This case report presents a resistant SCLC patient enrolled on a Phase II clinical trial called QUADRUPLE THREAT (formerly TRIPLE THREAT, NCT02489903) who responded to reintroduced platinum doublets after sequential priming with the resistance-reversing epi-immunotherapeutic agent, RRx-001. In the QUADRUPLE THREAT clinical trial, both during priming with RRx-001 and during sequential treatment with platinum doublets, the patient maintained a good quality of life and performance status.Peer reviewe