Reactivation of single-episode pain patterns in the hippocampus and decision making

Aversive and rewarding experiences can exert a strong influence on subsequent behavior. While decisions are often supported by the value of single past episodes, most research has focused on the role of well-learned value associations. Recent studies have begun to investigate the influence of reward-associated episodes, but it is unclear if these results generalize to negative experiences such as pain. To investigate whether and how the value of previous aversive experiences modulates behavior and brain activity, in our experiments female and male human participants experienced episodes of high or low pain in conjunction with incidental, trial-unique neutral pictures. In an incentive-compatible surprise test phase, we found that participants avoided pain-paired objects. In a separate fMRI experiment, at test, participants exhibited significant pain value memory. Neurally, when participants were re-exposed to pain-paired objects, we found no evidence for reactivation of pain-related patterns in pain-responsive regions such as the anterior insula. Critically, however, we found significant reactivation of pain-related patterns of activity in the hippocampus, such that activity significantly discriminated high versus low pain episodes. Further, stronger reactivation in the anterior hippocampus was related to improved pain value memory performance. Our results demonstrate that single incidental aversive experiences can build memories that affect decision making and that this influence may be supported by the hippocampus

Reward learning and working memory: Effects of massed versus spaced training and post-learning delay period

Neuroscience research has illuminated the mechanisms supporting learning from reward feedback, demonstrating a critical role for the striatum and midbrain dopamine system. However, in humans, short-term working memory that is dependent on frontal and parietal cortices can also play an important role, particularly in commonly used paradigms in which learning is relatively condensed in time. Given the growing use of reward-based learning tasks in translational studies in computational psychiatry, it is important to understand the extent of the influence of working memory and also how core gradual learning mechanisms can be better isolated. In our experiments, we manipulated the spacing between repetitions along with a post-learning delay preceding a test phase. We found that learning was slower for stimuli repeated after a long delay (spaced-trained) compared to those repeated immediately (massed-trained), likely reflecting the remaining contribution of feedback learning mechanisms when working memory is not available. For massed learning, brief interruptions led to drops in subsequent performance, and individual differences in working memory capacity positively correlated with overall performance. Interestingly, when tested after a delay period but not immediately, relative preferences decayed in the massed condition and increased in the spaced condition. Our results provide additional support for a large role of working memory in reward-based learning in temporally condensed designs. We suggest that spacing training within or between sessions is a promising approach to better isolate and understand mechanisms supporting gradual reward-based learning, with particular importance for understanding potential learning dysfunctions in addiction and psychiatric disorders

Learning of distant state predictions by the orbitofrontal cortex in humans

Representations of our future environment are essential for planning and decision making. Previous research in humans has demonstrated that the hippocampus is a critical region for forming and retrieving associations, while the medial orbitofrontal cortex (OFC) is an important region for representing information about recent states. However, it is not clear how the brain acquires predictive representations during goal-directed learning. Here, we show using fMRI that while participants learned to find rewards in multiple different Y-maze environments, hippocampal activity was highest during initial exposure and then decayed across the remaining repetitions of each maze, consistent with a role in rapid encoding. Importantly, multivariate patterns in the OFC-VPFC came to represent predictive information about upcoming states approximately 30 s in the future. Our findings provide a mechanism by which the brain can build models of the world that span long-timescales to make predictions

Retroactive and graded prioritization of memory by reward

Many decisions are based on an internal model of the world. Yet, how such a model is constructed from experience and represented in memory remains unknown. We test the hypothesis that reward shapes memory for sequences of events by retroactively prioritizing memory for objects as a function of their distance from reward. Human participants encountered neutral objects while exploring a series of mazes for reward. Across six data sets, we find that reward systematically modulates memory for neutral objects, retroactively prioritizing memory for objects closest to the reward. This effect of reward on memory emerges only after a 24-hour delay and is stronger for mazes followed by a longer rest interval, suggesting a role for post-reward replay and overnight consolidation, as predicted by neurobiological data in animals. These findings demonstrate that reward retroactively prioritizes memory along a sequential gradient, consistent with the role of memory in supporting adaptive decision-making

Reinstated episodic context guides sampling-based decisions for reward.

How does experience inform decisions? In episodic sampling, decisions are guided by a few episodic memories of past choices. This process can yield choice patterns similar to model-free reinforcement learning; however, samples can vary from trial to trial, causing decisions to vary. Here we show that context retrieved during episodic sampling can cause choice behavior to deviate sharply from the predictions of reinforcement learning. Specifically, we show that, when a given memory is sampled, choices (in the present) are influenced by the properties of other decisions made in the same context as the sampled event. This effect is mediated by fMRI measures of context retrieval on each trial, suggesting a mechanism whereby cues trigger retrieval of context, which then triggers retrieval of other decisions from that context. This result establishes a new avenue by which experience can guide choice and, as such, has broad implications for the study of decisions

A road to reality with topological superconductors

Topological states of matter are a source of low-energy quasiparticles, bound to a defect or propagating along the surface. In a superconductor these are Majorana fermions, described by a real rather than a complex wave function. The absence of complex phase factors promises protection against decoherence in quantum computations based on topological superconductivity. This is a tutorial style introduction written for a Nature Physics focus issue on topological matter.Comment: pre-copy-editing, author-produced version of the published paper: 4 pages, 2 figure

The ethics of synthetic biology research and development:a principlist approach

A principlist approach is adopted to analyse the ethical status of synthetic biology (synbio) research and development. The principle of nonmaleficence generates precaution-driven conclusions that are excessively restrictive to the field of synbio. The principle of beneficence is best served by permitting synbio research to flourish and not have it treated as a special case warranting the imposition of a high degree of external and self-regulation. Synbio may offend the principle of justice in certain circumstances; however, such issues are largely restricted to the initial stages of synbio innovation, whilst in the longer term the development of the field can be expected to promote just ends. The principle of respect for autonomy entails that scientists ought to be afforded a broad scope to freely pursue synbio research and development in a curiosity-driven fashion. In balancing the various conclusions under the four principles, the author concludes that society has an ethical obligation to support the development of synbio research and development and not restrict this important nascent field by the imposition of stern regulation

Pleurotomy with subxyphoid pleural drain affords similar effects to pleural integrity in pulmonary function after off-pump coronary artery bypass graft

Background: Exacerbation of pulmonary dysfunction has been reported in patients receiving a pleural drain inserted through the intercostal space in comparison to patients with an intact pleura undergoing coronary artery bypass grafting (CABG). Evidence suggests that shifting the site of pleural drain insertion to the subxyphoid position minimizes chest wall trauma and preserves respiratory function in the early postoperative period. the aim of this study was to compare the pulmonary function parameters, clinical outcomes, and pain score between patients undergoing pleurotomy with pleural drain placed in the subxyphoid position and patients with intact pleural cavity after off-pump CABG (OPCAB) using left internal thoracic artery (LITA).Methods: Seventy-one patients were allocated into two groups: I (n = 38 open left pleural cavity and pleural drain inserted in the subxyphoid position); II (n = 33 intact pleural cavity). Pulmonary function tests and clinical parameters were recorded preoperatively and on postoperative days (POD) 1, 3 and 5. Arterial blood gas analysis and shunt fraction were evaluated preoperatively and in POD1. Pain score was assessed on POD1. To monitor pleural effusion and atelectasis chest radiography was performed routinely 1 day before operation and until POD5.Results: in both groups a significant impairment was found in lung function parameters until on POD5. However, no significant difference in forced vital capacity and forced expiratory volume in 1 second were seen between groups. A significant decrease in partial pressure of arterial oxygen and an increase in shunt fraction values were observed on POD1 in both groups, but no statistical difference was found when the groups were compared. Pleural effusion and atelectasis until on POD5 were similar in both groups. There were no statistical differences in pain score, duration of mechanical ventilation and postoperative hospital stay between groups.Conclusion: Subxyphoid insertion of pleural drain provides similar effects to preserved pleural integrity in pulmonary function, clinical outcomes, and thoracic pain after OPCAB. Therefore, our results support the hypothesis that once pleural cavities are incidentally or purposely opened during LITA dissection, subxyphoid placement of the pleural drain is recommended.Universidade Federal de São Paulo, Escola Paulista Med, Pirajussara Hosp, Dept Med,Cardiol Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo Hosp, Dept Med,Cardiol Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Physiotherapy Sch, Dept Human Movement Sci, BR-11060001 Santos, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo Hosp, Dept Med,Pneumol Discipline, BR-04039002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Pirajussara Hosp, Dept Med,Cardiovasc Surg Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo Hosp, Dept Med,Cardiovasc Surg Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Pirajussara Hosp, Dept Med,Cardiol Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo Hosp, Dept Med,Cardiol Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Physiotherapy Sch, Dept Human Movement Sci, BR-11060001 Santos, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo Hosp, Dept Med,Pneumol Discipline, BR-04039002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Pirajussara Hosp, Dept Med,Cardiovasc Surg Discipline, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo Hosp, Dept Med,Cardiovasc Surg Discipline, BR-04024002 São Paulo, BrazilWeb of Scienc

Prioritized memory access explains planning and hippocampal replay.

To make decisions, animals must evaluate candidate choices by accessing memories of relevant experiences. Yet little is known about which experiences are considered or ignored during deliberation, which ultimately governs choice. We propose a normative theory predicting which memories should be accessed at each moment to optimize future decisions. Using nonlocal 'replay' of spatial locations in hippocampus as a window into memory access, we simulate a spatial navigation task in which an agent accesses memories of locations sequentially, ordered by utility: how much extra reward would be earned due to better choices. This prioritization balances two desiderata: the need to evaluate imminent choices versus the gain from propagating newly encountered information to preceding locations. Our theory offers a simple explanation for numerous findings about place cells; unifies seemingly disparate proposed functions of replay including planning, learning, and consolidation; and posits a mechanism whose dysfunction may underlie pathologies like rumination and craving