Hierarchical control over effortful behavior by rodent medial frontal cortex : a computational model

The anterior cingulate cortex (ACC) has been the focus of intense research interest in recent years. Although separate theories relate ACC function variously to conflict monitoring, reward processing, action selection, decision making, and more, damage to the ACC mostly spares performance on tasks that exercise these functions, indicating that they are not in fact unique to the ACC. Further, most theories do not address the most salient consequence of ACC damage: impoverished action generation in the presence of normal motor ability. In this study we develop a computational model of the rodent medial prefrontal cortex that accounts for the behavioral sequelae of ACC damage, unifies many of the cognitive functions attributed to it, and provides a solution to an outstanding question in cognitive control research-how the control system determines and motivates what tasks to perform. The theory derives from recent developments in the formal study of hierarchical control and learning that highlight computational efficiencies afforded when collections of actions are represented based on their conjoint goals. According to this position, the ACC utilizes reward information to select tasks that are then accomplished through top-down control over action selection by the striatum. Computational simulations capture animal lesion data that implicate the medial prefrontal cortex in regulating physical and cognitive effort. Overall, this theory provides a unifying theoretical framework for understanding the ACC in terms of the pivotal role it plays in the hierarchical organization of effortful behavior

The Neuroscience of Preferences

The expression of preference reflects the influence of two broad modes of judgment—intuition and deliberation (Kahneman and Frederick 2002). The intuitive mode includes emotional reactions (e.g. Loewenstein 1996), but it also includes heuristic process which are largely perceptual or cognitive in nature. Intuitive processes occur early in a judgment process; they are fast and largely automatic. This is in contrast with deliberative processes which tend to occur later in a judgement process, are slower, and are more controlled. Intuitive and deliberative processes interact with each other, although they are often in conflict, and there is some evidence that they are anatomically separated in the brain

Temporal Prediction Errors in a Passive Learning Task Activate Human Striatum

AbstractFunctional MRI experiments in human subjects strongly suggest that the striatum participates in processing information about the predictability of rewarding stimuli. However, stimuli can be unpredictable in character (what stimulus arrives next), unpredictable in time (when the stimulus arrives), and unpredictable in amount (how much arrives). These variables have not been dissociated in previous imaging work in humans, thus conflating possible interpretations of the kinds of expectation errors driving the measured brain responses. Using a passive conditioning task and fMRI in human subjects, we show that positive and negative prediction errors in reward delivery time correlate with BOLD changes in human striatum, with the strongest activation lateralized to the left putamen. For the negative prediction error, the brain response was elicited by expectations only and not by stimuli presented directly; that is, we measured the brain response to nothing delivered (juice expected but not delivered) contrasted with nothing delivered (nothing expected)

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer

Purpose: The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensitymodulated radiation therapy (IMRT) for oropharynx cancer and to use a model-based approach to investigate the added value of PBT in preventing treatment complications. Methods and Materials: For patients with advanced-stage oropharynx cancer treated with curative intent (PBT, n = 30; IMRT, n = 175), NTCP models were developed using multivariable logistic regression analysis with backward selection. For PBTtreated patients, an equivalent IMRT plan was generated to serve as a reference to determine the benefit of PBT in terms of NTCP. The models were then applied to the PBT-treated patients to compare predicted and observed clinical outcomes (calibration- in-the-large). Five binary endpoints were analyzed at 6 months after treatment: dysphagia >= grade 2, dysphagia >= grade 3, xerostomia >= grade 2, salivary duct inflammation >= grade 2, and feeding tube dependence. Corresponding toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Paired t tests and Wilcoxon rank tests were used to compare mean NTCP results for endpoints between PBT and IMRT. Results: NTCP models developed based on outcomes from all patients were applied to those receiving PBT. NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing significantly higher NTCP values with IMRT. PBT was associated with statistically significant reductions in the mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of >= grade 2 dysphagia and >= grade 2 xerostomia. Conclusions: NTCP models predict significant improvements in the probability of short-term, treatment-related toxicity with PBT compared with IMRT for oropharyngeal cancer. This study demonstrates an NTCP model-based approach to compare predicted patient outcomes when randomized data are not available. (C) 2019 Elsevier Inc. All rights reserved

Age Differences in Striatal Delay Sensitivity during Intertemporal Choice in Healthy Adults

Intertemporal choices are a ubiquitous class of decisions that involve selecting between outcomes available at different times in the future. We investigated the neural systems supporting intertemporal decisions in healthy younger and older adults. Using functional neuroimaging, we find that aging is associated with a shift in the brain areas that respond to delayed rewards. Although we replicate findings that brain regions associated with the mesolimbic dopamine system respond preferentially to immediate rewards, we find a separate region in the ventral striatum with very modest time dependence in older adults. Activation in this striatal region was relatively insensitive to delay in older but not younger adults. Since the dopamine system is believed to support associative learning about future rewards over time, our observed transfer of function may be due to greater experience with delayed rewards as people age. Identifying differences in the neural systems underlying these decisions may contribute to a more comprehensive model of age-related change in intertemporal choice

Desmoglein-2 as a cancer modulator: friend or foe?

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological functions of DSG2 holds promise to exploit this cell surface protein as a potential prognostic biomarker and/or target for better patient outcomes. This review explores the canonical and non-canonical functions of DSG2, as well as the context-dependent impacts of DSG2 in the realm of cancer

The Wick in the Candle of Learning: Epistemic Curiosity Activates Reward Circuitry and Enhances Memory

Curiosity has been described as a desire for learning and knowledge, but its underlying mechanisms are not well understood. We scanned subjects with functional magnetic resonance imaging while they read trivia questions. The level of curiosity when reading questions was correlated with activity in caudate regions previously suggested to be involved in anticipated reward. This finding led to a behavioral study, which showed that subjects spent more scarce resources (either limited tokens or waiting time) to find out answers when they were more curious. The functional imaging also showed that curiosity increased activity in memory areas when subjects guessed incorrectly, which suggests that curiosity may enhance memory for surprising new information. This prediction about memory enhancement was confirmed in a behavioral study: Higher curiosity in an initial session was correlated with better recall of surprising answers 1 to 2 weeks later

Theories of Willpower Affect Sustained Learning

Building cognitive abilities often requires sustained engagement with effortful tasks. We demonstrate that beliefs about willpower–whether willpower is viewed as a limited or non-limited resource–impact sustained learning on a strenuous mental task. As predicted, beliefs about willpower did not affect accuracy or improvement during the initial phases of learning; however, participants who were led to view willpower as non-limited showed greater sustained learning over the full duration of the task. These findings highlight the interactive nature of motivational and cognitive processes: motivational factors can substantially affect people’s ability to recruit their cognitive resources to sustain learning over time