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People tend to discount the value of future rewards as the delay to receiving them increases. This phenomenon, known as temporal discounting, may underlie many impulsive behaviors, such as drug abuse and overeating. Given the potential role of temporal discounting in maladaptive behaviors, many efforts have been made to find experimental manipulations that reduce temporal discounting. One class of manipulations that has held some promise involves recalling positive autobiographical memories prior to making intertemporal choices. Just as imagining positive future events has been shown to reduce temporal discounting, a few studies have shown that recalling positive past events reduces temporal discounting, especially if memory retrieval evokes positive affective states, such as gratitude and nostalgia. However, we failed to replicate these findings. Here we present an internal meta-analysis combining data from 14 studies ( n = 758) that involved within-subjects positive memory recall-based manipulations. In each study, temporal discounting was assessed using a monetary intertemporal choice task. The average effect size was not significantly different from zero. This finding helps elucidate the neurocognitive mechanisms of temporal discounting; whereas engaging the episodic memory system to imagine future events might promote more patience, engaging the episodic memory system to imagine past events does not.

Study Design: This was a systematic review and meta-analysis., Objective: The objective was (1) to measure rates of successful resolution of dysphagia in patients after undergoing surgical intervention for diffuse idiopathic skeletal hyperostosis (DISH); and (2) to determine if older age, longer duration of preoperative symptoms, or increased severity of disease was correlated with unsuccessful surgical intervention., Summary of Background Data: DISH, also known as Forestier disease, is an enthesopathy affecting up to 35% of the elderly population. Many patients develop osteophytes of the anterior cervical spine, which contribute to chronic symptoms of dysphagia causing debilitating weight loss and possibly resulting in the placement of a permanent gastrostomy feeding tube. For patients that fail conservative medical management, an increase in surgical interventions have been reported in the literature in the last 2 decades., Materials and Methods: A systematic search was performed on PubMed, Medline, Cochrane Library, and Embase. Studies measuring outcomes after surgical intervention for patients with dysphagia from DISH were selected for inclusion. Two independent reviewers screened and assessed all literature in accordance with Cochrane systematic reviewing standards., Results: In total, 22 studies reporting 119 patients were selected for inclusion. Successful relief of dysphagia was obtained in 89% of patients after surgical intervention. Failure to relieve dysphagia was associated with increased length of symptoms preoperatively (P<0.01) using logistic regression. Patients with more severe preoperative symptoms also seem to have an increased risk for treatment failure (risk ratio, 2.86; 95% confidence interval, 1.19-6.85; P=0.02). Treatment failure was not associated with patient age, use of intraoperative tracheostomy, implementation of additional fusion procedures, level of involved segments, or number of involved segments., Conclusions: Patients undergoing surgical intervention have a higher likelihood of failing surgery with increasing preoperative symptom length and increased preoperative symptom severity., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lumen-apposing metal stents (LAMS) may be inserted to create gastrointestinal anastomoses under endoscopic ultrasound (EUS) guidance. This new technique has mostly been evaluated as treatment for gastric outlet obstruction (GOO), especially of malignant origin. Technical success was high in the few and small available studies. Aim of this study was to report our experience with this technique and to identify predictors of success in the setting of a large teaching hospital in Germany., Methods: All subsequent patients who underwent EUS-guided gastrointestinal anastomosis with LAMS from 02/2016 to 08/2019 were included. We performed a retrospective chart analysis including technical procedural details, basic demographic, and health characteristics. Technical success was defined as successful insertion of LAMS. In patients with GOO, the GOO Scoring System was used; an improvement ≥ 1 point was defined as clinical success., Results: Thirty-five patients (22 female, median age: 79 years) were included. Indication for the anastomosis was malignant GOO in 33 patients. In ten patients LAMS was inserted over a guidewire, in 22 patients direct puncture with the electrocautery delivery system of LAMS was performed, and other techniques were used in two patients. Technical success rate was 80.0%. Adverse events occurred in 14.3%. Clinical success rate was 74.3%. Technical success increased and procedure time decreased significantly during the study period. Distance between the two lumina connected with LAMS was significantly shorter (median: 9 mm) in patients with technical success compared to those without (median: 20 mm, P = 0.004). This distance was identified as predictor of success on multivariate analysis., Conclusions: EUS-guided gastrointestinal anastomosis with LAMS is an emerging technique. Its success mainly depends on the distance between the two lumina that are going to be connected by the LAMS and is influenced by the endoscopist's experience.

Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1-3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. PHD expression analysis in 124 colorectal cancer patients revealed that reduced tumoral expression of PHD3 correlated with increased frequency of distant metastases and poor outcome. Tumorigenicity and metastatic potential of colorectal tumor cells over and underexpressing PHD3 were investigated in orthotopic and heterotopic tumor models. PHD3 overexpression in a syngeneic tumor model resulted in fewer liver metastases, whereas PHD3 knockdown induced tumor spread. The migration of PHD3-overexpressing tumor cells was also attenuated in vitro Conversely, migratory potential and colony formation were enhanced in PHD3-deficient cells, and this phenotype was associated with enhanced mitochondrial ATP production. Furthermore, the effects of PHD3 deficiency were accompanied by increased mitochondrial expression of the BCL-2 family member, member myeloid cell leukemia sequence 1 (MCL-1), and could be reversed by simultaneous inhibition of MCL-1. MCL-1 protein expression was likewise enhanced in human colorectal tumors expressing low levels of PHD3. Therefore, we demonstrate that downregulation of PHD3 augments metastatic spread in human colorectal cancer and identify MCL-1 as a novel downstream effector of oxygen sensing. Importantly, these findings offer new insight into the possible, context-specific deleterious effects of pharmacologic PHD inhibition. Cancer Res; 76(8); 2219-30. ©2016 AACR., (©2016 American Association for Cancer Research.)

Planning ability gradually increases throughout childhood. However, it remains unknown whether this is attributable to global factors such as an increased ability and willingness to inhibit premature, impulsive responding, or due to the availability of specific planning operations, such as being able to mentally plan ahead more steps ('search depth') or to derive a clear temporal order of goals by the task layout ('goal hierarchy'). Here, we studied the development of planning ability with respect to these global and problem-specific aspects (search depth and goal hierarchy) of performance in 178 children from 6 to 13 years using the Tower of London task. As expected, global performance gradually developed with age. In accordance, planning durations increasingly reflected global problem demands with longer pre-planning in harder problems. Furthermore, specific planning parameters revealed that children were increasingly capable of mentally searching ahead more steps. In contrast, the ability to derive a goal hierarchy did not show age-related changes. While the global development of planning performance and adaptive planning durations were proposed to primarily reflect enhanced self-monitoring, the specific increase in search depth across childhood that most likely proceeds until young adult age represents more directly planning-related processes. Thus, development of planning ability is supported by multiple contributions., (© 2014 The British Psychological Society.)

Left and right dorsolateral prefrontal cortex (dlPFC) were recently found to be differentially affected by unilateral continuous theta-burst stimulation, reflected in an oppositional alteration of initial thinking time (ITT) in the Tower of London planning task. Here, we further explored this finding using bilateral transcranial direct current stimulation (tDCS) and simultaneous tracking of eye movements. Results revealed a decrease in ITT during concurrent cathodal tDCS of left dlPFC and anodal tDCS of right dlPFC. Eye-movement analyses showed that this facilitating tDCS effect was associated with the actual planning phase, thus reflecting a planning-specific impact of stimulation. For the reverse stimulation pattern of cathodal tDCS of right dlPFC and anodal tDCS of left dlPFC, an increase in gaze shifts was observed, without a significant impact on ITT. Taken together, these findings corroborate that enhanced planning performance can be obtained by boosting right dlPFC and dismantling the inhibitory impact of left dlPFC., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Human control of action in routine situations involves a flexible interplay between (a) task-dependent serial ordering constraints; (b) top-down, or intentional, control processes; and (c) bottom-up, or environmentally triggered, affordances. In addition, the interaction between these influences is modulated by learning mechanisms that, over time, appear to reduce the need for top-down control processes while still allowing those processes to intervene at any point if necessary or if desired. We present a model of the acquisition and control of goal-directed action that goes beyond existing models by operationalizing an interface between two putative systems-a routine and a non-routine system-thereby demonstrating how explicitly represented goals can interact with the emergent task representations that develop through learning in the routine system. The gradual emergence of task representations offers an explanation for the transfer of control with experience from the non-routine goal-based system to the routine system. At the same time it allows action selection to be sensitive both to environmental triggers and to biasing from multiple levels within the goal system., (© 2013 Cognitive Science Society, Inc.)

The development of planning ability in children initially aged four and five was examined longitudinally with a retest-interval of 12 months using the Tower of London task. As expected, problems to solve straightforward without mental look-ahead were mastered by most, even the youngest children. Problems demanding look-ahead were more difficult and accuracy improved significantly with age and over time. This development was strongly moderated by sex: In contrast to coeval boys, four year old girls showed an impressive performance enhancement at age five, reaching the performance of six year olds, whereas four year old boys lagged behind and caught up with girls at the age of six, the typical age of school enrollment. This sex-specific development of planning was clearly separated from overall intelligence: young boys showed a steeper increase in raw intelligence scores than girls, whereas in the older groups scores developed similarly. The observed sex differences in planning development are evident even within a narrow time window of twelve months and may relate to differences in maturational trajectories for girls and boys in dorsolateral prefrontal cortex.

In a companion study, eye-movement analyses in the Tower of London task (TOL) revealed independent indicators of functionally separable cognitive processes during problem solving, with processes of building up an internal representation of the problem preceding actual planning processes. These results imply that processes of internalization and planning should also be distinguishable in time and space with respect to concomitant brain activation patterns. To investigate this possibility, here we conducted analyses of fMRI data for left and right dorsolateral prefrontal cortex (dlPFC) during problem solving in the TOL task by accounting for the trial-by-trial variability of onsets and durations of the different cognitive processing stages. Comparisons between stimulus-locked and response-locked modeling approaches affirmed that activation in left dlPFC was elicited particularly during early processes of internalization, comprising the extraction of goal information and the generation of an internal problem representation, whereas activation in right dlPFC was predominantly attributable to later processes of mental transformations on this representation, that is planning proper. Thus, present data corroborate the proposal that often observed bilateral dlPFC activation patterns during complex cognitive tasks such as problem solving may reflect functionally and, to some extent, even temporally separable processes with opposing lateralizations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Understanding the functional neuroanatomy of planning and problem solving may substantially benefit from better insight into the chronology of the cognitive processes involved. Based on the assumption that regularities in cognitive processing are reflected in overtly observable eye-movement patterns, here we recorded eye movements while participants worked on Tower of London (TOL) problems that comprised an experimental manipulation of different task demands. Single-trial saccade-locked analyses revealed that higher demands on forming an internal problem representation were associated with an increased number of gaze alternations between start state and goal state, but did not show any effect on the durations of these inspections of the states. In contrast, higher demands on actual planning in terms of mental manipulations of working memory contents coincided with a prolonged duration of the very last inspection of the start state (i.e., immediately preceding movement execution) but did not show any effect on the number of gaze alterations. Differential task demands on internalization and planning processes during problem solving hence selectively affect different eye-movement parameters. Moreover, these findings complement previous neuroimaging data on dissociable contributions of left and right dorsolateral prefrontal cortex in problem solving with novel evidence for a corresponding dissociation in the eye-movement patterns reflecting the associated cognitive processes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We present a neural network model of learning and processing the English past tense that is based on the notion that experience-dependent cortical development is a core aspect of cognitive development. During learning the model adds and removes units and connections to develop a task-specific final architecture. The model provides an integrated account of characteristic errors during learning the past tense, adult generalization to pseudoverbs, and dissociations between verbs observed after brain damage in aphasic patients. We put forward a theory of verb inflection in which a functional processing architecture develops through interactions between experience-dependent brain development and the structure of the environment, in this case, the statistical properties of verbs in the language. The outcome of this process is a structured processing system giving rise to graded dissociations between verbs that are easy and verbs that are hard to learn and process. In contrast to dual-mechanism accounts of inflection, we argue that describing dissociations as a dichotomy between regular and irregular verbs is a post hoc abstraction and is not linked to underlying processing mechanisms. We extend current single-mechanism accounts of inflection by highlighting the role of structural adaptation in development and in the formation of the adult processing system. In contrast to some single-mechanism accounts, we argue that the link between irregular inflection and verb semantics is not causal and that existing data can be explained on the basis of phonological representations alone. This work highlights the benefit of taking brain development seriously in theories of cognitive development., (Copyright 2012 APA, all rights reserved.)

We report two experiments in which errors and interaction latencies were recorded during routinization of hierarchically structured computer-based tasks. Experiment 1 demonstrates that action selection is slowed at subtask transitions, especially when selecting lower frequency actions. This frequency effect is compounded by concurrent performance of a secondary, attentionally demanding, task. Experiment 2 replicates these results in a more complex task and further demonstrates that the effects are reduced by experience. Several other factors were also found to affect latencies, including the availability of an external disambiguation cue and the temporal distance over which task context needs to be internally maintained. The results support a "dual-systems" account of action selection in which a "routine" system, sensitive to frequency, context, and experience, is selectively modulated by an attentionally demanding "nonroutine" system.

OXlearn is a free, platform-independent MATLAB toolbox in which standard connectionist neural network models can be set up, run, and analyzed by means of a user-friendly graphical interface. Due to its seamless integration with the MATLAB programming environment, the inner workings of the simulation tool can be easily inspected and/or extended using native MATLAB commands or components. This combination of usability, transparency, and extendability makes OXlearn an efficient tool for the implementation of basic research projects or the prototyping of more complex research endeavors, as well as for teaching. Both the MATLAB toolbox and a compiled version that does not require access to MATLAB can be downloaded from http://psych.brookes.ac.uk/oxlearn/.

Research on Tip of the Tongue (ToT) states has been used to determine whether access to syntactic information precedes access to phonological information. This paper argues that previous studies have used insufficient analyses when investigating the nature of seriality of access. In the first part of this paper, these complex issues are discussed and suitable analyses proposed. In the second part, new experimental data are presented. In Experiment 1, English speakers were asked to give information about mass/count status and initial phoneme of nouns, when in a ToT state. In Experiment 2, German speakers were asked to report grammatical gender and initial phoneme of nouns, when in a ToT state. Evidence that syntactic and phonological information are accessed independently was obtained for both languages. Implications for models of language production and further methodological issues in ToT research are discussed.