Lateral prefrontal cortex and self-control in intertemporal choice.

Disruption of function of left, but not right, lateral prefrontal cortex (LPFC) with low-frequency repetitive transcranial magnetic stimulation (rTMS) increased choices of immediate rewards over larger delayed rewards. rTMS did not change choices involving only delayed rewards or valuation judgments of immediate and delayed rewards, providing causal evidence for a neural lateral-prefrontal cortex-based self-control mechanism in intertemporal choice.

Why Some People Discount More than Others: Baseline Activation in the Dorsal PFC Mediates the Link between COMT Genotype and Impatient Choice

Individuals differ widely in how steeply they discount future rewards. The sources of these stable individual differences in delay discounting (DD) are largely unknown. One candidate is the COMT Val158Met polymorphism, known to modulate prefrontal dopamine levels and affect DD. To identify possible neural mechanisms by which this polymorphism may contribute to stable individual DD differences, we measured 73 participants' neural baseline activation using resting electroencephalogram (EEG). Such neural baseline activation measures are highly heritable and stable over time, thus an ideal endophenotype candidate to explain how genes may influence behavior via individual differences in neural function. After EEG-recording, participants made a series of incentive-compatible intertemporal choices to determine the steepness of their DD. We found that COMT significantly affected DD and that this effect was mediated by baseline activation level in the left dorsal prefrontal cortex (DPFC): (i) COMT had a significant effect on DD such that the number of Val alleles was positively correlated with steeper DD (higher numbers of Val alleles means greater COMT activity and thus lower dopamine levels). (ii) A whole-brain search identified a cluster in left DPFC where baseline activation was correlated with DD; lower activation was associated with steeper DD. (iii) COMT had a significant effect on the baseline activation level in this left DPFC cluster such that a higher number of Val alleles was associated with lower baseline activation. (iv) The effect of COMT on DD was explained by the mediating effect of neural baseline activation in the left DPFC cluster. Our study thus establishes baseline activation level in left DPFC as salient neural signature in the form of an endophenotype that mediates the link between COMT and DD.

Analysis of hand kinematics reveals inter-individual differences in intertemporal decision dynamics

During intertemporal decisions, the preference for smaller, sooner reward over larger-delayed rewards (temporal discounting, TD) exhibits substantial inter-subject variability; however, it is currently unclear what are the mechanisms underlying this apparently idiosyncratic behavior. To answer this question, here we recorded and analyzed mouse movement kinematics during intertemporal choices in a large sample of participants (N = 86). Results revealed a specific pattern of decision dynamics associated with the selection of “immediate” versus “delayed” response alternatives, which well discriminated between a “discounter” versus a “farsighted” behavior—thus representing a reliable behavioral marker of TD preferences. By fitting the Drift Diffusion Model to the data, we showed that differences between discounter and farsighted subjects could be explained in terms of different model parameterizations, corresponding to the use of different choice mechanisms in the two groups. While farsighted subjects were biased toward the “delayed” option, discounter subjects were not correspondingly biased toward the “immediate” option. Rather, as shown by the dynamics of evidence accumulation over time, their behavior was characterized by high choice uncertainty.

The choice of anesthesia influences oxidative energy metabolism and tissue survival in critically ischemic murine skin

In surgical animal studies anesthesia is used regularly. Several reports in the literature demonstrate respiratory and cardiovascular side effects of anesthesiologic agents. The aim of this study was to compare two frequently used anesthesia cocktails (ketamine/xylazine [KX] versus medetomidine/climazolam/fentanyl [MCF]) in skin flap mouse models. Systemic blood values, local metabolic parameters, and surgical outcome should be analyzed in critical ischemic skin flap models. Systemic hypoxia was found in the animals undergoing KX anesthesia compared with normoxia in the MCF group (sO(2): 89.2% +/- 2.4% versus 98.5% +/- 1.2%, P < 0.01). Analysis of tissue metabolism revealed impaired anaerobic oxygen metabolism and increased cellular damage in critical ischemic flap tissue under KX anesthesia (lactate/pyruvate ratio: KX 349.86 +/- 282.38 versus MCF 64.53 +/- 18.63; P < 0.01 and glycerol: KX 333.50 +/- 83.91 micromol/L versus MCF 195.83 +/- 29.49 micromol/L; P < 0.01). After 6 d, different rates of flap tissue necrosis could be detected (MCF 57% +/- 6% versus KX 68% +/- 6%, P < 0.01). In summary we want to point out that the type of anesthesia, the animal model and the goal of the study have to be well correlated. Comparing the effects of KX and MCF anesthesia in mice on surgical outcome was a novel aspect of our study.

Rarely selected distractors in high stakes medical multiple-choice examinations and their recognition by item authors: A simulation and survey

Background Many medical exams use 5 options for multiple choice questions (MCQs), although the literature suggests that 3 options are optimal. Previous studies on this topic have often been based on non-medical examinations, so we sought to analyse rarely selected, 'non-functional' distractors (NF-D) in high stakes medical examinations, and their detection by item authors as well as psychometric changes resulting from a reduction in the number of options. Methods Based on Swiss Federal MCQ examinations from 2005-2007, the frequency of NF-D (selected by <1% or <5% of the candidates) was calculated. Distractors that were chosen the least or second least were identified and candidates who chose them were allocated to the remaining options using two extreme assumptions about their hypothetical behaviour: In case rarely selected distractors were eliminated, candidates could randomly choose another option - or purposively choose the correct answer, from which they had originally been distracted. In a second step, 37 experts were asked to mark the least plausible options. The consequences of a reduction from 4 to 3 or 2 distractors - based on item statistics or on the experts' ratings - with respect to difficulty, discrimination and reliability were modelled. Results About 70% of the 5-option-items had at least 1 NF-D selected by <1% of the candidates (97% for NF-Ds selected by <5%). Only a reduction to 2 distractors and assuming that candidates would switch to the correct answer in the absence of a 'non-functional' distractor led to relevant differences in reliability and difficulty (and to a lesser degree discrimination). The experts' ratings resulted in slightly greater changes compared to the statistical approach. Conclusions Based on item statistics and/or an expert panel's recommendation, the choice of a varying number of 3-4 (or partly 2) plausible distractors could be performed without marked deteriorations in psychometric characteristics.