Nicholas D. Wright

Disruption of Dorsolateral Prefrontal Cortex Decreases Model-Based in Favor of Model-free Control in Humans

Summary Human choice behavior often reflects a competition between inflexible computationally efficient control on the one hand and a slower more flexible system of control on the other. This distinction is well captured by model-free and model-based reinforcement learning algorithms. Here, studying human subjects, we show it is possible to shift the balance of control between these systems by disruption of right dorsolateral prefrontal cortex, such that participants manifest a dominance of the less optimal model-free control. In contrast, disruption of left dorsolateral prefrontal cortex impaired model-based performance only in those participants with low working memory capacity.

Deconstructing risk: Separable encoding of variance and skewness in the brain

Risky choice entails a need to appraise all possible outcomes and integrate this information with individual risk preference. Risk is frequently quantified solely by statistical variance of outcomes, but here we provide evidence that individuals’ choice behaviour is sensitive to both dispersion (variance) and asymmetry (skewness) of outcomes. Using a novel behavioural paradigm in humans, we independently manipulated these ‘summary statistics’ while scanning subjects with fMRI. We show that a behavioural sensitivity to variance and skewness is mirrored in neuroanatomically dissociable representations of these quantities, with parietal cortex showing sensitivity to the former and prefrontal cortex and ventral striatum to the latter. Furthermore, integration of these objective risk metrics with subjective risk preference is expressed in a subject-specific coupling between neural activity and choice behaviour in anterior insula. Our findings show that risk is neither monolithic from a behavioural nor neural perspective and its decomposition is evident both in distinct behavioural preferences and in segregated underlying brain representations.

Selective Activation Around the Left Occipito-Temporal Sulcus for Words Relative to Pictures: Individual Variability or False Positives?

We used high‐resolution fMRI to investigate claims that learning to read results in greater left occipito‐temporal (OT) activation for written words relative to pictures of objects. In the first experiment, 9/16 subjects performing a one‐back task showed activation in ≥1 left OT voxel for words relative to pictures (P < 0.05 uncorrected). In a second experiment, another 9/15 subjects performing a semantic decision task activated ≥1 left OT voxel for words relative to pictures. However, at this low statistical threshold false positives need to be excluded. The semantic decision paradigm was therefore repeated, within subject, in two different scanners (1.5 and 3 T). Both scanners consistently localised left OT activation for words relative to fixation and pictures relative to words, but there were no consistent effects for words relative to pictures. Finally, in a third experiment, we minimised the voxel size (1.5 × 1.5 × 1.5 mm3) and demonstrated a striking concordance between the voxels activated for words and pictures, irrespective of task (naming vs. one‐back) or script (English vs. Hebrew). In summary, although we detected differential activation for words relative to pictures, these effects: (i) do not withstand statistical rigour; (ii) do not replicate within or between subjects; and (iii) are observed in voxels that also respond to pictures of objects. Our findings have implications for the role of left OT activation during reading. More generally, they show that studies using low statistical thresholds in single subject analyses should correct the statistical threshold for the number of comparisons made or replicate effects within subject. Hum Brain Mapp 2008.

Approach-avoidance processes contribute to dissociable impacts of risk and loss on choice

Value-based choices are influenced both by risk in potential outcomes and by whether outcomes reflect potential gains or losses. These variables are held to be related in a specific fashion, manifest in risk aversion for gains and risk seeking for losses. Instead, we hypothesized that there are independent impacts of risk and loss on choice such that, depending on context, subjects can show either risk aversion for gains and risk seeking for losses or the exact opposite. We demonstrate this independence in a gambling task, by selectively reversing a loss-induced effect (causing more gambling for gains than losses and the reverse) while leaving risk aversion unaffected. Consistent with these dissociable behavioral impacts of risk and loss, fMRI data revealed dissociable neural correlates of these variables, with parietal cortex tracking risk and orbitofrontal cortex and striatum tracking loss. Based on our neural data, we hypothesized that risk and loss influence action selection through approach–avoidance mechanisms, a hypothesis supported in an experiment in which we show valence and risk-dependent reaction time effects in line with this putative mechanism. We suggest that in the choice process risk and loss can independently engage approach–avoidance mechanisms. This can provide a novel explanation for how risk influences action selection and explains both classically described choice behavior as well as behavioral patterns not predicted by existing theory.

Assaying the Effect of Levodopa on the Evaluation of Risk in Healthy Humans

In humans, dopamine is implicated in reward and risk-based decision-making. However, the specific effects of dopamine augmentation on risk evaluation are unclear. Here we sought to measure the effect of 100 mg oral levodopa, which enhances synaptic release of dopamine, on choice behaviour in healthy humans. We use a paradigm without feedback or learning, which solely isolates effects on risk evaluation. We present two studies (n = 20; n = 20) employing a randomised, placebo-controlled, within-subjects design. We manipulated different dimensions of risk in a controlled economic paradigm. We test effects on risk-reward tradeoffs, assaying both aversion to variance (the spread of possible outcomes) and preference for relative losses and gains (asymmetry of outcomes - skewness), dissociating this from potential non-specific effects on choice randomness using behavioural modelling. There were no systematic effects of levodopa on risk attitudes, either for variance or skewness. However, there was a drift towards more risk-averse behaviour over time, indicating that this paradigm was sensitive to detect changes in risk-preferences. These findings suggest that levodopa administration does not change the evaluation of risk. One possible reason is that dopaminergic influences on decision making may be due to changing the response to reward feedback.

Human responses to unfairness with primary rewards and their biological limits

Humans bargaining over money tend to reject unfair offers, whilst chimpanzees bargaining over primary rewards of food do not show this same motivation to reject. Whether such reciprocal fairness represents a predominantly human motivation has generated considerable recent interest. We induced either moderate or severe thirst in humans using intravenous saline, and examined responses to unfairness in an Ultimatum Game with water. We ask if humans also reject unfair offers for primary rewards. Despite the induction of even severe thirst, our subjects rejected unfair offers. Further, our data provide tentative evidence that this fairness motivation was traded-off against the value of the primary reward to the individual, a trade-off determined by the subjective value of water rather than by an objective physiological metric of value. Our data demonstrate humans care about fairness during bargaining with primary rewards, but that subjective self-interest may limit this fairness motivation.

Testosterone induces off-line perceptual learning.

RationalePerceptual learning operates on distinct timescales. How different neuromodulatory systems impact on learning across these different timescales is poorly understood.ObjectivesHere, we test the causal impact of a novel influence on perceptual learning, the androgen hormone testosterone, across distinct timescales.MethodsIn a double-blind, placebo- controlled, cross-over study with testosterone, subjects undertook a simple contrast detection task during training sessions on two separate days.ResultsOn placebo, there was no learning either within training sessions or between days, except for a fast, rapidly saturating, improvement early on each testing day. However, testosterone caused “off-line” learning, with no learning seen within training sessions, but a marked performance improvement over the days between sessions. This testosterone-induced learning occurred in the absence of changes in subjective confidence or introspective accuracy.ConclusionsOur findings show that testosterone influences perceptual learning on a timescale consistent with an influence on “off-line” consolidation processes.

Developmental changes in effects of risk and valence on adolescent decision-making

Highlights • Risk and valence influence choices in decision-making tasks.• Adolescents aged 11–16 took part in a gambling task.• Influences of risk and valence on decisions showed different development patterns.• Risk-aversion remained stable while the influence of valence reduced with age.

Distinct encoding of risk and value in economic choice between multiple risky options

Neural encoding of value-based stimuli is suggested to involve representations of summary statistics, including risk and expected value (EV). A more complex, but ecologically more common, context is when multiple risky options are evaluated together. However, it is unknown whether encoding related to option evaluation in these situations involves similar principles. Here we employed fMRI during a task that parametrically manipulated EV and risk in two simultaneously presented lotteries, both of which contained either gains or losses. We found representations of EV in medial prefrontal cortex and anterior insula, an encoding that was dependent on which option was chosen (i.e. chosen and unchosen EV) and whether the choice was over gains or losses. Parietal activity reflected whether the riskier or surer option was selected, whilst activity in a network of regions that also included parietal cortex reflected both combined risk and difference in risk for the two options. Our findings provide support for the idea that summary statistics underpin a representation of value-based stimuli, and further that these summary statistics undergo distinct forms of encoding.

The chronometry of risk processing in the human cortex

The neuroscience of human decision-making has focused on localizing brain activity correlating with decision variables and choice, most commonly using functional MRI (fMRI). Poor temporal resolution means these studies are agnostic in relation to how decisions unfold in time. Consequently, here we address the temporal evolution of neural activity related to encoding of risk using magnetoencephalography (MEG), and show modulations of electromagnetic power in posterior parietal and dorsomedial prefrontal cortex (DMPFC) which scale with both variance and skewness in a lottery, detectable within 500 ms following stimulus presentation. Electromagnetic responses in somatosensory cortex following this risk encoding predict subsequent choices. Furthermore, within anterior insula we observed early and late effects of subject-specific risk preferences, suggestive of a role in both risk assessment and risk anticipation during choice. The observation that cortical activity tracks specific and independent components of risk from early time-points in a decision-making task supports the hypothesis that specialized brain circuitry underpins risk perception.