Faculty Bibliography

OBJECTIVE: To assess the decision-making impairment in patients with multiple sclerosis (MS) and how they relate to other cognitive domains. METHODS: We performed a cross-sectional analysis in 84 patients with MS, and 21 matched healthy controls using four tasks taken from behavioral economics: (1) risk preferences, (2) choice consistency, (3) delay of gratification, and (4) rate of learning. All tasks were conducted using real-world reward outcomes (food or money) in different real-life conditions. Participants underwent cognitive examination using the Brief Repeatable Battery-Neuropsychology. RESULTS: Patients showed higher risk aversion (general propensity to choose the lottery was 0.51 vs 0.64, p = 0.009), a trend to choose more immediate rewards over larger but delayed rewards ( p = 0.108), and had longer reactions times ( p = 0.033). Choice consistency and learning rates were not different between groups. Progressive patients chose slower than relapsing patients. In relation to general cognitive impairments, we found correlations between impaired decision-making and impaired verbal memory ( r = 0.29, p = 0.009), visual memory ( r = -0.37, p = 0.001), and reduced processing speed ( r = -0.32, p = 0.001). Normalized gray matter volume correlated with deliberation time ( r = -0.32, p = 0.005). CONCLUSION: Patients with MS suffer significant decision-making impairments, even at the early stages of the disease, and may affect patients' quality and social life.

Weather, in particular the intensity and duration of sunshine (luminance), has been shown to significantly affect financial markets. Yet, because of the complexity of market interactions we do not know how human behavior is affected by luminance in a way that could inform theoretical choice models. In this paper, we use data from a field study using an incentive-compatible, decision task conducted daily over a period of two years and from the US Earth System Research Laboratory luminance sensor to investigate the impact of luminance on risk preferences, ambiguity preferences, choice consistency and dominance violations. We find that luminance levels affect all of these. Age and gender influence the strength of some of these effects.

In intertemporal choices between immediate and delayed rewards, people tend to prefer immediate rewards, often even when the delayed reward is larger. This is known as temporal discounting. It has been proposed that this tendency emerges because immediate rewards are more emotionally arousing than delayed rewards. However, in our previous research, we found no evidence for this but instead found that arousal responses (indexed with pupil dilation) in intertemporal choice are context-dependent. Specifically, arousal tracks the subjective value of the more variable reward option in the paradigm, whether it is immediate or delayed. Nevertheless, people tend to choose the less variable option in the choice task. In other words, their choices are reference-dependent and depend on variance in their recent history of offers. This suggests that there may be a causal relationship between reference-dependent choice and arousal, which we investigate here by reducing arousal pharmacologically using propranolol. Here, we show that propranolol reduces reference-dependence, leading to choices that are less influenced by recent history and more internally consistent.

The population of people above 65 years old continues to grow and there is mounting evidence that as humans age, they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole brain voxel based morphometry (VBM) analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference (GARP). All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared to younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong co-activation patterns with nearly all of the value-associated regions identified in previous studies.These findings point towards a neuroanatomic locus for economic rationality in the aging brain, and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making. Significance Statement Age is a crucial factor in decision making, with older individuals making more errors in choices. Using whole brain voxel based morphometry (VBM) analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference (GARP). Furthermore, this brain area strongly co-activates with other reward-associated regions identified with Neurosynth. These findings point towards a role for neuroscientific discoveries in shaping long-standing economic views of decision-making.

During development a limited number of progenitors generate diverse cell types that comprise the nervous system. Neuronal diversity, which arises largely at the level of neural stem cells, is critical for brain function. Often these cells exhibit temporal patterning: they sequentially produce neurons of distinct cell fates as a consequence of intrinsic and/or extrinsic cues. Here, we review recent advances in temporal patterning during neuronal specification, focusing on conserved players and mechanisms in invertebrate and vertebrate models. These studies underscore temporal patterning as an evolutionarily conserved strategy to generate neuronal diversity. Understanding the general principles governing temporal patterning and the molecular players involved will improve our ability to direct neural progenitors towards specific neuronal fates for brain repair.

The Drosophila visual system has become a premier model for probing how neural diversity is generated during development. Recent work has provided deeper insight into the elaborate mechanisms that control the range of types and numbers of neurons produced, which neurons survive, and how they interact. These processes drive visual function and behavioral preferences. Other studies are beginning to provide insight into how neuronal diversity evolved in insects by adding new cell types and modifying neural circuits. Some of the most powerful comparisons have been those made to the Drosophila visual system, where a deeper understanding of molecular mechanisms allows for the generation of hypotheses about the evolution of neural anatomy and function. The evolution of new neural types contributes additional complexity to the brain and poses intriguing questions about how new neurons interact with existing circuitry. We explore how such individual changes in a variety of species might play a role over evolutionary timescales. Lessons learned from the fly visual system apply to other neural systems, including the fly central brain, where decisions are made and memories are stored. Expected final online publication date for the Annual Review of Genetics Volume 51 is November 23, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Stem cells self-renew and produce progenitors with limited proliferative potential. Reporting in Developmental Cell, Liu et al. (2017) demonstrate that in some neural stem cells, Notch activity is asymmetrically amplified by a positive feedback loop with the super elongation complex (SEC) to quickly differentiate between stem cells and progenitors.

Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the Drosophila visual system to investigate how development is coordinated to establish retinotopy, a feature of all visual systems. Photoreceptors achieve retinotopy by inducing their target field in the optic lobe, the lamina neurons, with a secreted differentiation cue, epidermal growth factor (EGF). We find that communication between photoreceptors and lamina cells requires a signaling relay through glia. In response to photoreceptor-EGF, glia produce insulin-like peptides, which induce lamina neuronal differentiation. Our study identifies a role for glia in coordinating neuronal development across distinct brain regions, thus reconciling the timing of column assembly with that of delayed differentiation, as well as the spatiotemporal pattern of lamina neuron differentiation.

In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neuron, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar neurons contact multiple columns. Here we show that combinatorial inputs from temporal and spatial axes generate this neuronal diversity: all neuroblasts switch fates over time to produce different neurons; the neuroepithelium that generates neuroblasts is also subdivided into six compartments by the expression of specific factors. Uni-columnar neurons are produced in all spatial compartments independently of spatial input; they innervate the neuropil where they are generated. Multi-columnar neurons are generated in smaller numbers in restricted compartments and require spatial input; the majority of their cell bodies subsequently move to cover the entire medulla. The selective integration of spatial inputs by a fixed temporal neuroblast cascade thus acts as a powerful mechanism for generating neural diversity, regulating stoichiometry and the formation of retinotopy.