Bayesian models of individual differences: combining autistic traits and sensory thresholds to predict motion perception

According to Bayesian models, perception and cognition depend on the optimal combination of noisy incoming evidence with prior knowledge of the world. Individual differences in perception should therefore be jointly determined by a person’s sensitivity to incoming evidence and their prior expectations. Pellicano and Burr (2012) proposed that individuals with autism have flatter priors, suggesting that prior variance is linked to the degree of autistic traits in the general population. We tested this idea by studying how perceived speed changes during pursuit eye-movement and at low contrast. We found that individual differences in these two motion phenomena were predicted by differences in thresholds and autistic traits when combined in a quantitative Bayesian model. Our findings therefore support the flatter-prior hypothesis and suggest that individual differences in prior expectations are more systematic than previously thought. In order to be revealed, however, individual differences in sensitivity must also be taken into account

FXR-Mediated Cortical Cholesterol Accumulation Contributes to the Pathogenesis of Type A Hepatic Encephalopathy

Hepatic encephalopathy is a serious neurologic complication of acute and chronic liver diseases. We previously showed that aberrant bile acid signaling contributes to the development of hepatic encephalopathy via farnesoid X receptor (FXR)-mediated mechanisms in neurons. In the brain, a novel alternative bile acid synthesis pathway, catalyzed by cytochrome p450 46A1 (Cyp46A1), is the primary mechanism by which the brain regulates cholesterol homeostasis. The aim of this study was to determine if FXR activation in the brain altered cholesterol homeostasis during hepatic encephalopathy. Methods: Cyp7A1-/- mice or C57Bl/6 mice pretreated with central infusion of FXR vivo morpholino, 2-hydroxypropyl-β-cyclodextrin, or fed a cholestyramine-supplemented diet were injected with azoxymethane (AOM). Cognitive and neuromuscular impairment as well as liver damage and expression of Cyp46A1 were assessed using standard techniques. The subsequent cholesterol content in the frontal cortex was measured using commercially available kits and by Filipin III and Nile Red staining. Results: There was an increase in membrane-bound and intracellular cholesterol in the cortex of mice treated with AOM that was associated with decreased Cyp46A1 expression. Strategies to inhibit FXR signaling prevented the down-regulation of Cyp46A1 and the accumulation of cholesterol. Treatment of mice with 2-hydroxypropyl-β-cyclodextrin attenuated the AOM-induced cholesterol accumulation in the brain and the cognitive and neuromuscular deficits without altering the underlying liver pathology. Conclusions: During hepatic encephalopathy, FXR signaling increases brain cholesterol and contributes to neurologic decline. Targeting cholesterol accumulation in the brain may be a possible therapeutic target for the management of hepatic encephalopathy

Acute vitamin C improves cardiac function, not exercise capacity, in adults with type 2 diabetes

Abstract Background People with type 2 diabetes (T2D) have impaired exercise capacity, even in the absence of complications, which is predictive of their increased cardiovascular mortality. Cardiovascular dysfunction is one potential cause of this exercise defect. Acute infusion of vitamin C has been separately shown to improve diastolic and endothelial function in prior studies. We hypothesized that acute vitamin C infusion would improve exercise capacity and that these improvements would be associated with improved cardiovascular function. Methods Adults with T2D (n = 31, 7 female, 24 male, body mass index (BMI): 31.5 ± 0.8 kg/m2) and BMI-similar healthy adults (n = 21, 11 female, 10 male, BMI: 30.4 ± 0.7 kg/m2) completed two randomly ordered visits: IV infusion of vitamin C (7.5 g) and a volume-matched saline infusion. During each visit peak oxygen uptake (VO2peak), brachial artery flow mediated dilation (FMD), reactive hyperemia (RH; plethysmography), and cardiac echocardiography were measured. General linear mixed models were utilized to assess the differences in all study variables. Results Acute vitamin C infusion improved diastolic function, assessed by lateral and septal E:E’ (P < 0.01), but did not change RH (P = 0.92), or VO2peak (P = 0.33) in any participants. Conclusion Acute vitamin C infusion improved diastolic function but did not change FMD, forearm reactive hyperemia, or peak exercise capacity. Future studies should further clarify the role of endothelial function as well as other possible physiological causes of exercise impairment in order to provide potential therapeutic targets. Trial registration NCT00786019. Prospectively registered May 200

Bayesian Models of Individual Differences

According to Bayesian models, perception and cognition depend on the optimal combination of noisy incoming evidence with prior knowledge of the world. Individual differences in perception should therefore be jointly determined by a person’s sensitivity to incoming evidence and their prior expectations. Pellicano and Burr (2012) proposed that individuals with autism have flatter priors, suggesting that prior variance is linked to the degree of autistic traits in the general population. We tested this idea by studying how perceived speed changes during pursuit eye-movement and at low contrast. We found that individual differences in these two motion phenomena were predicted by differences in thresholds and autistic traits when combined in a quantitative Bayesian model. Our findings therefore support the flatter-prior hypothesis and suggest that individual differences in prior expectations are more systematic than previously thought. In order to be revealed, however, individual differences in sensitivity must also be taken into account