The In Vivo Biological Fate of Protein Corona: A Comparative PET Study of the Fate of Soft and Hard Protein Corona in Healthy Animal Models.

Radiolabeling and nuclear imaging techniques are used to investigate the biodistribution patterns of the soft and hard protein corona around poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) after administration to healthy mice. Soft and hard protein coronas of 131I-labeled BSA or 131I-labeled serum are formed on PLGA NPs functionalized with either polyehtylenimine (PEI) or bovine serum albumin (BSA). The exchangeability of hard and soft corona is assessed in vitro by gamma counting exposing PLGA NPs with corona to non-labeled BSA, serum, or simulated body fluid. PEI PLGA NPs form larger and more stable coronas than BSA PLGA NPs. Soft coronas are more exchangeable than hard ones. The in vivo fate of PEI PLGA NPs coated with preformed 18F-labeled BSA hard and soft coronas is assessed by positron emission tomography (PET) following intravenous administration. While the soft corona shows a biodistribution similar to free 18F BSA with high activity in blood and kidney, the hard corona follows patterns characteristic of nanoparticles, accumulating in the lungs, liver, and spleen. These results show that in vivo fates of soft and hard corona are different, and that soft corona is more easily exchanged with proteins from the body, while hard corona is largely retained on the nanoparticle surface.

Successful metabolic control in diabetes type 1 depends on individual neuroeconomic and health risk-taking decision endophenotypes: a new target in personalized care.

BACKGROUND: Neurobehavioral decision profiles have often been neglected in chronic diseases despite their direct impact on major public health issues such as treatment adherence. This remains a major concern in diabetes, despite intensive efforts and public awareness initiatives regarding its complications. We hypothesized that high rates of low adherence are related to risk-taking profiles associated with decision-making phenotypes. If this hypothesis is correct, it should be possible to define these endophenotypes independently based both on dynamic measures of metabolic control (HbA1C) and multidimensional behavioral profiles. METHODS: In this study, 91 participants with early-stage type 1 diabetes fulfilled a battery of self-reported real-world risk behaviors and they performed an experimental task, the Balloon Analogue Risk Task (BART). RESULTS: K-means and two-step cluster analysis suggest a two-cluster solution providing information of distinct decision profiles (concerning multiple domains of risk-taking behavior) which almost perfectly match the biological partition, based on the division between stable or improving metabolic control (MC, N = 49) v. unstably high or deteriorating states (NoMC, N = 42). This surprising dichotomy of behavioral phenotypes predicted by the dynamics of HbA1C was further corroborated by standard statistical testing. Finally, the BART game enabled to identify groups differences in feedback learning and consequent behavioral choices under ambiguity, showing distinct group choice behavioral patterns. CONCLUSIONS: These findings suggest that distinct biobehavioral endophenotypes can be related to the success of metabolic control. These findings also have strong implications for programs to improve patient adherence, directly addressing risk-taking profiles.

Evidence for a differential interference of noise in sub-lexical and lexical reading routes in healthy participants and dyslexics.

The ineffective exclusion of surrounding noise has been proposed to underlie the reading deficits in developmental dyslexia. However, previous studies supporting this hypothesis focused on low-level visual tasks, providing only an indirect link of noise interference on reading processes. In this study, we investigated the effect of noise on regular, irregular, and pseudoword reading in 23 dyslexic children and 26 age- and IQ-matched controls, by applying the white noise displays typically used to validate this theory to a lexical decision task. Reading performance and eye movements were measured. Results showed that white noise did not consistently affect dyslexic readers more than typical readers. Noise affected more dyslexic than typical readers in terms of reading accuracy, but it affected more typical than dyslexic readers in terms of response time and eye movements (number of fixations and regressions). Furthermore, in typical readers, noise affected more the speed of reading of pseudowords than real words. These results suggest a particular impact of noise on the sub-lexical reading route where attention has to be deployed to individual letters. The use of a lexical route would reduce the effect of noise. A differential impact of noise between words and pseudowords may therefore not be evident in dyslexic children if they are not yet proficient in using the lexical route. These findings indicate that the type of reading stimuli and consequent reading strategies play an important role in determining the effects of noise interference in reading processing and should be taken into account by further studies.

Trust-based health decision-making recruits the neural interoceptive saliency network which relates to temporal trajectories of Hemoglobin A1C in Diabetes Type 1.

Experimental approaches in neuroeconomics generally involve monetary utility. Utility in the health domain is relevant in diabetes because constant daily life decisions are critical for self-consequential long-term outcomes. We used fMRI to investigate self-consequent decision-making in the health and economic domains in Type 1 Diabetes Mellitus and controls (N = 50). We focused on two critical phases of decision-making: Investment and Feedback (Positive or Negative). Patients showed larger BOLD activation of limbic, and reward/dopaminergic regions in particular in the health trust game. Importantly, the worse the trajectory of metabolic control (increasing HbA1C), the higher the BOLD activity in regions of the interoceptive saliency network. This was manifested by positive correlations between brain activity during investment in anterior cingulate cortex and insula and HbA1c blood level progression. We conclude that the neural correlates of health-consequent decision-making domain involve limbic and reward related dopaminergic regions in Type 1 Diabetes Mellitus. Furthermore, the temporal trajectory of HbA1C blood levels is correlated with neural risk processing in the saliency network. Evidence for differential risk processing in the health versus the neuroeconomic context, and the discovery of a role for the saliency interoceptive network in metabolic control trajectories suggests a new perspective on the development of personalized interventions.

Trust-Based Decision-Making in the Health Context Discriminates Biological Risk Profiles in Type 1 Diabetes.

Theoretical accounts on social decision-making under uncertainty postulate that individual risk preferences are context dependent. Generalization of models of decision-making to dyadic interactions in the personal health context remain to be experimentally addressed. In economic utility-based models, interactive behavioral games provide a framework to investigate probabilistic learning of sequential reinforcement. Here, we model an economic trust game in the context of a chronic disease (Diabetes Type 1) which involves iterated daily decisions in complex social contexts. Ninety-one patients performed experimental trust games in both economic and health settings and were characterized by a multiple self-report set of questionnaires. We found that although our groups can correctly infer pay-off contingencies, they behave differently because patients with a biological profile of preserved glycemic control show adaptive choice behavior both in economic and health domains. On the other hand, patients with a biological profile of loss of glycemic control presented a contrasting behavior, showing non-adaptive choices on both contexts. These results provide a direct translation from neuroeconomics to decision-making in the health domain and biological risk profiles, in a behavioral setting that requires difficult and self-consequential decisions with health impact. Our findings also provide a contextual generalization of mechanisms underlying individual decision-making under uncertainty.

Abnormal Responses in Cognitive Impulsivity Circuits Are Associated with Glycosylated Hemoglobin Trajectories in Type 1 Diabetes Mellitus and Impaired Metabolic Control.

BACKGROUND: Risky health decisions and impulse control profiles may impact on metabolic control in type 1 diabetes mellitus (T1DM). We hypothesize that the neural correlates of cognitive impulsivity and decision-making in T1DM relate to metabolic control trajectories. METHODS: We combined functional magnetic resonance imaging (fMRI), measures of metabolic trajectories (glycosylated hemoglobin [HbA1c] over multiple time points) and behavioral assessment using a cognitive impulsivity paradigm, the Balloon Analogue Risk Task (BART), in 50 participants (25 T1DM and 25 controls). RESULTS: Behavioral results showed that T1DM participants followed a rigid conservative risk strategy along the iterative game. Imaging group comparisons showed that patients showed larger activation of reward related, limbic regions (nucleus accumbens, amygdala) and insula (interoceptive saliency network) in initial game stages. Upon game completion differences emerged in relation to error monitoring (anterior cingulate cortex [ACC]) and inhibitory control (inferior frontal gyrus). Importantly, activity in the saliency network (ACC and insula), which monitors interoceptive states, was related with metabolic trajectories, which was also found for limbic/reward networks. Parietal and posterior cingulate regions activated both in controls and patients with adaptive decision-making, and positively associated with metabolic trajectories. CONCLUSION: We found triple converging evidence when comparing metabolic trajectories, patients versus controls or risk averse (non-learners) versus patients who learned by trial and error. Dopaminergic reward and saliency (interoceptive and error monitoring) circuits show a tight link with impaired metabolic trajectories and cognitive impulsivity in T1DM. Activity in parietal and posterior cingulate are associated with adaptive trajectories. This link between reward-saliency-inhibition circuits suggests novel strategies for patient management.

Visual Perception and Reading: New Clues to Patterns of Dysfunction Across Multiple Visual Channels in Developmental Dyslexia.

Purpose: The specificity of visual channel impairment in dyslexia has been the subject of much controversy. The purpose of this study was to determine if a differential pattern of impairment can be verified between visual channels in children with developmental dyslexia, and in particular, if the pattern of deficits is more conspicuous in tasks where the magnocellular-dorsal system recruitment prevails. Additionally, we also aimed at investigating the association between visual perception thresholds and reading. Methods: In the present case-control study, we compared perception thresholds of 33 children diagnosed with developmental dyslexia and 34 controls in a speed discrimination task, an achromatic contrast sensitivity task, and a chromatic contrast sensitivity task. Moreover, we addressed the correlation between the different perception thresholds and reading performance, as assessed by means of a standardized reading test (accuracy and fluency). Group comparisons were performed by the Mann-Whitney U test, and Spearman's rho was used as a measure of correlation. Results: Results showed that, when compared to controls, children with dyslexia were more impaired in the speed discrimination task, followed by the achromatic contrast sensitivity task, with no impairment in the chromatic contrast sensitivity task. These results are also consistent with the magnocellular theory since the impairment profile of children with dyslexia in the visual threshold tasks reflected the amount of magnocellular-dorsal stream involvement. Moreover, both speed and achromatic thresholds were significantly correlated with reading performance, in terms of accuracy and fluency. Notably, chromatic contrast sensitivity thresholds did not correlate with any of the reading measures. Conclusions: Our evidence stands in favor of a differential visual channel deficit in children with developmental dyslexia and contributes to the debate on the pathophysiology of reading impairments.

Tribal love: the neural correlates of passionate engagement in football fans.

The tribal character of the affective link between football fans and their teams is a well-recognized phenomenon. Other forms of love such as romantic or maternal attachment have previously been studied from a neuroimaging point of view. Here we aimed to investigate the neural basis of this tribal form of love, which implies both the feeling of belongingness and rivalry against opposing teams. A pool of 56 participants was submitted to an fMRI experimental design involving the presentation of winning and losing football moments of their loved, rival or neutral teams. We found recruitment of amygdala and reward regions, including the ventral tegmental area (VTA) and substantia nigra (SN), as well as other limbic regions involved in emotional cognition, for 'positive vs neutral' and 'positive vs negative' conditions. The latter contrast was correlated with neuropsychological scores of fanaticism in the amygdala and regions within the reward system, as the VTA and SN. The observation of increased response patterns in critical components of the reward system, in particular for positive content related to the loved team, suggests that this kind of non-romantic love reflects a specific arousal and motivational state, which is biased for emotional learning of positive outcomes.