From Creatures of Habit to Goal-Directed Learners: Tracking the Developmental Emergence of Model-Based Reinforcement Learning.

Theoretical models distinguish two decision-making strategies that have been formalized in reinforcement-learning theory. A model-based strategy leverages a cognitive model of potential actions and their consequences to make goal-directed choices, whereas a model-free strategy evaluates actions based solely on their reward history. Research in adults has begun to elucidate the psychological mechanisms and neural substrates underlying these learning processes and factors that influence their relative recruitment. However, the developmental trajectory of these evaluative strategies has not been well characterized. In this study, children, adolescents, and adults performed a sequential reinforcement-learning task that enabled estimation of model-based and model-free contributions to choice. Whereas a model-free strategy was apparent in choice behavior across all age groups, a model-based strategy was absent in children, became evident in adolescents, and strengthened in adults. These results suggest that recruitment of model-based valuation systems represents a critical cognitive component underlying the gradual maturation of goal-directed behavior.

Experiential reward learning outweighs instruction prior to adulthood.

Throughout our lives, we face the important task of distinguishing rewarding actions from those that are best avoided. Importantly, there are multiple means by which we acquire this information. Through trial and error, we use experiential feedback to evaluate our actions. We also learn which actions are advantageous through explicit instruction from others. Here, we examined whether the influence of these two forms of learning on choice changes across development by placing instruction and experience in competition in a probabilistic-learning task. Whereas inaccurate instruction markedly biased adults' estimations of a stimulus's value, children and adolescents were better able to objectively estimate stimulus values through experience. Instructional control of learning is thought to recruit prefrontal-striatal brain circuitry, which continues to mature into adulthood. Our behavioral data suggest that this protracted neurocognitive maturation may cause the motivated actions of children and adolescents to be less influenced by explicit instruction than are those of adults. This absence of a confirmation bias in children and adolescents represents a paradoxical developmental advantage of youth over adults in the unbiased evaluation of actions through positive and negative experience.

NeuroMix with MR Angiography: A Fast MR Protocol to Reduce Head and Neck CT Angiography for Patients with Acute Neurological Presentations.

BACKGROUND AND PURPOSE: Overuse of computed tomography (CT)-based cerebrovascular imaging in the emergency department (ED) and inpatient settings, notably CT angiography of the head and neck (CTAHN) for minor and non-focal neurological presentations, stresses imaging services and exposes patients to radiation and contrast. Furthermore, such CT-based imaging is often insufficient for definitive diagnosis, necessitating additional MR imaging. Recent advances in fast MRI may allow for timely assessment and reduced need for CTAHN in select populations. MATERIALS AND METHODS: We identified inpatients or ED patients who underwent CTAHN (including non-contrast and post-contrast CTH, with or without CT perfusion [CTP] imaging) followed within 24 hours by a 3T MRI study that included NeuroMix (an unenhanced 2.5 min multi-contrast sequence) and intracranial time-of-flight MR angiography (MRA; a 5 min sequence) during a 9-month period (April to December 2022). Cases were classified by 4 radiologists in consensus as to whether NeuroMix and NeuroMix+MRA detected equivalent findings, detected unique findings, or missed findings relative to CTAHN. RESULTS: 174 cases (mean age 67±16 yrs; 56% female) met the inclusion criteria. NeuroMix alone and NeuroMix+MRA protocols were determined to be equivalent or better compared to CTAHN in 71% and 95% of patients, respectively. NeuroMix always provided equivalent or better assessment of the brain parenchyma, with unique findings on NeuroMix and NeuroMix+MRA in 35% and 36% of cases, respectively, most commonly acute infarction or multiple microhemorrhages. In 8/174 cases (5%), CTAHN identified vascular abnormalities not seen on the NeuroMix+MRA protocol due to CTAHN's wider coverage of the cervical arteries. CONCLUSIONS: A fast MR imaging protocol consisting of NeuroMix+MRA provided equivalent or better information compared to CTAHN in 95% of cases in our population of patients with an acute neurological presentation. The findings provide a deeper understanding of the benefits and challenges of a fast unenhanced MR-first approach with NeuroMix+MRA, which could be used to design prospective trials in select patient groups, with the potential to reduce radiation dose, mitigate adverse contrast-related patient and environmental effects, and lessen the burden on radiologists and healthcare systems. ABBREVIATIONS: CTAHN = CTA Head and Neck including non-contrast and delayed post-contrast CT Head with or without CT perfusion, NeuroMix = unenhanced multi-contrast MR brain sequence.

Consider the source: adolescents and adults similarly follow older adult advice more than peer advice.

Individuals learn which of their actions are likely to be rewarded through trial and error. This form of learning is critical for adapting to new situations, which adolescents frequently encounter. Adolescents are also greatly influenced by their peers. The current study tested the extent to which adolescents rely on peer advice to guide their actions. Adolescent and young adult participants completed a probabilistic learning task in which they chose between four pairs of stimuli with different reinforcement probabilities, with one stimulus in each pair more frequently rewarded. Participants received advice about two of these pairs, once from a similarly aged peer and once from an older adult. Crucially, this advice was inaccurate, enabling the dissociation between experience-based and instruction-based learning. Adolescents and adults learned equally well from experience and no age group difference was evident in the overall influence of advice on choices. Surprisingly, when considering the source of advice, there was no evident influence of peer advice on adolescent choices. However, both adolescents and adults were biased toward choosing the stimulus recommended by the older adult. Contrary to conventional wisdom, these data suggest that adolescents may prioritize the advice of older adults over that of peers in certain decision-making contexts.

Derivation of injury-responsive dendritic cells for acute brain targeting and therapeutic protein delivery in the stroke-injured rat.

Research with experimental stroke models has identified a wide range of therapeutic proteins that can prevent the brain damage caused by this form of acute neurological injury. Despite this, we do not yet have safe and effective ways to deliver therapeutic proteins to the injured brain, and this remains a major obstacle for clinical translation. Current targeted strategies typically involve invasive neurosurgery, whereas systemic approaches produce the undesirable outcome of non-specific protein delivery to the entire brain, rather than solely to the injury site. As a potential way to address this, we developed a protein delivery system modeled after the endogenous immune cell response to brain injury. Using ex-vivo-engineered dendritic cells (DCs), we find that these cells can transiently home to brain injury in a rat model of stroke with both temporal and spatial selectivity. We present a standardized method to derive injury-responsive DCs from bone marrow and show that injury targeting is dependent on culture conditions that maintain an immature DC phenotype. Further, we find evidence that when loaded with therapeutic cargo, cultured DCs can suppress initial neuron death caused by an ischemic injury. These results demonstrate a non-invasive method to target ischemic brain injury and may ultimately provide a way to selectively deliver therapeutic compounds to the injured brain.

Diffraction study of protein crystals grown in cryoloops and micromounts.

Protein crystals are usually grown in hanging or sitting drops and generally get transferred to a loop or micromount for cryocooling and data collection. This paper describes a method for growing crystals on cryoloops for easier manipulation of the crystals for data collection. This study also investigates the steps for the automation of this process and describes the design of a new tray for the method. The diffraction patterns and the structures of three proteins grown by both the new method and the conventional hanging-drop method are compared. The new setup is optimized for the automation of the crystal mounting process. Researchers could prepare nanolitre drops under ordinary laboratory conditions by growing the crystals directly in loops or micromounts. As has been pointed out before, higher levels of supersaturation can be obtained in very small volumes, and the new method may help in the exploration of additional crystallization conditions.