Spontaneous variations in arousal modulate subsequent visual processing and local field potential dynamics in the ferret during quiet wakefulness.

Behavioral states affect neuronal responses throughout the cortex and influence visual processing. Quiet wakefulness (QW) is a behavioral state during which subjects are quiescent but awake and connected to the environment. Here, we examined the effects of pre-stimulus arousal variability on post-stimulus neural activity in the primary visual cortex and posterior parietal cortex in awake ferrets, using pupil diameter as an indicator of arousal. We observed that the power of stimuli-induced alpha (8-12 Hz) decreases when the arousal level increases. The peak of alpha power shifts depending on arousal. High arousal increases inter- and intra-areal coherence. Using a simplified model of laminar circuits, we show that this connectivity pattern is compatible with feedback signals targeting infragranular layers in area posterior parietal cortex and supragranular layers in V1. During high arousal, neurons in V1 displayed higher firing rates at their preferred orientations. Broad-spiking cells in V1 are entrained to high-frequency oscillations (>80 Hz), whereas narrow-spiking neurons are phase-locked to low- (12-18 Hz) and high-frequency (>80 Hz) rhythms. These results indicate that the variability and sensitivity of post-stimulus cortical responses and coherence depend on the pre-stimulus behavioral state and account for the neuronal response variability observed during repeated stimulation.

Different underlying mechanisms for high and low arousal in probabilistic learning in humans.

Humans are uniquely capable of adapting to highly changing environments by updating relevant information and adjusting ongoing behaviour accordingly. Here we show how this ability -termed cognitive flexibility- is differentially modulated by high and low arousal fluctuations. We implemented a probabilistic reversal learning paradigm in healthy participants as they transitioned towards sleep or physical extenuation. The results revealed, in line with our pre-registered hypotheses, that low arousal leads to diminished behavioural performance through increased decision volatility, while performance decline under high arousal was attributed to increased perseverative behaviour. These findings provide evidence for distinct patterns of maladaptive decision-making on each side of the arousal inverted u-shaped curve, differentially affecting participants' ability to generate stable evidence-based strategies, and introduces wake-sleep and physical exercise transitions as complementary experimental models for investigating neural and cognitive dynamics.

Molded polymer-coated composite bone void filler improves tobramycin controlled release kinetics.

Infection remains a significant problem associated with biomedical implants and orthopedic surgeries, especially in revision total joint replacements. Recent advances in antibiotic-releasing bone void fillers (BVF) provide new opportunities to address these types of device-related orthopedic infections that often lead to substantial economic burdens and reduced quality of life. We report improvements made in fabrication and scalability of an antibiotic-releasing polycaprolactone-calcium carbonate/phosphate ceramic composite BVF using a new solvent-free, molten-cast fabrication process. This strategy provides the ability to tailor drug release kinetics from the BVF composite based on modifications of the inorganic substrate and/or the polymeric component, allowing extended tobramycin release at bactericidal concentrations. The mechanical properties of the new BVF composite are comparable to many reported BVFs and validate the relative homogeneity of fabrication. Most importantly, fabrication quality controls are correlated with favorable drug release kinetics, providing bactericidal activity to 10 weeks in vitro when the polycaprolactone component exceeds 98% w/w of the total polymer fraction. Furthermore, in a time kill study, tobramycin-releasing composite fragments inhibited S. aureus growth over 48 h at inoculums as high as 10(9) CFU/mL. This customizable antibiotic-releasing BVF polymer-inorganic biomaterial should provide osseointegrative and osteoconductive properties while contributing antimicrobial protection to orthopedic sites requiring the use of bone void fillers.