Mikail, N. | bioRxiv Science

bioRxiv2026

Single neurons in the human substantia nigra encode social learning signals

Humans are remarkable at adapting to changing norms, yet we know little about how the human brain encodes these social signals at the single neuron level. Here, we recorded the activity of single neurons in the substantia nigra and globus pallidus in neurosurgical participants as they played an iterative ultimatum game versus human and computer avatars. Using computational modeling of behavior, we found that putative dopaminergic units in the substantia nigra tracked the valence of norm prediction errors, with greater encoding during gameplay with human versus computer avatars. Analogous analyses in the globus pallidus, a nucleus adjacent to the substantia nigra, found no significant effect. Our results identify a novel role for the substantia nigra in encoding social learning signals.

neuroscience↗

bioRxiv2021

Rest/Stress Myocardial Perfusion Imaging by Positron Emission Tomography with 18F-Flurpiridaz: A Feasibility Study in Mice

BackgroundMyocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. MethodsRest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 29 mice aged 7-8 months. Regadenoson (0.1 g/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. ResultsTracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7-20.0 mL/cm3/min, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL/cm3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological stress testing for all time intervals assessed. However, while Spearmans coefficients (rs) ranged between 0.478 and 0.672, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20-40 min post tracer injection (R2 [≥]0.98). Notably, K1 and VT were similarly sensitive to pharmacological stress induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate CFR in mice. ConclusionOur findings suggest that a simplified assessment of relative myocardial perfusion and coronary flow reserve (CFR), based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

physiology↗