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Chance favors the prepared mind, said Louis Pasteur. Sometimes, significant breakthroughs occur when we creatively integrate new information, leading to a creative insight or an Aha! moment, while at other times when we fail to use a clue, we remain stuck in our habitual thinking patterns. In this study, we hypothesized that the brain's transient oscillatory states would characterize its receptivity or preparedness for such insights. We conducted a real-time brain-state-dependent cognitive stimulation experiment during insightful problem-solving. We showed that participants were more successful in utilizing clues and experienced more Aha responses when these clues were presented at the spontaneously up-regulated state of right temporal alpha oscillation, as opposed to the down-regulated state. Furthermore, we observed an inverse correlation between the coupling of alpha oscillation phase and gamma oscillation power and the frequency of insight. These results shed light on the neural mechanism underpinning the brain's receptivity to integrate upcoming semantic information, emphasizing the pivotal role of dynamical brain oscillations in the Aha! experience. In this study, we focused on finding the brain's receptive state during insightful problem solving – a state where new (semantic) information is successfully integrated to find creative solutions. We predicted that the brain's naturally fluctuating neuronal oscillations, specifically those occurring in the right temporal region, might indicate this receptivity. We recruited healthy volunteers and presented them with word association problems, and provided hints contingent on the brain's spontaneous up (or down) state of the right temporal alpha oscillation (8–12 Hz) on a trial-by-trial basis. We found that participants solved more problems and reported more insights or Aha! moments when hints were presented in the spontaneously up-regulated alpha states. In particular, this effect was specific to alpha and not beta oscillations (16–22 Hz). We also revealed that a phase-amplitude cross-frequency coupling between alpha phase and gamma (50–133 Hz) power was negatively correlated with the frequency of Aha!. This study has established a clear association between right temporal alpha oscillation and the brain's receptivity and Aha! experience through our innovative approach of real-time brain-state-dependent cognitive stimulation. Importantly, our approach is noninvasive, free from adverse side effects, and does not rely on performance feedback, making it convenient, affordable, and readily applicable beyond the laboratory setting. [ABSTRACT FROM AUTHOR]

BackgroundAdenosine deaminase (ADA) deficiency causes severe cellular and humoral immune defects and dysregulation because of metabolic toxicity. Alterations in B-cell development and function have been poorly studied. Enzyme replacement therapy (ERT) and hematopoietic stem cell (HSC) gene therapy (GT) are therapeutic options for patients lacking a suitable bone marrow (BM) transplant donor.ObjectiveWe sought to study alterations in B-cell development in ADA-deficient patients and investigate the ability of ERT and HSC-GT to restore normal B-cell differentiation and function.MethodsFlow cytometry was used to characterize B-cell development in BM and the periphery. The percentage of gene-corrected B cells was measured by using quantitative PCR. B cells were assessed for their capacity to proliferate and release IgM after stimulation.ResultsDespite the severe peripheral B-cell lymphopenia, patients with ADA-deficient severe combined immunodeficiency showed a partial block in central BM development. Treatment with ERT or HSC-GT reverted most BM alterations, but ERT led to immature B-cell expansion. In the periphery transitional B cells accumulated under ERT, and the defect in maturation persisted long-term. HSC-GT led to a progressive improvement in B-cell numbers and development, along with increased levels of gene correction. The strongest selective advantage for ADA-transduced cells occurred at the transition from immature to naive cells. B-cell proliferative responses and differentiation to immunoglobulin secreting IgM after B-cell receptor and Toll-like receptor triggering were severely impaired after ERT and improved significantly after HSC-GT.ConclusionsADA-deficient patients show specific defects in B-cell development and functions that are differently corrected after ERT and HSC-GT.

Using a one-dimensional model, we explore the ability of machine learning to approximate the non-interacting kinetic energy density functional of diatomics. This nonlinear interpolation between Kohn-Sham reference calculations can (i) accurately dissociate a diatomic, (ii) be systematically improved with increased reference data and (iii) generate accurate self-consistent densities via a projection method that avoids directions with no data. With relatively few densities, the error due to the interpolation is smaller than typical errors in standard exchange-correlation functionals.