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George Zacharopoulos Francesco Sella Roi Cohen Kadosh 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(24)
Formal education has a long-term impact on an individual’s life. However, our knowledge of the effect of a specific lack of education, such as in mathematics, is currently poor but is highly relevant given the extant differences between countries in their educational curricula and the differences in opportunities to access education. Here we examined whether neurotransmitter concentrations in the adolescent brain could classify whether a student is lacking mathematical education. Decreased γ-aminobutyric acid (GABA) concentration within the middle frontal gyrus (MFG) successfully classified whether an adolescent studies math and was negatively associated with frontoparietal connectivity. In a second experiment, we uncovered that our findings were not due to preexisting differences before a mathematical education ceased. Furthermore, we showed that MFG GABA not only classifies whether an adolescent is studying math or not, but it also predicts the changes in mathematical reasoning ∼19 mo later. The present results extend previous work in animals that has emphasized the role of GABA neurotransmission in synaptic and network plasticity and highlight the effect of a specific lack of education on MFG GABA concentration and learning-dependent plasticity. Our findings reveal the reciprocal effect between brain development and education and demonstrate the negative consequences of a specific lack of education during adolescence on brain plasticity and cognitive functions.Educational decisions have a long-lasting impact on both the individual and wider society (1). Mathematical education and attainment has been associated with several quality-of-life indices, including educational progress, socioeconomic status, employment, mental and physical health, and financial stability (2–5). In several countries, such as the United Kingdom and India, 16-y-old adolescents as part of their advanced (i.e., A-level) subjects can choose to stop studying math. The consequences of not choosing math as an A-level subject can be significant. When controlling for potential confounding factors such as socioeconomic status it emerged that the decision to not study math as an A-level subject can lead to an 11% decrease in financial income compared to those who choose to study math as part of their A-level curriculum. No other A-level subject category is associated with such a wage premium (6). In addition, previous studies highlighted the cognitive, emotional, and societal factors that are associated with mathematical education (7, 8).In recent years, there has been significant interest in the investigation of the neural substrates of mathematical cognition and education, and frontal and parietal regions have been repeatedly highlighted as key regions (9–13). Despite the advancement of our knowledge on the neurobiological underpinnings of math abilities, little is known about whether and how they are involved in a lack of mathematical education. At the neurobiological level, the lack of math education could impact neural changes in regions that are involved in skill acquisition of math, primarily in frontoparietal regions (“plasticity account”). This process can be subserved by neurotransmitter concentrations that preceded anatomic changes (14). However, such differences may exist before the continuation of math education and represent baseline differences at the time of the educational decision not to study vs. to study further math (“biomarker account”).Using single H-magnetic resonance spectroscopy (MRS), we scanned two previously defined key regions involved in numeracy: the intraparietal sulcus (IPS) and the middle frontal gyrus (MFG) (Fig. 1). We also examined their functional connectivity using resting-state functional MRI (for reviews see refs. 15–19). Such an approach allowed us to examine the role of γ-aminobutyric acid (GABA) and glutamate, the brain major inhibitory and excitatory neurotransmitters, respectively. Brain inhibition and excitation levels are thought to be critical in triggering the onset and defining the duration of sensitive periods of a given function, during which the neural system is particularly plastic in its response to environmental stimulation (20). It is thought that this is achieved by a shift in the ratio of intrinsic and spontaneous activity and activity in response to the environmental stimulation, whereby the intrinsic and spontaneous activity is reduced and the activity in response to the environmental stimulation is increased (21). Although very early in development, GABA functions as an excitatory neurotransmitter (22), during adolescence GABA and glutamate function as the main inhibitory and excitatory neurotransmitters, respectively, and previous studies have shed some light on the actions of these two neurotransmitters during adolescence. For example, compared to early childhood where there is a peak synaptic density, but the synaptic density is significantly reduced during adolescence (even more so compared to adulthood) and such synaptic pruning is thought to be underpinned by glutamatergic-mediated synaptic mechanisms of long-term potentiation and depression (23). Moreover, previous studies have shown that GABA matures during adolescence, and frontal lobe GABA receptors reach adult levels late in adolescence with lower GABA levels being associated with poor cognitive functioning during adolescence (24, 25).Open in a separate windowFig. 1.Positions of the volumes of interest displayed in a representative T1-weighted image for the (A) IPS and (B) MFG, on axial and sagittal slices, respectively. Average spectra from each of these regions are shown below (thickness corresponds to ±1 SD from the mean) (chemical shift expressed in parts per million, ppm, on the x axis).In the present study, rather than examining a general lack of academic education, which could stem from several confounding factors (e.g., socioeconomic status, lack of learning materials, insufficient educational infrastructure, cultural differences), we specifically examined the lack of math education. As mentioned earlier, in the United Kingdom, 16-y-old adolescents can choose to cease their mathematical education while still being enrolled in other nonmathematical academic education. This allowed us to better control for these confounds by recruiting participants from similar educational systems who differ specifically in their math education.Based on the existing literature reviewed previously, we hypothesized that the lack of mathematical education would be associated with reduced GABA and/or increased glutamate. While both left and right frontoparietal regions were shown to underpin numerical processing (13, 26, 27) in the present study, we focused on the left frontoparietal regions due to their central role in mathematical learning (28–31). Our decision to a priori select the left IPS and MFG was based on the following reasons: First, the left IPS and MFG are frequently reported in neuroimaging studies that examined arithmetic, including a metaanalysis (10). Second, previous studies in the field of numerical cognition have shown the involvement of those brain regions in cognitive training (32–34). Third, brain stimulation studies have suggested a causal role of the MFG in algorithmic learning and the IPS in learning concerning more low-level computation (numerosity, symbolic representation) (30, 35, 36). Using classification approaches, we discerned the differences in these neurotransmitters in adolescents who lack further math education (A-level nonmathematics) vs. those who underwent further math education (A-level mathematics). To dissociate the plasticity account from the biomarker account, we examined in a second experiment an independent cohort of students who made the same decision but who had not yet started their A level. Such a design allowed us to understand the exact role of frontoparietal GABA and glutamate, the main determinants of neuroplasticity and cognitive functions, during this critical developmental and educational stage. 相似文献
947.
Peptide adsorption on a hydrophobic surface results from an interplay of solvation, surface, and intrapeptide forces
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Horinek D Serr A Geisler M Pirzer T Slotta U Lud SQ Garrido JA Scheibel T Hugel T Netz RR 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(8):2842-2847
The hydrophobic effect, i.e., the poor solvation of nonpolar parts of molecules, plays a key role in protein folding and more generally for molecular self-assembly and aggregation in aqueous media. The perturbation of the water structure accounts for many aspects of protein hydrophobicity. However, to what extent the dispersion interaction between molecular entities themselves contributes has remained unclear. This is so because in peptide folding interactions and structural changes occur on all length scales and make disentangling various contributions impossible. We address this issue both experimentally and theoretically by looking at the force necessary to peel a mildly hydrophobic single peptide molecule from a flat hydrophobic diamond surface in the presence of water. This setup avoids problems caused by bubble adsorption, cavitation, and slow equilibration that complicate the much-studied geometry with two macroscopic surfaces. Using atomic-force spectroscopy, we determine the mean desorption force of a single spider-silk peptide chain as F = 58 +/- 8 pN, which corresponds to a desorption free energy of approximately 5 k(B)T per amino acid. Our all-atomistic molecular dynamics simulation including explicit water correspondingly yields the desorption force F = 54 +/- 15 pN. This observation demonstrates that standard nonpolarizable force fields used in classical simulations are capable of resolving the fine details of the hydrophobic attraction of peptides. The analysis of the involved energetics shows that water-structure effects and dispersive interactions give contributions of comparable magnitude that largely cancel out. It follows that the correct modeling of peptide hydrophobicity must take the intimate coupling of solvation and dispersive effects into account. 相似文献
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André Kemmling Fabian Flottmann Nils Daniel Forkert Jens Minnerup Walter Heindel Goetz Thomalla Bernd Eckert Michael Knauth Marios Psychogios Soenke Langner Jens Fiehler 《Journal of cerebral blood flow and metabolism》2015,35(9):1397-1405
Benefit of endovascular recanalization beyond established treatment time windows likely exists in select stroke patients. However, there is currently no imaging model that predicts infarction adjusting for elapsed time between the pathologic snapshot of admission imaging until endovascular recanalization. We trained and cross validated a multivariate generalized linear model (GLM) that uses computer tomography perfusion and clinical data to quantify patient-specific dynamic change of tissue infarction depending on degree and time of recanalization. Multicenter data of 161 patients with proximal anterior circulation occlusion undergoing endovascular therapy were included. Multivariate voxelwise infarct probability was calculated within the GLM. The effect of increasing time to treatment and degree of recanalization on voxelwise infarction was calculated in each patient. Tissue benefit of successful relative to unsuccessful recanalization was shown up to 15 hours after onset in individual patients and decreased nonlinearly with time. On average, the relative reduction of infarct volume at the treatment interval of 5 hours was 53% and this salvage effect decreased by 5% units per hour to <5% after 10 additional hours to treatment. Treatment time-adjusted multivariate prediction of infarction by perfusion and clinical status may identify patients who benefit from extended time to recanalization therapy. 相似文献