Tau pathology as determinant of changes in atrophy and cerebral blood flow: a multi-modal longitudinal imaging study.

PURPOSE: Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF. METHODS: We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.1 ± 7.5 years, 44% female, 57% amyloid-ß positive [Aß +], 26 cognitively impaired [CI]) who underwent dynamic [18F]flortaucipir PET and structural MRI at baseline and 25 ± 5 months follow-up. In addition, we included 86 individuals (68 CI) who only underwent baseline dynamic [18F]flortaucipir PET and MRI scans to increase power in our statistical models. We obtained [18F]flortaucipir PET binding potential (BPND) and R1 values reflecting tau load and relative CBF, respectively, and computed cortical thickness from the structural MRI scans using FreeSurfer. We assessed the regional associations between i) baseline and ii) annual change in tau PET BPND in Braak I, III/IV, and V/VI regions and cortical thickness or R1 in cortical gray matter regions (spanning the whole brain) over time using linear mixed models with random intercepts adjusted for age, sex, time between baseline and follow-up assessments, and baseline BPND in case of analyses with annual change as determinant. All analyses were performed in Aß- cognitively normal (CN) individuals and Aß+ (CN and CI) individuals separately. RESULTS: In Aß+ individuals, greater baseline Braak III/IV and V/VI tau PET binding was associated with faster cortical thinning in primarily frontotemporal regions. Annual changes in tau PET were not associated with cortical thinning over time in either Aß+ or Aß- individuals. Baseline tau PET was not associated with longitudinal changes in relative CBF, but increases in Braak III/IV tau PET over time were associated with increases in parietal relative CBF over time in Aß + individuals. CONCLUSION: We showed that higher tau load was related to accelerated cortical thinning, but not to decreases in relative CBF. Moreover, tau PET load at baseline was a stronger predictor of cortical thinning than change of tau PET signal.

In Situ X-ray Absorption Spectroscopy of LaFeO3 and LaFeO3/LaNiO3 Thin Films in the Electrocatalytic Oxygen Evolution Reaction.

We study the electrocatalytic oxygen evolution reaction using in situ X-ray absorption spectroscopy (XAS) to track the dynamics of the valence state and the covalence of the metal ions of LaFeO3 and LaFeO3/LaNiO3 thin films. The active materials are 8 unit cells grown epitaxially on 100 nm conductive La0.67Sr0.33MnO3 layers using pulsed laser deposition (PLD). The perovskite layers are supported on monolayer Ca2Nb3O10 nanosheet-buffered 100 nm SiNx membranes. The in situ Fe and Ni K-edges XAS spectra were measured from the backside of the SiNx membrane using fluorescence yield detection under electrocatalytic reaction conditions. The XAS spectra show significant spectral changes, which indicate that (1) the metal (co)valencies increase, and (2) the number of 3d electrons remains constant with applied potential. We find that the whole 8 unit cells react to the potential changes, including the buried LaNiO3 film.

The substantia nigra in the pathology of schizophrenia: A review on post-mortem and molecular imaging findings.

Dysregulation of striatal dopamine is considered to be an important driver of pathophysiological processes in schizophrenia. Despite being one of the main origins of dopaminergic input to the striatum, the (dys)functioning of the substantia nigra (SN) has been relatively understudied in schizophrenia. Hence, this paper aims to review different molecular aspects of nigral functioning in patients with schizophrenia compared to healthy controls by integrating post-mortem and molecular imaging studies. We found evidence for hyperdopaminergic functioning in the SN of patients with schizophrenia (i.e. increased AADC activity in antipsychotic-free/-naïve patients and elevated neuromelanin accumulation). Reduced GABAergic inhibition (i.e. decreased density of GABAergic synapses, lower VGAT mRNA levels and lower mRNA levels for GABAA receptor subunits), excessive glutamatergic excitation (i.e. increased NR1 and Glur5 mRNA levels and a reduced number of astrocytes), and several other disturbances implicating the SN (i.e. immune functioning and copper concentrations) could potentially underlie this nigral hyperactivity and associated striatal hyperdopaminergic functioning in schizophrenia. These results highlight the importance of the SN in schizophrenia pathology and suggest that some aspects of molecular functioning in the SN could potentially be used as treatment targets or biomarkers.

A High-Entropy Oxide as High-Activity Electrocatalyst for Water Oxidation.

High-entropy materials are an emerging pathway in the development of high-activity (electro)catalysts because of the inherent tunability and coexistence of multiple potential active sites, which may lead to earth-abundant catalyst materials for energy-efficient electrochemical energy storage. In this report, we identify how the multication composition in high-entropy perovskite oxides (HEO) contributes to high catalytic activity for the oxygen evolution reaction (OER), i.e., the key kinetically limiting half-reaction in several electrochemical energy conversion technologies, including green hydrogen generation. We compare the activity of the (001) facet of LaCr0.2Mn0.2Fe0.2Co0.2Ni0.2O3-δ with the parent compounds (single B-site in the ABO3 perovskite). While the single B-site perovskites roughly follow the expected volcano-type activity trends, the HEO clearly outperforms all of its parent compounds with 17 to 680 times higher currents at a fixed overpotential. As all samples were grown as an epitaxial layer, our results indicate an intrinsic composition-function relationship, avoiding the effects of complex geometries or unknown surface composition. In-depth X-ray photoemission studies reveal a synergistic effect of simultaneous oxidation and reduction of different transition metal cations during the adsorption of reaction intermediates. The surprisingly high OER activity demonstrates that HEOs are a highly attractive, earth-abundant material class for high-activity OER electrocatalysts, possibly allowing the activity to be fine-tuned beyond the scaling limits of mono- or bimetallic oxides.

Familiarity mediates the relationship between emotional arousal and pleasure during music listening.

Emotional arousal appears to be a major contributing factor to the pleasure that listeners experience in response to music. Accordingly, a strong positive correlation between self-reported pleasure and electrodermal activity (EDA), an objective indicator of emotional arousal, has been demonstrated when individuals listen to familiar music. However, it is not yet known to what extent familiarity contributes to this relationship. In particular, as listening to familiar music involves expectations and predictions over time based on veridical knowledge of the piece, it could be that such memory factors plays a major role. Here, we tested such a contribution by using musical stimuli entirely unfamiliar to listeners. In a second experiment we repeated the novel music to experimentally establish a sense of familiarity. We aimed to determine whether (1) pleasure and emotional arousal would continue to correlate when listeners have no explicit knowledge of how the tones will unfold, and (2) whether this could be enhanced by experimentally-induced familiarity. In the first experiment, we presented 33 listeners with 70 unfamiliar musical excerpts in two sessions. There was no relationship between the degree of experienced pleasure and emotional arousal as measured by EDA. In the second experiment, 7 participants listened to 35 unfamiliar excerpts over two sessions separated by 30 min. Repeated exposure significantly increased EDA, even though individuals did not explicitly recall having heard all the pieces before. Furthermore, increases in self-reported familiarity significantly enhanced experienced pleasure and there was a general, though not significant, increase in EDA. These results suggest that some level of expectation and predictability mediated by prior exposure to a given piece of music play an important role in the experience of emotional arousal in response to music.

Interactions between the nucleus accumbens and auditory cortices predict music reward value.

We used functional magnetic resonance imaging to investigate neural processes when music gains reward value the first time it is heard. The degree of activity in the mesolimbic striatal regions, especially the nucleus accumbens, during music listening was the best predictor of the amount listeners were willing to spend on previously unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value, which was instead predicted by increasing functional connectivity of these regions with the nucleus accumbens as the reward value increased. Thus, aesthetic rewards arise from the interaction between mesolimbic reward circuitry and cortical networks involved in perceptual analysis and valuation.

Effect of replacing sugar with non-caloric sweeteners in beverages on the reward value after repeated exposure.

BACKGROUND: The reward value of food is partly dependent on learned associations. It is not yet known whether replacing sugar with non-caloric sweeteners in food is affecting long-term acceptance. OBJECTIVE: To determine the effect of replacing sugar with non-caloric sweeteners in a nutrient-empty drink (soft drink) versus nutrient-rich drink (yoghurt drink) on reward value after repeated exposure. DESIGN: We used a randomized crossover design whereby forty subjects (15 men, 25 women) with a mean ± SD age of 21 ± 2 y and BMI of 21.5 ± 1.7 kg/m(2) consumed a fixed portion of a non-caloric sweetened (NS) and sugar sweetened (SS) versions of either a soft drink or a yoghurt drink (counterbalanced) for breakfast which were distinguishable by means of colored labels. Each version of a drink was offered 10 times in semi-random order. Before and after conditioning the reward value of the drinks was assessed using behavioral tasks on wanting, liking, and expected satiety. In a subgroup (n=18) fMRI was performed to assess brain reward responses to the drinks. RESULTS: Outcomes of both the behavioral tasks and fMRI showed that conditioning did not affect the reward value of the NS and SS versions of the drinks significantly. Overall, subjects preferred the yoghurt drinks to the soft drinks and the ss drinks to the NS drinks. In addition, they expected the yoghurt drinks to be more satiating, they reduced hunger more, and delayed the first eating episode more. Conditioning did not influence these effects. CONCLUSION: Our study showed that repeated consumption of a non-caloric sweetened beverage, instead of a sugar sweetened version, appears not to result in changes in the reward value. It cannot be ruled out that learned associations between sensory attributes and food satiating capacity which developed preceding the conditioning period, during lifetime, affected the reward value of the drinks.