Riemann-Based Algorithms Assessment for Single- and Multiple-Trial P300 Classification in Non-Optimal Environments.

The P300 wave is commonly used in Brain-Computer Interface technology due to its higher bit rates when compared to other BCI paradigms. P300 classification pipelines based on Riemannian Geometry provide accuracies on par with state-of-the-art pipelines, without having the need for spatial filters, and also possess the ability to be calibrated with little data. In this study, five different P300 detection pipelines are compared, with three of them using Riemannian Geometry as either feature extraction or classification algorithms. The goal of this study is to assess the viability of Riemannian Geometry-based methods in non-optimal environments with sudden background noise changes, rather than maximizing classification accuracy values. For fifteen subjects, the average single-trial accuracy obtained for each pipeline was: 56.06% for Linear Discriminant Analysis (LDA), 72.13% for Bayesian Linear Discriminant Analysis (BLDA), 63.56% for Riemannian Minimum Distance to Mean (MDM), 69.22% for Riemannian Tangent Space with Logistic Regression (TS-LogR), and 63.30% for Riemannian Tangent Space with Support Vector Machine (TS-SVM). The results are higher for the pipelines based on BLDA and TS-LogR, suggesting that they could be viable methods for the detection of the P300 component when maximizing the bit rate is needed. For multiple-trial classification, the BLDA pipeline converged faster towards higher average values, closely followed by the TS-LogR pipeline. The two remaining Riemannian methods' accuracy also increases with the number of trials, but towards a lower value compared to the aforementioned ones. Single-stimulus detection metrics revealed that the TS-LogR pipeline can be a viable classification method, as its results are only slightly lower than those obtained with BLDA. P300 waveforms were also analyzed to check for evidence of the component being elicited. Finally, a questionnaire was used to retrieve the most intuitive focusing methods employed by the subjects.

Time course of arsenic species in the brain and liver of mice after oral administration of arsenate.

The understanding of the biomethylation process of arsenic is essential to uncover the mechanisms of arsenic toxicity. This work analyzes the time course of arsenic species in the brain and liver of adult mice, after a single oral administration of three arsenate doses [2.5, 5.0 and 10 mg As(V)/kg]. Quantification of arsenic species was performed by means of liquid chromatography coupled to atomic fluorescence 2, 5, 8, 12 and 24 h after administration. The results show that 2 h after arsenate administration inorganic arsenic arrives to the liver and its concentration diminishes gradually until becoming non-detectable at 12 h. Arsenic takes longer to appear in the brain and it is present only as dimethyl arsinic acid. Since arsenic concentration decreases in liver while it increases in the brain, this suggests that the arsenic metabolite reaches the brain after formation in the liver. Importantly, the fact that dimethyl arsinic acid is no longer present after 24 h suggests the existence of a mechanism to clear this metabolite from brain tissue.

Conditioned flavor aversion and brain Fos expression following exposure to arsenic.

Recent advances in the knowledge of the cellular effects of arsenic have provided insights into the molecular mechanisms of arsenic-associated carcinogenesis, immunotoxicity and cardiovascular disease. In the present experiments we tested the hypothesis that the arrival of arsenic to the gastrointestinal (GI) tract is detected by the gut-brain axis, which includes hindbrain and forebrain nuclei activated by GI stimulation. As a marker of neuronal activation we measured Fos expression using immunohistochemistry. Because Fos expression in these nuclei is closely linked to the development of conditioned flavor aversion (CFA) we also tested the effect of arsenic on CFA. Our experiments indicate that arsenic ingestion is readily detected by the brain, as shown by increased Fos expression after oral administration of arsenic. Furthermore, the vagus nerve, which supplies information from the GI tract to the brain, is not involved in this response because a complete subdiaphragmatic vagotomy did not reduce the effect of arsenic on brain Fos expression, but enhanced this response. In parallel, arsenic ingestion is associated with a robust, dose-dependent CFA, which started at doses as low as 0.1 mg/kg body weight. In summary, these data indicate that arsenic given by oral administration is detected by the brain in low concentrations, and activates specific nuclei, which might trigger behavioral responses, such as CFA.

Arsenic affects expression and processing of amyloid precursor protein (APP) in primary neuronal cells overexpressing the Swedish mutation of human APP.

Arsenic poisoning due to contaminated water and soil, mining waste, glass manufacture, select agrochemicals, as well as sea food, affects millions of people world wide. Recently, an involvement of arsenic in Alzheimer's disease (AD) has been hypothesized (Gong and O'Bryant, 2010). The present study stresses the hypothesis whether sodium arsenite, and its main metabolite, dimethylarsinic acid (DMA), may affect expression and processing of the amyloid precursor protein (APP), using the cholinergic cell line SN56.B5.G4 and primary neuronal cells overexpressing the Swedish mutation of APP, as experimental approaches. Exposure of cholinergic SN56.B5.G4 cells with either sodium arsenite or DMA decreased cell viability in a concentration- and exposure-time dependent manner, and affected the activities of the cholinergic enzymes acetylcholinesterase and choline acetyltransferase. Both sodium arsenite and DMA exposure of SN56.B5.G4 cells resulted in enhanced level of APP, and sAPP in the membrane and cytosolic fractions, respectively. To reveal any effect of arsenic on APP processing, the amounts of APP cleavage products, sAPPß, and ß-amyloid (Aß) peptides, released into the culture medium of primary neuronal cells derived from transgenic Tg2576 mice, were assessed by ELISA. Following exposure of neuronal cells by sodium arsenite for 12h, the membrane-bound APP level was enhanced, the amount of sAPPß released into the culture medium was slightly higher, while the levels of Aß peptides in the culture medium were considerably lower as compared to that assayed in the absence of any drug. The sodium arsenite-induced reduction of Aß formation suggests an inhibition of the APP γ-cleavage step by arsenite. In contrast, DMA exposure of neuronal cells considerably increased formation of Aß and sAPPß, accompanied by enhanced membrane APP level. The DMA-induced changes in APP processing may be the result of the enhanced APP expression. Alternatively, increased Aß production may also be due to stimulation of caspase activity by arsenic compounds, or failure in Aß degradation. In summary, the present report clearly demonstrates that sodium arsenite and DMA affect processing of APP in vitro.