Accurate, Very Low Computational Complexity Spike Sorting Using Unsupervised Matched Subspace Learning

This paper presents an adaptable dictionary-based feature extraction approach for spike sorting offering high accuracy and low computational complexity for implantable applications. It extracts and learns identifiable features from evolving subspaces through matched unsupervised subspace filtering. To provide compatibility with the strict constraints in implantable devices such as the chip area and power budget, the dictionary contains arrays of {-1, 0 and 1} and the algorithm need only process addition and subtraction operations. Three types of such dictionary were considered. To quantify and compare the performance of the resulting three feature extractors with existing systems, a neural signal simulator based on several different libraries was developed. For noise levels $\sigma_N$ between 0.05 and 0.3 and groups of 3 to 6 clusters, all three feature extractors provide robust high performance with average classification errors of less than 8% over five iterations, each consisting of 100 generated data segments. To our knowledge, the proposed adaptive feature extractors are the first able to classify reliably 6 clusters for implantable applications. An ASIC implementation of the best performing dictionary-based feature extractor was synthesized in a 65-nm CMOS process. It occupies an area of 0.09 mm2 and dissipates up to about 10.48 μW from a 1 V supply voltage, when operating with 8-bit resolution at 30 kHz operating frequency

Prader Willi locus Snord116 RNA regulates hypothalamic functions: sleep and temperature

Sleep is a complex behavior and it is hierarchically regulated involving several brain regions, neurotransmitters, and genes that co-operate in building modulatory mechanisms aimed at controlling and maintaining sleep. Specifically, this thesis attempts to address/understand how genomic imprinting, which affect a subset of genes in mammals resulting in a monoallelic expression, may regulate sleep. One of the main brain regions involved in sleep regulation is the hypothalamus. Within the hypothalamic region imprinted genes are highly expressed. Interestingly, it has been described that hypothalamic insufficiency caused by lack of paternal expression of chromosome 15q11- q13, leads to Prader-Willi syndrome (PWS). Specifically, the microdeletion of the small nuclear ribonucleic acid (RNA)-116 (SNORD116) cluster within the PWS locus plays a major role in developing the main endophenotypes that characterize this syndrome (i.e. REM sleep dysfunction, hyperphagia and temperature instability). However, what could be the role of the paternally imprinted gene Snord116 in the hypothalamic function is unknown. Additionally, is still unclear the specific contribution of the Snord116 gene in developing the PWS symptoms. Since these unresolved points my research has been split into three parts: In the first part of this research, it has been shown that the paternally imprinted gene Snord116 plays a crucial role in the formation and organization of the orexin (OX) and melanin concentrating hormone (MCH) systems, the two main neuro-modulatory systems within the lateral hypothalamus (LH). Moreover, a compromised neuronal dynamic in the LH and a sleep- wake regulation of mice with paternal deletion of Snord116 (PWScrm+/p-) is observed. This abnormal neuronal dynamic is accompanied by a significant reduction in OX neurons in the LH of mutant mice. For this reason, it is proposed that the dysregulation of rapid eye movement (REM) sleep, food intake and temperature control observed in PWS mice are potentially due to this imbalance between OX- and MCH-expressing neurons in the LH as observed in mutant mice. In the second part of this research, it has been investigated the microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles during non-REM sleep. Indeed, REM sleep is thought to contribute to neuronal network formation early in brain development, while spindles are markers of thalamocortical processes. In neurodevelopmental disorders both sleep structures (REM and sleep spindles) are often compromised and this influence functional properties of cortical neurons. These results indicate 1 that REM sleep properties and its occurrence (REM sleep episodes classified as short-and long REM sleep episode) throughout the sleep-wake cycles are selectively influenced by the Snord116 gene in mice. Moreover, the specific abnormalities in sleep spindles in PWS model systems, indicate that these sleep features may be translated as potential biomarkers in human PWS sufferers. In the third part of this research, it has been proposed a new therapeutic approach for PWS patients aiming to ameliorate the sleep phenotypes that significantly compromise the quality of life of these patients. Pitolisant (a wake-promoting drug) was orally administrated in mice carrying the paternal deletion of the Snord116 gene that are affected by REM sleep alteration coupled with a reduction of the OX neurons. Overall the results of this research show that Pitolisant ameliorates the REM sleep alteration in these mice, although other studies are needed to clarify whether this drug may be easily translated/used in clinics. In conclusion, this thesis provides support for the important role of Snord116 in the regulation of REM sleep and its propensity and its regulatory mechanisms in the hypothalamus. Finally, a new pharmacological approach for PWS by using Pitolisant has been proposed to ameliorate the sleep alteration that significantly affects the PWS patients

De animais a máquinas : humanos tecnicamente melhores nos imaginários de futuro da convergência tecnológica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Sociologia, 2020.O tema desta investigação é discutir os imaginários sociais de ciência e tecnologia que emergem a partir da área da neuroengenharia, em sua relação com a Convergência Tecnológica de quatro disciplinas: Nanotecnologia, Biotecnologia, tecnologias da Informação e tecnologias Cognitivas - neurociências- (CT-NBIC). Estas áreas desenvolvem-se e são articuladas por meio de discursos que ressaltam o aprimoramento das capacidades físicas e cognitivas dos seres humanos, com o intuito de construir uma sociedade melhor por meio do progresso científico e tecnológico, nos limites das agendas de pesquisa e desenvolvimento (P&D). Objetivos: Os objetivos nesse cenário, são discutir as implicações éticas, econômicas, políticas e sociais deste modelo de sistema sociotécnico. Nos referimos, tanto as aplicações tecnológicas, quanto as consequências das mesmas na formação dos imaginários sociais, que tipo de relações se estabelecem e como são criadas dentro desse contexto. Conclusão: Concluímos na busca por refletir criticamente sobre as propostas de aprimoramento humano mediado pela tecnologia, que surgem enquanto parte da agenda da Convergência Tecnológica NBIC. No entanto, as propostas de melhoramento humano vão muito além de uma agenda de investigação. Há todo um quadro de referências filosóficas e políticas que defendem o aprimoramento da espécie, vertentes estas que se aliam a movimentos trans-humanistas e pós- humanistas, posições que são ao mesmo tempo éticas, políticas e econômicas. A partir de nossa análise, entendemos que ciência, tecnologia e política estão articuladas, em coprodução, em relação às expectativas de futuros que são esperados ou desejados. Ainda assim, acreditamos que há um espaço de diálogo possível, a partir do qual buscamos abrir propostas para o debate público sobre questões de ciência e tecnologia relacionadas ao aprimoramento da espécie humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The subject of this research is to discuss the social imaginaries of science and technology that emerge from the area of neuroengineering in relation with the Technological Convergence of four disciplines: Nanotechnology, Biotechnology, Information technologies and Cognitive technologies -neurosciences- (CT-NBIC). These areas are developed and articulated through discourses that emphasize the enhancement of human physical and cognitive capacities, the intuition it is to build a better society, through the scientific and technological progress, at the limits of the research and development (R&D) agendas. Objectives: The objective in this scenery, is to discuss the ethic, economic, politic and social implications of this model of sociotechnical system. We refer about the technological applications and the consequences of them in the formation of social imaginaries as well as the kind of social relations that are created and established in this context. Conclusion: We conclude looking for critical reflections about the proposals of human enhancement mediated by the technology. That appear as a part of the NBIC technologies agenda. Even so, the proposals of human enhancement go beyond boundaries that an investigation agenda. There is a frame of philosophical and political references that defend the enhancement of the human beings. These currents that ally to the transhumanism and posthumanism movements, positions that are ethic, politic and economic at the same time. From our analysis, we understand that science, technology and politics are articulated, are in co-production, regarding the expected and desired futures. Even so, we believe that there is a space of possible dialog, from which we look to open proposals for the public discussion on questions of science and technology related to enhancement of human beings