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Agir de façon optimale dans un environnement incertain nécessite d'évaluer et de comparer les coûts et bénéfices des différentes alternatives. Cela implique aussi de réguler et de contrôler le comportement de façon flexible pour optimiser les périodes de recherche de gains ou de ressources et les périodes d'exploitation des acquis. Une des hypothèses actuelles sur les mécanismes neurobiologiques impliqués, propose que cortex cingulaire antérieur (CCA), associé à l’évaluation de l’action, et cortex préfrontal dorsolatéral (CPFdl), associé au contrôle cognitif, interagiraient pour réguler le comportement. Les travaux réalisés au cours de cette thèse ont permis de préciser le rôle joué par le CCA dans la détection et l’évaluation des performances ainsi que ses interactions avec le CPFdl au sein d'une boucle du contrôle cognitif. Menés grâce à des enregistrements électrophysiologiques chez le singe en comportement, ils apportent des précisions sur la séquence d’activation du CCA et du CPFdl dans la bande de fréquences gamma lors de l'adaptation du comportement. L’étude des potentiels de champs locaux de ces deux régions amènent à poser des hypothèses sur les mécanismes oscillatoires sous-jacents et notamment sur le rôle des communications basses fréquences entre le CCA et le CPFdl et leur implication différentielle entre recherche et exploitation. / Acting optimally in uncertain environments requires evaluating costs and benefits of choosing each alternative. It also requires to flexibly regulate between exploration for and exploitation of resources. One current hypothesis is that the anterior cingulate cortex (ACC), involved in action valuation, and dorsolateral prefrontal cortex (dlPFC), involved in cognitive control, interact to elaborate an optimal regulation of behaviour. Studies achieved during this thesis allowed to precise the role of ACC in the detection and valuation of action outcomes as well as to describe the interactions with dlPFC in a cognitive control loop. Thanks to neurophysiological recordings in behaving monkey our work give new clues on the sequential activation of ACC and dlPFC during adaptation. The analyses of local field potentials allowed us to suggest hypotheses on the underlying oscillatory mechanisms, in particular on low frequency communications between ACC and dlPFC, and their modulation during exploration and exploitation.

O greening ou Huanglongbing (HLB) é uma das mais graves doenças dos citros presentes nos pomares do Brasil. Causada pela bactéria Candidatus Liberibacter spp, é transmitida pelo inseto psilídeo Diaphorina citri, que ao se alimentar de uma planta doente transmite a doença às demais plantas. O greening apresenta como sintoma, manchas amareladas nas folhas, muitas vezes confundidas com deficiências nutricionais. A erradicação da planta e o controle do inseto transmissor são as únicas formas de prevenção para evitar a sua propagação. Este trabalho teve por objetivo avaliar uma metodologia baseada em segmentação por cor e outra baseada em análise de textura para avaliação de folhas de citros sintomáticas, identificando se estão contaminadas com o greening ou outras doenças e deficiências nutricionais. Foram fornecidas pelo grupo FISHER, 324 amostras de folhas cítricas, contendo folhas com doenças (greening, CVC e rubelose) e deficiências nutricionais (manganês, magnésio e zinco). As folhas foram digitalizadas por um scanner de mesa, com duas resoluções, utilizando somente a parte frontal da folha. Foram montados três bancos de imagens. Os resultados gerados com a metodologia baseada em segmentação por cor utilizando RNA PMC, mostraram que essa metodologia não é eficiente. Na metodologia baseada na análise por textura foram avaliados os descritores LBP, LFP e os de Haralick. Para estes descritores foram extraídas amostras por folha e por quadrantes das folhas nos canais de cores vermelho e verde e amostras em níveis de cinza. Os resultados gerados pelos descritores foram classificados pela distância &#9672 e pelos algoritmos IBK e RNA PMC do toolbox Weka. Os melhores resultados foram para os descritores LBP e LFP-s para distância &#9672, com valores de sensibilidade acima de 97% e 93%, respectivamente, e para o LBP com o algoritmo IBK, com valores de sensibilidade acima de 98,5%. Os resultados obtidos evidenciam que o descritor LBP é o mais eficiente seguido pelo LFP-s na diferenciação do greening das outras pragas. / The greening or Huanglongbing (HLB) is one of the most serious diseases of citrus orchards present in Brazil. HLB is caused by the bacterium Candidatus Liberibacter spp, it is transmitted by the psyllid insect (Diaphorina citri) that, when feeding on a diseased plant, it transmits the disease to other plants. One of the symptoms of the greening are yellowish spots on the leaves, often confused with nutritional deficiencies. The eradication of plants and control of insect are the only forms of prevention. This work aims to evaluate two methodologies: one based on color segmentation and the other based on texture analysis for assessment of symptomatic citrus leaves, identifying whether they are infected with greening and other diseases and nutritional deficiencies. A number of 324 samples of citrus leaves were provided by FISHER group, infected with diseases (greening, CVC, rubelose) and nutritional deficiencies ( manganese, magnesium, zinc) . The leaves were acquired by a flatbed scanner with two different resolutions, using only the front side of the leaf. Three datasets of images were constructed. The results generated using the methodology based on color segmentation with ANN MLP, showed that this methodology is not efficient. In the methodology based on texture analysis it was evaluated the LBP, LFP and the Haralick descriptors. For these descriptors it was extracted samples from the leaves and quadrants of leaves, in red and green color channels and grayscale. The results generated by the descriptors were classified by &#9672 distance and the algorithms IBK and ANN MLP from the toolbox Weka. The best results were for LBP descriptor and LFP-s for &#9672 distance with values of sensitivity above 97% and 93%, respectively, and the LBP with IBK algorithm, with values of sensitivity above 98.5%. The results showed that the LBP descriptor is the most efficient followed by LFP-s in the differentiation of the greening from other pests.

Técnicas biométricas procuraram identificar usuários pela textura da íris, impressão digital, traços faciais, entre outros. A íris humana apresenta características de textura que a classificam como uma peculiaridade biométrica de grande poder de discriminação no reconhecimento de pessoas. O objetivo deste trabalho é avaliar a eficiência de uma nova metodologia de análise de texturas em desenvolvimento no LAVI (Laboratório de Visão Computacional da EESC-USP) na identificação de indivíduos por meio da textura de sua íris. A metodologia denomina-se Local Fuzzy Pattern e tem sido utilizada com excelente desempenho com texturas gerais, naturais e artificiais. Este documento detalha as técnicas utilizadas para extração e normalização da textura da íris, a utilização e os resultados obtidos com o método Local Fuzzy Pattern aplicado à classificação biométrica da íris humana. Os resultados obtidos apresentam sensibilidade de até 99,7516% com a aplicação da metodologia proposta em bancos de imagens de íris humana disponíveis na internet demonstram a viabilidade da técnica proposta. / Biometric techniques sought to identify users by the texture of the iris, fingerprint, facial features, among others. The human iris have texture characteristics that rank it as a powerful biometric peculiarity on human recognition. The objective of this masters proposal is to investigate the efficiency of a new methodology of iris texture analysis currently in development in LAVI (Laboratório de Visão Computacional da EESC-USP). The methodology is called LFP (Local Fuzzy Pattern) and has been used with excellent overall performance on artificial and natural textures. This document details the techniques used for the extraction and normalization of the iris texture, the use and results of the local fuzzy pattern method applied to biometric classification of the human eye. The results show a sensibility of value up to 99.7516%, obtained by applying the proposed methodology on human iris photos from image database available on the internet does showing the viability of the technique.

Técnicas biométricas procuraram identificar usuários pela textura da íris, impressão digital, traços faciais, entre outros. A íris humana apresenta características de textura que a classificam como uma peculiaridade biométrica de grande poder de discriminação no reconhecimento de pessoas. O objetivo deste trabalho é avaliar a eficiência de uma nova metodologia de análise de texturas em desenvolvimento no LAVI (Laboratório de Visão Computacional da EESC-USP) na identificação de indivíduos por meio da textura de sua íris. A metodologia denomina-se Local Fuzzy Pattern e tem sido utilizada com excelente desempenho com texturas gerais, naturais e artificiais. Este documento detalha as técnicas utilizadas para extração e normalização da textura da íris, a utilização e os resultados obtidos com o método Local Fuzzy Pattern aplicado à classificação biométrica da íris humana. Os resultados obtidos apresentam sensibilidade de até 99,7516% com a aplicação da metodologia proposta em bancos de imagens de íris humana disponíveis na internet demonstram a viabilidade da técnica proposta. / Biometric techniques sought to identify users by the texture of the iris, fingerprint, facial features, among others. The human iris have texture characteristics that rank it as a powerful biometric peculiarity on human recognition. The objective of this masters proposal is to investigate the efficiency of a new methodology of iris texture analysis currently in development in LAVI (Laboratório de Visão Computacional da EESC-USP). The methodology is called LFP (Local Fuzzy Pattern) and has been used with excellent overall performance on artificial and natural textures. This document details the techniques used for the extraction and normalization of the iris texture, the use and results of the local fuzzy pattern method applied to biometric classification of the human eye. The results show a sensibility of value up to 99.7516%, obtained by applying the proposed methodology on human iris photos from image database available on the internet does showing the viability of the technique.

O greening ou Huanglongbing (HLB) é uma das mais graves doenças dos citros presentes nos pomares do Brasil. Causada pela bactéria Candidatus Liberibacter spp, é transmitida pelo inseto psilídeo Diaphorina citri, que ao se alimentar de uma planta doente transmite a doença às demais plantas. O greening apresenta como sintoma, manchas amareladas nas folhas, muitas vezes confundidas com deficiências nutricionais. A erradicação da planta e o controle do inseto transmissor são as únicas formas de prevenção para evitar a sua propagação. Este trabalho teve por objetivo avaliar uma metodologia baseada em segmentação por cor e outra baseada em análise de textura para avaliação de folhas de citros sintomáticas, identificando se estão contaminadas com o greening ou outras doenças e deficiências nutricionais. Foram fornecidas pelo grupo FISHER, 324 amostras de folhas cítricas, contendo folhas com doenças (greening, CVC e rubelose) e deficiências nutricionais (manganês, magnésio e zinco). As folhas foram digitalizadas por um scanner de mesa, com duas resoluções, utilizando somente a parte frontal da folha. Foram montados três bancos de imagens. Os resultados gerados com a metodologia baseada em segmentação por cor utilizando RNA PMC, mostraram que essa metodologia não é eficiente. Na metodologia baseada na análise por textura foram avaliados os descritores LBP, LFP e os de Haralick. Para estes descritores foram extraídas amostras por folha e por quadrantes das folhas nos canais de cores vermelho e verde e amostras em níveis de cinza. Os resultados gerados pelos descritores foram classificados pela distância &#9672 e pelos algoritmos IBK e RNA PMC do toolbox Weka. Os melhores resultados foram para os descritores LBP e LFP-s para distância &#9672, com valores de sensibilidade acima de 97% e 93%, respectivamente, e para o LBP com o algoritmo IBK, com valores de sensibilidade acima de 98,5%. Os resultados obtidos evidenciam que o descritor LBP é o mais eficiente seguido pelo LFP-s na diferenciação do greening das outras pragas. / The greening or Huanglongbing (HLB) is one of the most serious diseases of citrus orchards present in Brazil. HLB is caused by the bacterium Candidatus Liberibacter spp, it is transmitted by the psyllid insect (Diaphorina citri) that, when feeding on a diseased plant, it transmits the disease to other plants. One of the symptoms of the greening are yellowish spots on the leaves, often confused with nutritional deficiencies. The eradication of plants and control of insect are the only forms of prevention. This work aims to evaluate two methodologies: one based on color segmentation and the other based on texture analysis for assessment of symptomatic citrus leaves, identifying whether they are infected with greening and other diseases and nutritional deficiencies. A number of 324 samples of citrus leaves were provided by FISHER group, infected with diseases (greening, CVC, rubelose) and nutritional deficiencies ( manganese, magnesium, zinc) . The leaves were acquired by a flatbed scanner with two different resolutions, using only the front side of the leaf. Three datasets of images were constructed. The results generated using the methodology based on color segmentation with ANN MLP, showed that this methodology is not efficient. In the methodology based on texture analysis it was evaluated the LBP, LFP and the Haralick descriptors. For these descriptors it was extracted samples from the leaves and quadrants of leaves, in red and green color channels and grayscale. The results generated by the descriptors were classified by &#9672 distance and the algorithms IBK and ANN MLP from the toolbox Weka. The best results were for LBP descriptor and LFP-s for &#9672 distance with values of sensitivity above 97% and 93%, respectively, and the LBP with IBK algorithm, with values of sensitivity above 98.5%. The results showed that the LBP descriptor is the most efficient followed by LFP-s in the differentiation of the greening from other pests.

Le cerveau est composé de réseaux de neurones interconnectés dont la mise en place au cours du développement cérébral est hautement régulée par des processus cellulaires, moléculaires et fonctionnels. Un dysfonctionnement de ces processus peut perturber l’établissement de ces réseaux et conduire à des pathologies neurologiques. L’épilepsie absence est une pathologie génétiquement déterminée qui apparait au cours de l’enfance. Les crises d’absences sont caractérisées par une altération de la conscience et par la présence de décharges de pointe-ondes (DPO) sur l’électroencéphalogramme initiées au sein d’un zone restreinte du cortex. Cependant, on sait peu de choses sur les mécanismes conduisant à la mise en place des décharges épileptiques récurrentes au cours de l’enfance (i.e. l’épileptogenèse). Nous avons fait l’hypothèse que des anomalies du processus de maturation cérébrale sont à l’origine de l’apparition des DPO.J’ai vérifié cette hypothèse chez un modèle génétique d’épilepsie absence, le rat GAERS. Dans un premier temps, j’ai étudié l’épileptogenèse du GAERS grâce à l’enregistrement in vivo du potentiel de champs local et de l’activité intracellulaire des neurones pyramidaux au niveau du site d’initiation des DPO, le cortex somatosensoriel (SoCX). Nous avons mis en évidence que les DPO se développent progressivement après la fin d’une période de maturation hautement sensible et malléable du SoCx (i.e. période critique). La maturation des décharges épileptiques consiste en une augmentation de leur fréquence, de leur durée et en l’évolution du motif de décharge jusqu’à l’âge adulte, période à laquelle ces paramètres atteignent une relative stabilité. De plus, ces changements sont associés à une altération graduelle des propriétés intrinsèques des neurones pyramidaux qui s’accompagne d’une augmentation progressive de la force de l’activité synaptique locale et d’une propension accrue des neurones du SoCx à générer des oscillations synchrones.Nous avons ensuite recherché les raisons de cette prédisposition anormale des neurones du SoCx à se synchroniser chez le GAERS. Dans ce but, nous avons cherché à mettre en évidence des anomalies de la maturation corticale au niveau de la structure et de l’organisation fonctionnelle du SoCx avant l’apparition des DPO. En combinant l’IRM, des marquages immunohistochimiques et le traçage rétrograde monosynaptique des connexions longue distance par le virus de la rage modifié, nous avons pu montrer qu’aucune anomalie globale du cerveau et du SoCx n’est présente chez le GAERS avant l’apparition des DPO. Afin de déterminer la présence d’anomalies fonctionnelles nous avons utilisé l’imagerie calcique biphoton et enregistré in vivo la dynamique de l’activité spontanée du réseau de neurones des couches 2-3 du SoCx. Chez le GAERS, nous avons mis en évidence que ces neurones sont plus actifs et dévoilent une organisation fonctionnelle différente de celle des animaux contrôles. Enfin, pour comprendre comment cette organisation fonctionnelle anormale est médiée, nous avons étudié la structure dendritique et synaptique du SoCx en combinant la microscopie électronique et la reconstruction morphologique de neurones. Nous avons mis en évidence un élargissement des épines dendritiques associé à un allongement de la densité post-synaptique au sein du SoCx chez le GAERS.L’ensemble de ces résultats démontrent la nature progressive du développement de l’épilepsie absence ainsi que l’existence d’anomalies de la maturation corticale qui affectent la structure et la fonction du réseau neuronal, avant l’apparition des crises épileptiques. Ces altérations constituent une prédisposition à l’établissement et l’évolution des DPO et sont une cible thérapeutique potentielle qui pourrait permettre de bloquer la mise en place des crises d’absences. / The brain is organized into several interconnected neuronal networks whose formation is highly regulated by cellular, molecular and functional processes. The dysfunction of these processes during brain development could disrupt neuronal circuit establishment and lead to neurological pathologies. Absence epilepsy is a genetically determined disease with a childhood onset. Absence seizures are characterized by an impairment of the consciousness associated on the electroencephalogram with spike and wave discharges (SWD). However, little is known about the mechanisms leading to the establishment of recurrent epileptic discharges (i.e. epileptogenesis). We hypothesized that SWD onset originates from an abnormal brain maturation.During my PhD, I examined this hypothesis in a recognized genetic model of absence epilepsy, the GAERS rat. First, I studied the epileptogenic process by recording in vivo the local field potential and the intracellular activities of pyramidal neurons in the initiating area of SWD, the somatosensory cortex (SoCx), at different post natal days in GAERS. We showed that SWD progressively developed after the end of a highly sensitive and plastic maturation period of the SoCx (i.e critical period). Afterward, epileptic discharges maturation consists in an increase of their duration, their number and in an evolution of the pattern reaching a relative stability at adulthood. Moreover, these changes are associated with a gradual abnormal alteration of the intrinsic properties of pyramidal neurons which is accompanied with a progressive increase in the strength of the local synaptic activity and a growing propensity of SoCx neurons to generate synchronized oscillations.Then, we explored the reasons for this abnormal susceptibility of SoCx neurons to be more synchronized in GAERS. We sought to bring to light anomalies of SoCx maturation at the structural and functional organization level prior to SWD onset in GAERS. Combining MRI, immunohistochemistry labeling and rabies-mediated retrograde monosynaptic tracing to reveal long-range connectivity, we showed that, prior to SWD onset, no brain and SoCx architecture abnormalities could be observed in GAERS. Then, using two photon calcium imaging we recorded in vivo the spontaneous activity of SoCx layers 2-3 neurons to evidence their functional organization. We found that these neurons were more active and unveiled a different functional organization in GAERS compared to control animals. Finally, to understand how is mediated this abnormal functional organization, we studied the dendritic and synaptic fine structure of SoCx neurons by combining electron microscopy and morphological neuron reconstruction. We highlighted an enlargement of the dendritic spines as well as an increase of the post-synaptic density length in the GAERS SoCx.Taken together, these findings showed the progressive nature of absence epilepsy development and the presence of abnormalities in the cortical maturation which affect the structure and the functional of the neuronal network the prior to SWD. These alterations constitute a breeding ground for the establishment and evolution of SWD. Future studies will aim at interfering with the epileptogenesis process should target these early alterations to stop seizure development.

Different kinds of batteries suit different applications, and consequently several different chemistries exist. In order to better understand the limitations of low temperature performance, a Li-ion battery chemistry normally intended for room temperature use, graphite-Lithium Iron Phosphate, with 1 M LiPF6 ethylene carbonate:diethylene carbonate electrolyte, is here put under testing at -10°C and compared with room temperature cycling performance. Understanding the temperature limitations of this battery chemistry will give better understanding of the desired properties of a substitute using alternative materials. The experimental studies have comprised a combination of battery cycle testing, and surface analysis of the electrodes by Scanning Electron Microscopy and X-Ray Photoelectron Spectroscopy. Results showed that with low enough rate, temperature is less of a problem, but with increased charge rate, there are increasingly severe effects on performance at low temperatures. XPS measurements of low charge rate samples showed similar Solid Electrolyte Interface layers formed on the graphite anode for room- and low temperature batteries, but with indications of a thicker layer on the former. A section of the report handles specific low temperature battery chemistries. The conclusions- and outlook were made by comparing the results found in the study with earlier findings on low temperature Li-ion batteries and present possible approaches for modifying battery performance at lowered temperatures. / I detta projekt har litium-jon-batterier testats i avseende på sina lågtemperaturprestanda. Arbetet gjordes genom att testa och jämföra prestantda mellan prover vid -10°C och rumstemperaturprover. Med analytiska instrument studerades både den morfologiska och kemiska förändring som skett under användning. Vald batterikemi har varit av slaget grafit-litiumjärnfosfat med en typisk organisk elektrolyt. Denna batterikemi är inte på något sätt anpassad för lågtemperaturprestanda och med det hoppas kunna påvisas de effekter som en mer lämpligt lågtemperaturkemi åtgärdar, och förstå hur de gör det. Med låg temperatur uppkommer en större ’tröghet’ för de kemiska reaktioner som sker i ett batteri. Om designen inte är särskilt gjord för låg temperatur kan effekterna bli osäkra, rent av farliga. Risken ökar nämligen för plätering av metalliskt litium på den negativa elektroden, och skulle litiumdeponeringen växa i den riktning som kopplar samman batteriets poler så kortsluts systemet. Med den höga energidensitet som karaktäriserar litium-jon-batterier vore en kortslutning extra beklaglig då den organiska elektrolyten kan antändas, med en potentiell explosion som följd.Inom särskilda applikationer kan lågtemperaturmiljöer förväntas för ett batteri, till exempel för fordon. En elbil i skandinaviskt klimat skulle behöva fungera ohindrat även vintertid, då temperaturerna ofta når -10°C och lägre. Samtidigt får man påminnas om att litium-jon-batterierna är relativt moderna och ännu inte har fått något stort genomslag som framdrivningsmedel. Detta försätter bilindustrin i ett krafigt behov av omfattande forskning för att kunna ta strategiskt sunda beslut för att möjliggöra en ordentlig introducering av elbilar som trovärdig ersättare till de fossilt drivna bilarna. I linje med trenden att ständigt bygga säkrare bilar måste elbilarna kunna visa upp förutsägbarhet, och med detta pålitlighet och säkerhet. I detta arbetet erhölls resultat som visade på batterifunktion även vid den sänkta temperaturen, men med gränser för hur snabbt laddningöverföring kunde ske jämfört med i rumstemperatur. Bevis för bildande av skyddsfilm på anod efter 1.5 battericykler, snarlik komposition för -10°C - och rumstemperaturbatterier – men med vissa indikationer på ett tjockare bildat lager hos den senare. Därtill gjordes jämförelser med specifika lågtemperaturselektrolyter, där en skillnad i framförallt innehåll utav etylkarbonat (mindre andel vid lågtemperaturapplikationer) uppvisar stora förbättringar i kallare klimat. En sådan provblandning gjordes och uppvisade bättre prestanda vid -10°C än rumstemperaturbatterier med standardelektrolyt. Arbetet har utförts vid Institutionen för Kemi-Ångström vid Uppsala universitet.

abstract: Understanding where our bodies are in space is imperative for motor control, particularly for actions such as goal-directed reaching. Multisensory integration is crucial for reducing uncertainty in arm position estimates. This dissertation examines time and frequency-domain correlates of visual-proprioceptive integration during an arm-position maintenance task. Neural recordings were obtained from two different cortical areas as non-human primates performed a center-out reaching task in a virtual reality environment. Following a reach, animals maintained the end-point position of their arm under unimodal (proprioception only) and bimodal (proprioception and vision) conditions. In both areas, time domain and multi-taper spectral analysis methods were used to quantify changes in the spiking, local field potential (LFP), and spike-field coherence during arm-position maintenance. In both areas, individual neurons were classified based on the spectrum of their spiking patterns. A large proportion of cells in the SPL that exhibited sensory condition-specific oscillatory spiking in the beta (13-30Hz) frequency band. Cells in the IPL typically had a more diverse mix of oscillatory and refractory spiking patterns during the task in response to changing sensory condition. Contrary to the assumptions made in many modelling studies, none of the cells exhibited Poisson-spiking statistics in SPL or IPL. Evoked LFPs in both areas exhibited greater effects of target location than visual condition, though the evoked responses in the preferred reach direction were generally suppressed in the bimodal condition relative to the unimodal condition. Significant effects of target location on evoked responses were observed during the movement period of the task well. In the frequency domain, LFP power in both cortical areas was enhanced in the beta band during the position estimation epoch of the task, indicating that LFP beta oscillations may be important for maintaining the ongoing state. This was particularly evident at the population level, with clear increase in alpha and beta power. Differences in spectral power between conditions also became apparent at the population level, with power during bimodal trials being suppressed relative to unimodal. The spike-field coherence showed confounding results in both the SPL and IPL, with no clear correlation between incidence of beta oscillations and significant beta coherence. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2017

Recently-developed technologies for monitoring activity in populations of neurons make it possible for the first time, in principle, to ask many basic questions in neuroscience. However, computational tools for analyzing newly available data need to be developed. The goal of this thesis is to contribute to this effort by focusing on two specific problems. First, we used a point-process regression framework to provide a methodology for statistical assessment of the link between neural spike synchrony and network-wide oscillations. In simulations, we showed that our method can recover ground-truth relationships, and in two types of spike train data we illustrated the kinds of results the method can produce. The approach improves on methods in the literature and may be adapted to many different experimental settings. Second, we considered the problem of source extraction in calcium imaging data, i.e., the detection of neurons within a field of view and the extraction of each neuron’s activity. The data we mainly focus on are recorded with a microendoscope, which has the unique advantage of imaging deep brain regions in freely behaving animals. These data suffer from high levels of background fluorescence, as well as the potential for overlapping neuronal signals. Based on the existing constrained nonnegative matrix factorization (CNMF) framework, we developed an efficient method to process microendoscopic data. Our method utilizes a novel algorithm to initialize the spatial shapes and temporal activity of the neurons from the raw video data independently from the strong fluctuating background. This step ensures the efficiency and accuracy of solving a nonconvex CNMF problem. Our method also models the complicated background by including its low-spatial frequency structure and the locally-low-rank feature to avoid absorbing cellular signals into the background term. We developed a tractable solution to estimate the background activity using this new model. After subtracting the approximated background, we followed the CNMF framework to demix neural signals and recover denoised and deconvolved temporal activity. We optimized several algorithms in solving the CNMF problems to get accurate results. In practice, our method outperforms all existing methods and has been adopted by many experimental labs.