Contributions for microgrids dynamic modelling and operation

Tese de doutoramento. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 200

Biophysical mechanisms of frequency-dependence and its neuromodulation in neurons in oscillatory networks

In response to oscillatory input, many isolated neurons exhibit a preferred frequency response in their voltage amplitude and phase shift. Membrane potential resonance (MPR), a maximum amplitude in a neuron’s input impedance at a non-zero frequency, captures the essential subthreshold properties of a neuron, which may provide a coordinating mechanism for organizing the activity of oscillatory neuronal networks around a given frequency. In the pyloric central pattern generator network of the crab Cancer borealis, for example, the pacemaker group pyloric dilator neurons show MPR at a frequency that is correlated with the network frequency. This dissertation uses the crab pyloric CPG to examine how, in one neuron type, interactions of ionic currents, even when expressed at different levels, can produce consistent MPR properties, how MPR properties are modified by neuromodulators and how such modifications may lead to distinct functional effects at different network frequencies. In the first part of this dissertation it is demonstrated that, despite the extensive variability of individual ionic currents in a neuron type such as PD, these currents can generate a consistent impedance profile as a function of input frequency and therefore result in stable MPR properties. Correlated changes in ionic current parameters are associated with the dependence of MPR on the membrane potential range. Synaptic inputs or neuromodulators that shift the membrane potential range can modify the interaction of multiple resonant currents and therefore shift the MPR frequency. Neuromodulators change the properties of voltage-dependent ionic currents. Since ionic current interactions are nonlinear, the modulation of excitability and the impedance profile may depend on all ionic current types expressed by the neuron. MPR is generated by the interaction of positive and negative feedback effects due to fast amplifying and slower resonant currents. Neuromodulators can modify existing MPR properties to generate antiresonance (a minimum amplitude response). In the second part of this dissertation, it is shown that the neuropeptide proctolin produces antiresonance in the follower lateral pyloric neuron, but not in the PD neuron. This finding is inconsistent with the known influences of proctolin. However, a novel proctolin-activated ionic current is shown to produce the antiresonance. Using linear models, antiresonance is then demonstrated to amplify MPR in synaptic partner neurons, indicating a potential function in the pyloric network. Neuromodulators are state dependent, so that their action may depend on the prior activity history of the network. It is shown that state-dependence may arise in part from the time-dependence of an inactivating inward current targeted by the neuromodulator proctolin. Due to the kinetics of inactivation, this current advances the burst phase and increases the duty cycle of the neuron, but mainly at higher network frequencies. These results demonstrate that the effect of neuromodulators on MPR in individual neuron types depends on the nonlinear interaction of modulator-activated and other ionic currents as well as the activation of currents with frequency-dependent properties. Consequently, the action of neuromodulators on the output of oscillatory networks may depend on the frequency of oscillations and be predictable from the MPR properties of the network neurons

OPTIMIZATION OF TIME-RESPONSE AND AMPLIFICATION FEATURES OF EGOTs FOR NEUROPHYSIOLOGICAL APPLICATIONS

In device engineering, basic neuron-to-neuron communication has recently inspired the development of increasingly structured and efficient brain-mimicking setups in which the information flow can be processed with strategies resembling physiological ones. This is possible thanks to the use of organic neuromorphic devices, which can share the same electrolytic medium and adjust reciprocal connection weights according to temporal features of the input signals. In a parallel - although conceptually deeply interconnected - fashion, device engineers are directing their efforts towards novel tools to interface the brain and to decipher its signalling strategies. This led to several technological advances which allow scientists to transduce brain activity and, piece by piece, to create a detailed map of its functions. This effort extends over a wide spectrum of length-scales, zooming out from neuron-to-neuron communication up to global activity of neural populations. Both these scientific endeavours, namely mimicking neural communication and transducing brain activity, can benefit from the technology of Electrolyte-Gated Organic Transistors (EGOTs). Electrolyte-Gated Organic Transistors (EGOTs) are low-power electronic devices that functionally integrate the electrolytic environment through the exploitation of organic mixed ionic-electronic conductors. This enables the conversion of ionic signals into electronic ones, making such architectures ideal building blocks for neuroelectronics. This has driven extensive scientific and technological investigation on EGOTs. Such devices have been successfully demonstrated both as transducers and amplifiers of electrophysiological activity and as neuromorphic units. These promising results arise from the fact that EGOTs are active devices, which widely extend their applicability window over the capabilities of passive electronics (i.e. electrodes) but pose major integration hurdles. Being transistors, EGOTs need two driving voltages to be operated. If, on the one hand, the presence of two voltages becomes an advantage for the modulation of the device response (e.g. for devising EGOT-based neuromorphic circuitry), on the other hand it can become detrimental in brain interfaces, since it may result in a non-null bias directly applied on the brain. If such voltage exceeds the electrochemical stability window of water, undesired faradic reactions may lead to critical tissue and/or device damage. This work addresses EGOTs applications in neuroelectronics from the above-described dual perspective, spanning from neuromorphic device engineering to in vivo brain-device interfaces implementation. The advantages of using three-terminal architectures for neuromorphic devices, achieving reversible fine-tuning of their response plasticity, are highlighted. Jointly, the possibility of obtaining a multilevel memory unit by acting on the gate potential is discussed. Additionally, a novel mode of operation for EGOTs is introduced, enabling full retention of amplification capability while, at the same time, avoiding the application of a bias in the brain. Starting on these premises, a novel set of ultra-conformable active micro-epicortical arrays is presented, which fully integrate in situ fabricated EGOT recording sites onto medical-grade polyimide substrates. Finally, a whole organic circuitry for signal processing is presented, exploiting ad-hoc designed organic passive components coupled with EGOT devices. This unprecedented approach provides the possibility to sort complex signals into their constitutive frequency components in real time, thereby delineating innovative strategies to devise organic-based functional building-blocks for brain-machine interfaces.Nell’ingegneria elettronica, la comunicazione di base tra neuroni ha recentemente ispirato lo sviluppo di configurazioni sempre più articolate ed efficienti che imitano il cervello, in cui il flusso di informazioni può essere elaborato con strategie simili a quelle fisiologiche. Ciò è reso possibile grazie all'uso di dispositivi neuromorfici organici, che possono condividere lo stesso mezzo elettrolitico e regolare i pesi delle connessioni reciproche in base alle caratteristiche temporali dei segnali in ingresso. In modo parallelo, gli ingegneri elettronici stanno dirigendo i loro sforzi verso nuovi strumenti per interfacciare il cervello e decifrare le sue strategie di comunicazione. Si è giunti così a diversi progressi tecnologici che consentono agli scienziati di trasdurre l'attività cerebrale e, pezzo per pezzo, di creare una mappa dettagliata delle sue funzioni. Entrambi questi ambiti scientifici, ovvero imitare la comunicazione neurale e trasdurre l'attività cerebrale, possono trarre vantaggio dalla tecnologia dei transistor organici a base elettrolitica (EGOT). I transistor organici a base elettrolitica (EGOT) sono dispositivi elettronici a bassa potenza che integrano funzionalmente l'ambiente elettrolitico attraverso lo sfruttamento di conduttori organici misti ionici-elettronici, i quali consentono di convertire i segnali ionici in segnali elettronici, rendendo tali dispositivi ideali per la neuroelettronica. Gli EGOT sono stati dimostrati con successo sia come trasduttori e amplificatori dell'attività elettrofisiologica e sia come unità neuromorfiche. Tali risultati derivano dal fatto che gli EGOT sono dispositivi attivi, al contrario dell'elettronica passiva (ad esempio gli elettrodi), ma pongono comunque qualche ostacolo alla loro integrazione in ambiente biologico. In quanto transistor, gli EGOT necessitano l'applicazione di due tensioni tra i suoi terminali. Se, da un lato, la presenza di due tensioni diventa un vantaggio per la modulazione della risposta del dispositivo (ad esempio, per l'ideazione di circuiti neuromorfici basati su EGOT), dall'altro può diventare dannosa quando gli EGOT vengono adoperati come sito di registrazione nelle interfacce cerebrali, poiché una tensione non nulla può essere applicata direttamente al cervello. Se tale tensione supera la finestra di stabilità elettrochimica dell'acqua, reazioni faradiche indesiderate possono manifestarsi, le quali potrebbero danneggiare i tessuti e/o il dispositivo. Questo lavoro affronta le applicazioni degli EGOT nella neuroelettronica dalla duplice prospettiva sopra descritta: ingegnerizzazione neuromorfica ed implementazione come interfacce neurali in applicazioni in vivo. Vengono evidenziati i vantaggi dell'utilizzo di architetture a tre terminali per i dispositivi neuromorfici, ottenendo una regolazione reversibile della loro plasticità di risposta. Si discute inoltre la possibilità di ottenere un'unità di memoria multilivello agendo sul potenziale di gate. Viene introdotta una nuova modalità di funzionamento per gli EGOT, che consente di mantenere la capacità di amplificazione e, allo stesso tempo, di evitare l'applicazione di una tensione all’interfaccia cervello-dispositivo. Partendo da queste premesse, viene presentata una nuova serie di array micro-epicorticali ultra-conformabili, che integrano completamente i siti di registrazione EGOT fabbricati in situ su substrati di poliimmide. Infine, viene proposto un circuito organico per l'elaborazione del segnale, sfruttando componenti passivi organici progettati ad hoc e accoppiati a dispositivi EGOT. Questo approccio senza precedenti offre la possibilità di filtrare e scomporre segnali complessi nelle loro componenti di frequenza costitutive in tempo reale, delineando così strategie innovative per concepire blocchi funzionali a base organica per le interfacce cervello-macchina

Analytical Modeling of a Communication Channel Based on Subthreshold Stimulation of Neurobiological Networks

The emergence of wearable and implantable machines manufactured artificially or synthesized biologically opens up a new horizon for patient-centered health services such as medical treatment, health monitoring, and rehabilitation with minimized costs and maximized popularity when provided remotely via the Internet. In particular, a swarm of machines at the scale of a single cell down to the nanoscale can be deployed in the body by the non-invasive or minimally invasive operation (e.g., swallowing and injection respectively) to perform various tasks. However, an individual machine is only able to perform basic tasks so it needs to exchange data with the others and outside world through an efficient and reliable communication infrastructure to coordinate and aggregate their functionalities. We introduce in this thesis Neuronal Communication (NC) as a novel paradigm for utilizing the nervous system \emph{in vivo} as a communication medium to transmit artificial data across the body. NC features body-wide communication coverage while it demands zero investment cost on the infrastructure, does not rely on any external energy source, and exposes the body to zero electromagnetic radiation. n addition, unlike many conventional body area networking techniques, NC is able to provide communication among manufactured electronic machines and biologically engineered ones at the same time. We provide a detailed discussion of the theoretical and practical aspects of designing and implementing distinct paradigms of NC. We also discuss NC future perspectives and open challenges. Adviser: Massimiliano Pierobo

A machine learning driven 3D+1D model for efficient characterization of proton exchange membrane fuel cells

The computational demands of 3D continuum models for proton exchange membrane fuel cells remain substantial. One prevalent approach is the hierarchical model combining a 2D/3D flow field with a 1D sub-model for the catalyst layers and membrane. However, existing studies often simplify the 1D domain to a linearized 0D lumped model, potentially resulting in significant errors at high loads. In this study, we present a computationally efficient neural network driven 3D+1D model for proton exchange membrane fuel cells. The 3D sub-model captures transport in the gas channels and gas diffusion layers and is coupled with a 1D electrochemical sub-model for microporous layers, membrane, and catalyst layers. To reduce computational intensity of the full 1D description, a neural network surrogates the 1D electrochemical sub-model for coupling with the 3D domain. Trained by model-generated large synthetic datasets, the neural network achieves root mean square errors of less than 0.2%. The model is validated against experimental results under various relative humidities. It is then employed to investigate the nonlinear distribution of internal states under different operating conditions. With the neural network operating at 0.5% of the computing cost of the 1D sub-model, the hybrid model preserves a detailed and nonlinear representation of the internal fuel cell states while maintaining computational costs comparable to conventional 3D+0D models. The presented hybrid data-driven and physical modeling framework offers high accuracy and computing speed across a broad spectrum of operating conditions, potentially aiding the rapid optimization of both the membrane electrode assembly and the gas channel geometry.</p

Biomedical Sensing and Imaging

This book mainly deals with recent advances in biomedical sensing and imaging. More recently, wearable/smart biosensors and devices, which facilitate diagnostics in a non-clinical setting, have become a hot topic. Combined with machine learning and artificial intelligence, they could revolutionize the biomedical diagnostic field. The aim of this book is to provide a research forum in biomedical sensing and imaging and extend the scientific frontier of this very important and significant biomedical endeavor

Using the Green's function to simplify and understand dendrites

Neurons are endowed with dendrites: tree-like structures that collect and transform inputs. These arborizations are believed to substantially enhance the computational repertoire of neurons. While it has long been known that dendrites are not iso-potential units, only in the last few decades it was shown experimentally that dendritic branches can transform local inputs in a non-linear fashion. This finding led to the subunit hypothesis, which states that within the dendritic tree, inputs arriving in one branch are transformed non-linearly and independently from what happens in other branches. Recent progress in experimental recording techniques shows that this localized dendritic integration contributes to shaping behavior. While it is generally accepted that the dendritic tree induces multiple subunits, many questions remain unanswered. For instance, it is not known how much separation there needs to be between different branches to be able to function as subunits. Consequently, there is no information on how many subunits can coexist along a dendritic arborization. It is also not known what the input-output relation of these subunits would be, or whether these subunits can be modified by input patterns. As a consequence, assessing the effects of dendrites on the workings of networks of neurons remains mere guesswork. During this work, we choose a theory-driven approach to advance our knowledge about dendrites. Theory can help us understand dendrites by deriving accurate, but conceptually simple models of dendrites that still capture their main computational effects. These models can then be analyzed and fully understood, which in turn teaches us how actual dendrites function computationally. Such simple models typically require less computer operations to simulate than highly detailed dendrite models. Hence, they may also increase the speed of network simulations that incorporate dendrites. The Green's function forms the basis for our theory driven approach. We first explored whether it could be used to reduce the cost of simulating dendrite models. One mathematically interesting finding in this regard is that, because this function is defined on a tree graph, the number of equations can be reduced drastically. Nevertheless, we were forced to conclude that reducing dendrites in this way does not yield new information about the subunit hypothesis. We then focused our attention on another way of decomposing the Green's function. We found that the dendrite model obtained in this way reveals much information on the dendritic subunits. In particular, we found that the occurrence of subunits is well predicted by the ratio of input over transfer impedance in dendrites. This allowed us to estimate the number of subunits that can coexist on dendritic trees. We also found that this ratio can be modified by other inputs, in particular shunting conductances, so that the number of subunits on a dendritic tree can be modified dynamically. We finally were able to show that, due to this dynamical increase of the number of subunits, individual branches that would otherwise respond to inputs as a single unit, could become sensitive to different stimulus features. We believe that this model can be implemented in such a way that it simulates dendrites in a highly efficient manner. Thus, after incorporation in standard neural network simulation software, it can substantially improve the accessibility of dendritic network simulations to modelers