An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials

This document is the Accepted Manuscript version of the following article: Reinoud Maex, ‘An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials’, Neural Computation, March 2018. Under embargo until 22 June 2018. The final, definitive version of this paper is available online at doi: https://doi.org/10.1162/NECO_a_01068. © 2018 Massachusetts Institute of Technology. Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.Recent advances in engineering and signal processing have renewed the interest in invasive and surface brain recordings, yet many features of cortical field potentials remain incompletely understood. In the present computational study, we show that a model circuit of interneurons, coupled via both GABA(A) receptor synapses and electrical synapses, reproduces many essential features of the power spectrum of local field potential (LFP) recordings, such as 1/f power scaling at low frequency (< 10 Hz) , power accumulation in the γ-frequency band (30–100 Hz), and a robust α rhythm in the absence of stimulation. The low-frequency 1/f power scaling depends on strong reciprocal inhibition, whereas the α rhythm is generated by electrical coupling of intrinsically active neurons. As in previous studies, the γ power arises through the amplifica- tion of single-neuron spectral properties, owing to the refractory period, by parameters that favour neuronal synchrony, such as delayed inhibition. The present study also confirms that both synaptic and voltage-gated membrane currents substantially contribute to the LFP, and that high-frequency signals such as action potentials quickly taper off with distance. Given the ubiquity of electrically coupled interneuron circuits in the mammalian brain, they may be major determinants of the recorded potentials.Peer reviewe

Multispectral image analysis in laparoscopy – A machine learning approach to live perfusion monitoring

Modern visceral surgery is often performed through small incisions. Compared to open surgery, these minimally invasive interventions result in smaller scars, fewer complications and a quicker recovery. While to the patients benefit, it has the drawback of limiting the physician’s perception largely to that of visual feedback through a camera mounted on a rod lens: the laparoscope. Conventional laparoscopes are limited by “imitating” the human eye. Multispectral cameras remove this arbitrary restriction of recording only red, green and blue colors. Instead, they capture many specific bands of light. Although these could help characterize important indications such as ischemia and early stage adenoma, the lack of powerful digital image processing prevents realizing the technique’s full potential. The primary objective of this thesis was to pioneer fluent functional multispectral imaging (MSI) in laparoscopy. The main technical obstacles were: (1) The lack of image analysis concepts that provide both high accuracy and speed. (2) Multispectral image recording is slow, typically ranging from seconds to minutes. (3) Obtaining a quantitative ground truth for the measurements is hard or even impossible. To overcome these hurdles and enable functional laparoscopy, for the first time in this field physical models are combined with powerful machine learning techniques. The physical model is employed to create highly accurate simulations, which in turn teach the algorithm to rapidly relate multispectral pixels to underlying functional changes. To reduce the domain shift introduced by learning from simulations, a novel transfer learning approach automatically adapts generic simulations to match almost arbitrary recordings of visceral tissue. In combination with the only available video-rate capable multispectral sensor, the method pioneers fluent perfusion monitoring with MSI. This system was carefully tested in a multistage process, involving in silico quantitative evaluations, tissue phantoms and a porcine study. Clinical applicability was ensured through in-patient recordings in the context of partial nephrectomy; in these, the novel system characterized ischemia live during the intervention. Verified against a fluorescence reference, the results indicate that fluent, non-invasive ischemia detection and monitoring is now possible. In conclusion, this thesis presents the first multispectral laparoscope capable of videorate functional analysis. The system was successfully evaluated in in-patient trials, and future work should be directed towards evaluation of the system in a larger study. Due to the broad applicability and the large potential clinical benefit of the presented functional estimation approach, I am confident the descendants of this system are an integral part of the next generation OR

Pushing the boundaries of photoconductive sampling in solids

The advent of laser-based optical tools featuring few-cycle pulses with durations of less than a hundred femtoseconds in the late 1980s enabled scientists to initiate and observe the evolution of chemical reactions. This powerful approach combined the interactions of light and matter and unleashed an unprecedented metrology concept that tracks the interactions of atoms and molecules in their natural timescales. Electron wavepacket dynamics take place in the attosecond range, a thousand times faster than molecules. In optical terms, such durations typically last less than the half-cycle duration of optical fields. Consequently, the investigation of such electronic processes necessitates measurement techniques capable of resolving the oscillations of the electric field of light. The primary objective of this thesis is to develop and advance novel field characterisation techniques based on photoconductive sampling. The first portion of this thesis addresses broadband field characterisation based on nonlinear photoconductive sampling. A theoretical analysis of current formation and localisation in solids is presented, prompting the fabrication of a heterostructured sample with the aim of enhancing the magnitude of the signal obtained from the measurement technique. A thorough proof-of-principle experiment is performed, whereby a significant enhancement in signal magnitude is established. As a consequence of signal improvement, the heterostructured sample reaches the desired stability regime earlier than its traditional bulk counterparts. Moreover, the performance of the heterostructured sample for field characterisation is compared to fused silica and benchmarked against the well-established technique of electro-optic sampling. These results pave the way towards field sampling in low pulse energy systems. The following section details broadband field characterisation based on linear photoconductive sampling by employing tailored pulses from a waveform synthe- siser. Visible-ultraviolet pulses are utilised to inject carriers in a common semi- conductive material (gallium phosphide), enabling the complete characterisation of a mid-infrared test field. Furthermore, the technique is validated against electro-optic sampling. When compared to electro-optic sampling, the response function of linear photoconductive sampling is concerned with the intensity envelope of the gating field, relaxing the strict requisites on the temporal phase of the gate. The demonstrated results represent a significant achievement in extending field sampling techniques beyond 100 THz and towards the visible range. Finally, a machine learning-based algorithm for denoising waveforms obtained from a laboratory setting is developed and implemented. The algorithm is based on a one-dimensional convolutional neural network, ideal for processing data presented on an evenly spaced grid. The model is compared with well-established methodologies, namely denoising via the fast Fourier transform and wavelet analysis and exhibits excellent performance, extending the repertoire of tools typically used for combating noise. The field characterisation methodologies presented in this thesis pave the way towards accessible and cost-effective field sampling techniques, enabling researchers to study field-induced electron dynamics in matter and usher in ultrafast optoelectronic signal processing towards the PHz range. In general, the field characterisation techniques presented occupy a small footprint, and the measurements take place in ambient air conditions, facilitating their integration in existing experimental infrastructures. With the aid of AI-accelerator chips, the machine learning tool developed in this thesis can be implemented during laboratory measurements as a concurrent denoising technique

High-resolution broadband rotational spectroscopy and electrical discharge experiments of astrochemically relevant molecules

Since the discovery of molecules in the interstellar medium in the 1960s, the quest to fully characterise the chemical inventory of interstellar space has resulted in the detection of over 200 distinct molecules. This has been achieved through the combined efforts of laboratory spectroscopy and observational astronomy. Advances in the field of radio astronomy, in particular with the increased sensitivity, widened frequency bandwidth of operation, and higher angular resolution of facilities such as the Atacama Large Millimeter/submillimeter Array, is producing a high throughput of data of unprecedented quality. In order to analyse this data, and, in turn, to address questions surrounding molecular complexity and chemical evolution in space, there needs to be concurrent progress in the field of high-resolution laboratory spectroscopy. Rotational spectroscopy is a uniquely suited technique for providing data that enables searches for molecules in the interstellar medium. The experimentally recorded transition frequencies, or the line frequencies predicted from the rotational constants derived from spectral analysis, are used to identify molecular species in observational spectra. Rotational spectroscopy is a high-resolution, highly sensitive technique from which structural data about the probed molecules can be obtained. In fact, the fingerprint nature of the technique facilitates the unambiguous conformer- and isotopologue-specific laboratory assignment and interstellar observation of studied molecules. The spectrometers used throughout this work are the Hamburg COMPACT Spectrometer (2-18 GHz), the 18-26 GHz Spectrometer, and a W-band Spectrometer (75-110 GHz) from BrightSpec, Inc. The operating ranges overlap with a number of observational facilities, putting the data presented here at the forefront of experimental astrochemistry and radio astronomy. The necessary laboratory data to perform observational searches for a number of nitrogen- and oxygen-containing astrochemically relevant molecules is delivered in this thesis. The pure rotational spectra of the vibronic ground state of iso-propyl cyanide, the six lowest energy conformers of 1,2-propanediol, two, four, three, and seven ground state conformers of alaninol, valinol, leucinol, and isoleucinol, respectively, and the ground state of imidazole were assigned. The resulting line lists and rotational constants are the most precise descriptions of these molecules available to date, and they can be used for comparison to observational spectra. Further to this, because of the assignment of isotopologues in natural abundance, extensive structural information is obtained for the molecules studied. The room-temperature experiments performed on the W-band spectrometer allowed for the assignment of low-lying vibrationally excited states, which, if detected in the interstellar medium, can act as probes of the region’s physical conditions. The laboratory data has been used to search for some of the studied species to-wards the giant molecular cloud Sagittarius B2. Searches for the vibrational states of iso-propyl cyanide in the Re-exploring Molecular Complexity with ALMAline survey of Sagittarius B2(N2b) revealed the presence of the four lowest energy states ν30, ν29, ν17, and ν16. The detected line profiles could be accurately described using local thermodynamic conditions at 150 K. Imidazole was searched for in the Exploring Molecular Complexity with ALMA observational data set towards Sagittarius B2(N), and the ring structure was not detected towards the region. A search towards the Taurus Molecular Cloud, where the aromatic molecule benzonitrile was previously detected, is suggested. Further, an electrical discharge nozzle was implemented and optimised on theW-band spectrometer. Performing electrical discharge experiments will not only permit the characterisation of reactive species and new molecules, but also allow for the consideration of formation pathways and mechanisms to these molecules from the precursors used. The discharge of acetaldehyde was shown to produce the formyl radical, ketene, propyne, acrolein, and acetone. Mapping the distributions of these species in molecular clouds, something which is possible thanks to the high spatial resolution of observational data sets, can ascertain whether these laboratory determined reaction pathways are relevant for interstellar chemistry. Experimental modifications to promote the detection of products that incorporate functional groups from multiple precursors is also discussed. The data presented in this thesis will enable searches for the studied molecules in the interstellar medium, and in the case of the amino alcohols, this could establish a new class of interstellar molecule. Detections of these molecules will increase the knowledge of the complexity of interstellar space. The simultaneous mapping of the spatial distributions of molecules and their potential precursors, which can be guided by the results of electrical discharge experiments, will contribute to the understanding of the chemistry occurring in these extraterrestrial environments.Seit der Entdeckung der ersten Moleküle im interstellaren Raum in den 1960er Jahren hat das Bestreben, das chemische Inventar des interstellaren Raums vollständig zu charakterisieren, zum Nachweis von über 200 verschiedenen Molekülen geführt. Dies wurde durch die kombinierten Anstrengungen von Laborspektroskopie und Teleskopbeobachtungen erreicht. Fortschritte auf dem Gebiet der Radioastronomie, insbesondere mit der erhöhten Empfindlichkeit, der erweiterten Frequenzbandbreite und der höheren Winkelauflösung von Einrichtungen wie dem Atacama Large Millimeter/Submillimeter Array, führen zu einem hohen Datendurchsatz von beispielloser Qualität. Um diese Daten zu analysieren und damit Fragen der molekularen Komplexität und der chemischen Entwicklung im Weltraum zu beantworten, sind gleichzeitig Fortschritte auf dem Gebiet der hochauflösenden Laborspektroskopie erforderlich. Die Rotationsspektroskopie eignet sich hervorragend zur Bereitstellung von Daten, die die Suche nach Molekülen im interstellaren Raum ermöglichen. Die experimentell gewonnenen Übergangsfrequenzen oder die Linienfrequenzen, die aus den experimentell bestimmten Rotationskonstanten vorhergesagt werden, werden zur Identifizierung von Molekülspezies in Spektren aus radioastronomischen Beobachtungen verwendet. Die Rotationsspektroskopie ist eine hochauflösende, hochempfindliche Technik, mit der auch Strukturdaten über die untersuchten Moleküle gewonnen werden können. Tatsächlich erleichtert diese fingerabdruckartige Technologie die eindeutige konformeren- und isotopologenspezifische Identifikation im Labor und nachfolgend die interstellare Beobachtung der untersuchten Moleküle. Die in dieser Arbeit verwendeten Spektrometer sind das Hamburger COMPACT-Spektrometer (2-18 GHz), das 18-26 GHz-Spektrometer und ein W-Band-Spektrometer (75-110 GHz) von BrightSpec, Inc. Die abgedeckten Frequenzbereiche der Spektrometer überlappen mit einer Reihe von Radioteleskopen, so dass die hier vorgestellten Daten für eine Weiterentwicklung der Astrochemie und Radioastronomie von großer Relevanz sind. In dieser Arbeit werden die erforderlichen Labordaten für eine erfolgreiche Suche nach einer Reihe von stickstoff- und sauerstoffhaltigen, astrochemisch relevanten Molekülen geliefert. Es wurden die reinen Rotationsspektren des vibronischen Grundzustandes von iso-Propylcyanid, die sechs niederenergetischen Konformere von 1,2-Propandiol, zwei, vier, drei und sieben Grundzustandskonformere von Alaninol, Valinol, Leucinol bzw. Isoleucinol und der Grundzustand von Imidazol zugeordnet. Die daraus resultierenden Linienlisten und Rotationskonstanten sind die präzisesten Beschreibungen dieser Moleküle, die bisher verfügbar sind, und sie können zum Vergleich mit radioastronomischen Spektren verwendet werden. Darüber hinaus erhält man durch die Zuordnung von Isotopologen in natürlicher Häufigkeit umfangreiche Strukturinformationen für die untersuchten Moleküle. Die mit dem W-Band-Spektrometer durchgeführten Raumtemperaturexperimente erlaubten die Zuordnung tiefliegender schwingungsangeregter Zustände, die, wenn sie im interstellaren Raum detektiert werden, als Sonden für die physikalischen Bedingungen der Region dienen können. Die Labordaten wurden zur Suche nach einigen der untersuchten Moleküle in Richtung der riesigen Molekülwolke Sagittarius B2 verwendet. Die Suche nach den Schwingungszuständen voniso-Propylcyanid in der ”Re-exploring Molecular Complexity with ALMA”-Suche von Sagittarius B2(N2b) ergab das Vorhandensein der vier niedrigsten Schwingungszustände ν30, ν29, ν17, und ν16. Die entdeckten Linienprofile konnten mit Hilfe der lokalen thermodynamischen Bedingungen bei 150K genau beschrieben werden. Nach Imidazol wurde im ”Exploring Molecular Complexity with ALMA”-Beobachtungsdatensatz in Richtung Sagittarius B2(N) gesucht, allerdings konnte diese Ringstruktur bisher nicht nachgewiesen werden. Eine Suche in Richtung der Taurus-Molekülwolke, wo zuvor das aromatische Molekül Benzonitril nachgewiesen wurde, wird vorgeschlagen. Weiterhin wurde eine elektrische Entladungsdüse implementiert und am W-Band-Spektrometer optimiert. Die Durchführung elektrischer Entladungsexperimente wird nicht nur die Charakterisierung reaktiver Spezies und neuer Moleküle, sondern auch die Analyse von Bildungswegen und -mechanismen dieser Moleküle aus den verwendeten Vorläufermolekülen ermöglichen. Es konnte gezeigt werden, dass bei der Entladung von Acetaldehyd das Formylradikal, Keten, Propin, Acrolein und Aceton entstehen. Durch die Kartierung der Verteilungen dieser Spezies in Molekülwolken, die dank der hohen räumlichen Auflösung der Beobachtungsdatensätze heutzutage möglich ist, kann im Prinzip festgestellt werden, ob diese im Labor ermittelten Reaktionswege für die interstellare Chemie relevant sind. Experimentelle Modifikationen für einen verbesserten Nachweis von Produkten, die funktionelle Gruppen aus mehreren Vorläufermolekülen enthalten, werden ebenfalls diskutiert. Die in dieser Arbeit vorgestellten Daten ermöglichen die Suche nach den untersuchten Molekülen im interstellaren Raum und könnten im Falle der Aminoalkohole eine neue Klasse interstellarer Moleküle etablieren. Der Nachweis dieser Moleküle wird das Wissen über die Komplexität des interstellaren Raums erweitern. Die gleichzeitige Kartierung der räumlichen Verteilung der Moleküle und ihrer potentiellen Vorläufer, die sich an den Ergebnissen von Experimenten mit elektrischen Entladungen orientieren kann, wird zum Verständnis der in diesen extraterrestrischen Umgebungen auftretenden Chemie beitragen