Dissecting neural circuits for vision in nonhuman primates using fMRI-guided electrophysiology and optogenetics

The visual system is a remarkable platform that evolved to solve difficult computational problems such as detection, recognition, and classification of objects. Of great interest is the face-processing network, a sub-system buried deep in the temporal lobe, dedicated for analyzing specific type of objects (faces). In this thesis, I focus on the problem of face detection by the face-processing network. Insights obtained from years of developing computer-vision algorithms to solve this task have suggested that it may be efficiently and effectively solved by detection and integration of local contrast features. Does the brain use a similar strategy? To answer this question, I embark on a journey that takes me through the development and optimization of dedicated tools for targeting and perturbing deep brain structures. Data collected using MR-guided electrophysiology in early face-processing regions was found to have strong selectivity for contrast features, similar to ones used by artificial systems. While individual cells were tuned for only a small subset of features, the population as a whole encoded the full spectrum of features that are predictive to the presence of a face in an image. Together with additional evidence, my results suggest a possible computational mechanism for face detection in early face processing regions. To move from correlation to causation, I focus on adopting an emergent technology for perturbing brain activity using light: optogenetics. While this technique has the potential to overcome problems associated with the de-facto way of brain stimulation (electrical microstimulation), many open questions remain about its applicability and effectiveness for perturbing the non-human primate (NHP) brain. In a set of experiments, I use viral vectors to deliver genetically encoded optogenetic constructs to the frontal eye field and faceselective regions in NHP and examine their effects side-by-side with electrical microstimulation to assess their effectiveness in perturbing neural activity as well as behavior. Results suggest that cells are robustly and strongly modulated upon light delivery and that such perturbation can modulate and even initiate motor behavior, thus, paving the way for future explorations that may apply these tools to study connectivity and information flow in the face processing network.

Parasitic lasing suppression in high gain femtosecond petawatt Ti: sapphire amplifier

New parasitic lasing suppression techniques are developed and high gain amplification is demonstrated in a petawatt level Ti:sapphire amplifier based on the chirped pulse amplification (CPA) scheme. Cladding the large aperture Ti: sapphire with refractive-index matched liquid doped with absorber suppresses the transverse lasing. The acousto-optic programmable dispersive filter (AOPDF) is used to realize side-lobe suppression in the temporal profile of the compressed pulse. The 800 nm laser output with peak power of 0.89 PW and pulse width of 29.0 fs is demonstrated. (c) 2007 Optical Society of America.

Fluorescence microscopy of nicotinic acetylcholine receptors

Neuronal nicotinic acetylcholine receptors (nAChRs) are pentameric ligand gated ion channels abundantly expressed in the central nervous system. Changes in the assembly and trafficking of nAChRs are pertinent to disease states including nicotine dependence, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), and Parkinson’s disease (PD). Here we investigate the application of high resolution fluorescence techniques for the study of nAChR assembly and trafficking. We also describe the construction and validation of a fluorescent α5 subunit and subsequent experiments to elucidate the cellular mechanisms through which α5 subunits are expressed, assembled into mature receptors, and trafficked to the cell surface. The effects of a known single nucleotide polymorphism (D398N) in the intracellular loop of α5 are also examined.

Additionally, this report describes the development of a combined total internal reflection fluorescence (TIRF) and lifetime imaging (FLIM) technique and the first application of this methodology for elucidation of stochiometric composition of nAChRs. Many distinct subunit combinations can form functional receptors. Receptor composition and stoichiometry confers unique biophysical and pharmacological properties to each receptor sub-type. Understanding the nature of assembly and expression of each receptor subtype yields important information about the molecular processes that may underlie the mechanisms through which nAChR contribute to disease and addiction states.

椭圆芯双模光纤干涉模斑中心间距的研究

通过弱波导近似的方法，讨论了椭圆芯双模光纤中沿光纤长轴的基模模斑半径Wx和短轴的基模模斑半径Wy尺寸，分析了它们的比值随入射光波长λ及纤芯半长轴与半短轴的比值a/b的变化规律。 针对基模LP01和第一高阶模LP11间的相位差变化，计算了双模干涉模斑的分布结构。计算结果表明，当基模LP01和第一高阶模LP11间的相位差为π/2时，两瓣干涉模斑有相同的结构特征。同时，两瓣模斑的中心间距S随Wx/Wy的的增加而变大。而且，当入射波长在0.65 μm和 1.31 μm之间变化时，结合两瓣模斑的中心间距S随Wx/Wy的变化规律，首次给出了S的计算公式。这对于实际应用如传感器和光纤耦合器件设计是很重要的。

Neural Prosthetics and Parietal Cortex

In the last decade, research efforts into directly interfacing with the neurons of individuals with motor deficits have increased. The goal of such research is clear: Enable individuals affected by paralysis or amputation to regain control of their environments by manipulating external devices with thought alone. Though the motor cortices are the usual brain areas upon which neural prosthetics depend, research into the parietal lobe and its subregions, primarily in non-human primates, has uncovered alternative areas that could also benefit neural interfaces. Similar to the motor cortical areas, parietal regions can supply information about the trajectories of movements. In addition, the parietal lobe also contains cognitive signals like movement goals and intentions. But, these areas are also known to be tuned to saccadic eye movements, which could interfere with the function of a prosthetic designed to capture motor intentions only. In this thesis, we develop and examine the functionality of a neural prosthetic with a non-human primate model using the superior parietal lobe to examine the effectiveness of such an interface and the effects of unconstrained eye movements in a task that more closely simulates clinical applications. Additionally, we examine methods for improving usability of such interfaces.

The parietal cortex is also believed to contain neural signals relating to monitoring of the state of the limbs through visual and somatosensory feedback. In one of the world’s first clinical neural prosthetics based on the human parietal lobe, we examine the extent to which feedback regarding the state of a movement effector alters parietal neural signals and what the implications are for motor neural prosthetics and how this informs our understanding of this area of the human brain.

Toward Understanding Astrophysical Phenomena

Fast radio bursts (FRBs), a novel type of radio pulse, whose physics is not yet understood at all. Only a handful of FRBs had been detected when we started this project. Taking account of the scant observations, we put physical constraints on FRBs. We excluded proposals of a galactic origin for their extraordinarily high dispersion measures (DM), in particular stellar coronas and HII regions. Therefore our work supports an extragalactic origin for FRBs. We show that the resolved scattering tail of FRB 110220 is unlikely to be due to propagation through the intergalactic plasma. Instead the scattering is probably caused by the interstellar medium in the FRB's host galaxy, and indicates that this burst sits in the central region of that galaxy. Pulse durations of order $\ms$ constrain source sizes of FRBs implying enormous brightness temperatures and thus coherent emission. Electric fields near FRBs at cosmological distances would be so strong that they could accelerate free electrons from rest to relativistic energies in a single wave period. When we worked on FRBs, it was unclear whether they were genuine astronomical signals as distinct from `perytons', clearly terrestrial radio bursts, sharing some common properties with FRBs. Recently, in April 2015, astronomers discovered that perytons were emitted by microwave ovens. Radio chirps similar to FRBs were emitted when their doors opened while they were still heating. Evidence for the astronomical nature of FRBs has strengthened since our paper was published. Some bursts have been found to show linear and circular polarizations and Faraday rotation of the linear polarization has also been detected. I hope to resume working on FRBs in the near future. But after we completed our FRB paper, I decided to pause this project because of the lack of observational constraints.

The pulsar triple system, J0733+1715, has its orbital parameters fitted to high accuracy owing to the precise timing of the central $\ms$ pulsar. The two orbits are highly hierarchical, namely $P_{\mathrm{orb,1}}\ll P_{\mathrm{orb,2}}$, where 1 and 2 label the inner and outer white dwarf (WD) companions respectively. Moreover, their orbital planes almost coincide, providing a unique opportunity to study secular interaction associated purely with eccentricity beyond the solar system. Secular interaction only involves effect averaged over many orbits. Thus each companion can be represented by an elliptical wire with its mass distributed inversely proportional to its local orbital speed. Generally there exists a mutual torque, which vanishes only when their apsidal lines are parallel or anti-parallel. To maintain either mode, the eccentricity ratio, $e_1/e_2$, must be of the proper value, so that both apsidal lines precess together. For J0733+1715, $e_1\ll e_2$ for the parallel mode, while $e_1\gg e_2$ for the anti-parallel one. We show that the former precesses $\sim 10$ times slower than the latter. Currently the system is dominated by the parallel mode. Although only a little anti-parallel mode survives, both eccentricities especially $e_1$ oscillate on $\sim 10^3\yr$ timescale. Detectable changes would occur within $\sim 1\yr$. We demonstrate that the anti-parallel mode gets damped $\sim 10^4$ times faster than its parallel brother by any dissipative process diminishing $e_1$. If it is the tidal damping in the inner WD, we proceed to estimate its tidal quantity parameter ($Q$) to be $\sim 10^6$, which was poorly constrained by observations. However, tidal damping may also happen during the preceding low-mass X-ray binary (LMXB) phase or hydrogen thermal nuclear flashes. But, in both cases, the inner companion fills its Roche lobe and probably suffers mass/angular momentum loss, which might cause $e_1$ to grow rather than decay.

Several pairs of solar system satellites occupy mean motion resonances (MMRs). We divide these into two groups according to their proximity to exact resonance. Proximity is measured by the existence of a separatrix in phase space. MMRs between Io-Europa, Europa-Ganymede and Enceladus-Dione are too distant from exact resonance for a separatrix to appear. A separatrix is present only in the phase spaces of the Mimas-Tethys and Titan-Hyperion MMRs and their resonant arguments are the only ones to exhibit substantial librations. When a separatrix is present, tidal damping of eccentricity or inclination excites overstable librations that can lead to passage through resonance on the damping timescale. However, after investigation, we conclude that the librations in the Mimas-Tethys and Titan-Hyperion MMRs are fossils and do not result from overstability.

Rubble piles are common in the solar system. Monolithic elements touch their neighbors in small localized areas. Voids occupy a significant fraction of the volume. In a fluid-free environment, heat cannot conduct through voids; only radiation can transfer energy across them. We model the effective thermal conductivity of a rubble pile and show that it is proportional the square root of the pressure, $P$, for $P\leq \epsy^3\mu$ where $\epsy$ is the material's yield strain and $\mu$ its shear modulus. Our model provides an excellent fit to the depth dependence of the thermal conductivity in the top $140\,\mathrm{cm}$ of the lunar regolith. It also offers an explanation for the low thermal inertias of rocky asteroids and icy satellites. Lastly, we discuss how rubble piles slow down the cooling of small bodies such as asteroids.

Electromagnetic (EM) follow-up observations of gravitational wave (GW) events will help shed light on the nature of the sources, and more can be learned if the EM follow-ups can start as soon as the GW event becomes observable. In this paper, we propose a computationally efficient time-domain algorithm capable of detecting gravitational waves (GWs) from coalescing binaries of compact objects with nearly zero time delay. In case when the signal is strong enough, our algorithm also has the flexibility to trigger EM observation {\it before} the merger. The key to the efficiency of our algorithm arises from the use of chains of so-called Infinite Impulse Response (IIR) filters, which filter time-series data recursively. Computational cost is further reduced by a template interpolation technique that requires filtering to be done only for a much coarser template bank than otherwise required to sufficiently recover optimal signal-to-noise ratio. Towards future detectors with sensitivity extending to lower frequencies, our algorithm's computational cost is shown to increase rather insignificantly compared to the conventional time-domain correlation method. Moreover, at latencies of less than hundreds to thousands of seconds, this method is expected to be computationally more efficient than the straightforward frequency-domain method.

Lau cavity and phase locking of laser arrays

The Lau cavity is the self-imaging cavity with a phase corrector under the Lau reimaging condition. The author proposes the use of the Lau cavity to utilize both the Talbot and the Lau effects for phase locking one-dimensional and two-dimensional diode-laser arrays into a single-lobe coherent beam. Analyses on the self-reproducing of a coherent lasing field and the reimaging of initial incoherent radiation are given.

A computer-aided investigation of motion detection units in the fly

This work deals with two related areas: processing of visual information in the central nervous system, and the application of computer systems to research in neurophysiology.

Certain classes of interneurons in the brain and optic lobes of the blowfly Calliphora phaenicia were previously shown to be sensitive to the direction of motion of visual stimuli. These units were identified by visual field, preferred direction of motion, and anatomical location from which recorded. The present work is addressed to the questions: (1) is there interaction between pairs of these units, and (2) if such relationships can be found, what is their nature. To answer these questions, it is essential to record from two or more units simultaneously, and to use more than a single recording electrode if recording points are to be chosen independently. Accordingly, such techniques were developed and are described.

One must also have practical, convenient means for analyzing the large volumes of data so obtained. It is shown that use of an appropriately designed computer system is a profitable approach to this problem. Both hardware and software requirements for a suitable system are discussed and an approach to computer-aided data analysis developed. A description is given of members of a collection of application programs developed for analysis of neuro-physiological data and operated in the environment of and with support from an appropriate computer system. In particular, techniques developed for classification of multiple units recorded on the same electrode are illustrated as are methods for convenient graphical manipulation of data via a computer-driven display.

By means of multiple electrode techniques and the computer-aided data acquisition and analysis system, the path followed by one of the motion detection units was traced from open optic lobe through the brain and into the opposite lobe. It is further shown that this unit and its mirror image in the opposite lobe have a mutually inhibitory relationship. This relationship is investigated. The existence of interaction between other pairs of units is also shown. For pairs of units responding to motion in the same direction, the relationship is of an excitatory nature; for those responding to motion in opposed directions, it is inhibitory.

Experience gained from use of the computer system is discussed and a critical review of the current system is given. The most useful features of the system were found to be the fast response, the ability to go from one analysis technique to another rapidly and conveniently, and the interactive nature of the display system. The shortcomings of the system were problems in real-time use and the programming barrier—the fact that building new analysis techniques requires a high degree of programming knowledge and skill. It is concluded that computer system of the kind discussed will play an increasingly important role in studies of the central nervous system.

Tunable transverse superresolution with phase-only pupil filters

A new set of pure phase filters for realizing transverse superresolution is presented in this paper. The filters, whose significant features are their ability to tune and their simplicity, consist of one half-wave plate between two quarter-wave plates; the half-wave plate is made of two zones that can rotate with respect to each other. By rotating any zone of the half-wave plate, the central lobe width of the irradiance point spread function (PSF) in the transverse direction can be tunably reduced. At the same time, the axial intensity distribution is analysed in detail.

Smoothing the side lobes of a focused pattern by spectral dispersion in the broadband laser

Starting from the Huygens-Fresnel diffraction integral, the propagation equations of a broadband laser passing through a dispersive lens and a dispersive wedge are derived. Smoothing effect on the side lobes of the focused pattern is achieved as the broadband laser passes through the lens because of the spectral dispersion of the lens. By inserting a dispersive wedge behind the lens, better smoothing effect is realized because a relative position shift between focused patterns of different frequency components is generated due to the spectral dispersion of the wedge. Smoothing effect on the side lobe is obtained even with small bandwidth of the broadband laser as the wedge is used. (c) 2006 Elsevier GmbH. All rights reserved.

Dimorfismo sexual e polimorfismo no gênero Ptychoderes Schoenherr, 1823 (Coleoptera Anthribidae, Anthribinae, Ptychoderini)

O dimorfismo sexual exibido por machos polifênicos em algumas espécies do gênero Ptychoderes envolve variação no rostro, antena e ventritos. A existência de polifenismo pode ser um importante componente no processo evolutivo por meio de novidades morfológicas e comportamentais. O objetivo desse estudo foi determinar a variação em caracteres morfométricos, polifenismo em machos, variação de estruturas com conhecido dimorfismo sexual, possíveis padrões alométricos e testar estas inferências para Ptychoderes através do mapeamento do dimorfismo sexual e de machos em uma reconstrução filogenética de Ptychoderes usando Mesquite 2.04. Foram medidas 23 variáveis morfométricas em 510 espécimes com as seguintes análises realizadas: análises de cluster, analises de componentes principais (PCA), analise de variáveis canônicas (AVC), análise de regressão por eixo maior reduzido (RMA). Cada tipo de dimorfismo foi mapeado em uma filogenia prévia como dois estados separados usando parcimônia. Para todas as espécies o dimorfismo sexual apresentou diferenças significativas entre os sexos com relação aos segmentos antenais (II- X).O compriemtno do rosto e ventrito V foram confirmados como indicativos de dimorfismo sexual (exceto em P. jordani). A única espécie em que não ocorreu machos polifenicos foi P. depressus. Nas outras espécies machos grandes e pequenos diferem significantemente para muitas variáveis com similaridades e diferenças. Na ACP, o primeiro componente (PC1) apresentou alta porcentagem de variância nos dados de todas as espécies; apresentou loadings de mesmo sinal sugerindo diferenças relacionadas ao tamanho para as espécies P. jordani, P. depressus, P. virgatus, P. mixtus e P. callosus e para as espécies P. viridanus, P. antiquus, P. elongates e P. nebulosus apresentou loadings positivos e negativos sugerindo diferenças relacionadas a forma (alometria). O PC2 apresentou loadings positivos e negativos para todas as espécies, um provável componente alométricos. A AVC confirmou os grupos: machos grandes, machos pequenos e fêmeas quando estes ocorreram. Nós encontramos diferentes padrões alométricos para todas as espécies com diferenças e semelhanças entre as espécies. Todos esses resultados confirmam a hipótese de polifenismo em machos e dimorfismo sexual para Ptychhoderes. A análise dos padrões alométricos para o dimorfismo sexual revelou alometria positiva para o comprimento do rostro (CR1) em machos e fêmeas, com os ventritos apenas em machos. Padrões alométricos positivos relacionados ao polifenismo nos antenômeros foram confirmados para os machos grandes e pequenos de quase todas as espécies exceto em P. nebulosus. O ancestral de clados na filogenia de Ptychoderes foi inferido para machos polifênicos (exceto P. depressus) com variáveis no rostro, antenas e ventritos indicativas de dimorfismo sexual com alometria positiva. Estes padrões poderiam estar ligados com o comportamento de proteção das fêemeas realizados por machos grandes durante a oviposição.

Superresolution by three-zone pure phase plate with 0, pi, 0 phase variation

Superresolution is very important in imaging and optical storage systems, and has attracted much attention. In this article, concentric three-zone phase plate with 0, pi, 0 phase variation has been investigated numerically to show that this kind of phase plate can be used to obtain three-dimensional superresolution. In addition, the number of intensity maximum, focal depth, focal shift, full-width half-maximum, and relative intensity of side lobe are listed for different radii of the phase zones, which paves the way for design of the phase plate. Therefore, one can choose values of radii for desired intensity distribution in focal region, such as for the purpose of radial superresolution with high focal depth in optical storage. (c) 2006 Elsevier Ltd. All rights reserved.

Análise molecular e morfométrica da próstata ventral de ratos injetados com leptina

O objetivo deste estudo foi avaliar o efeito da administração de leptina no lobo ventral da próstata de ratos adultos. Vinte ratos Wistar machos e adultos foram divididos em 2 grupos: L - animais foram injetados com 50 μL diária de leptina (8 μg / 100 g PC, subcutânea) durante quatro dias e C - animais receberam o mesmo volume de solução salina. Perfil lipídico e níveis séricos de testosterona foram avaliados. O lobo ventral da próstata foi processado para análise histomorfométrica. Expressão dos genes da aromatase, receptor de andrógeno, receptores de estrógeno (α e β) e as isoformas dos receptores de leptina longa (Ob-Rb) e curta (Ob-Ra) foram avaliados por PCR em tempo real. Proliferação celular foi avaliada por imuno-histoquímica com PCNA. Os dados foram expressos como média  erro padrão e analisados pelo teste t de Student. Níveis séricos de colesterol aumentaram (C = 39,7 4,2; L = 55,2 4,2, mg / dL, P ≤ 0,02) e de testosterona (C = 1,6 0,43; L = 0,6 0,15, ng / dL, P ≤ 0,03) diminuíram no grupo L. A análise histomorfométrica mostrou uma redução na densidade de células (C = 8868 242; L = 8.211 210, mm2; P ≤ 0,04), na área total (C = 0,24 0,026; L = 0,10 0,009, mm2; P ≤ 0,001) e na área interna dos ácinos (C = 0,16 0,009; L = 0,08 0,006, mm2; P ≤ 0,0002). Por outro lado, houve um aumento na altura do epitélio (C = 17,3 0,3; L = 22,8 0,2 m, P ≤ 0,0001) e no número de ácinos (C = 7,0 0,2; L = 8,7 0,1, mm2; P ≤ 0,0002). As análises histomorfométrica juntamente com os resultados imuno-histoquímicos para PCNA sugerem que a leptina aumenta a proliferação celular. Em relação à expressão gênica, o tratamento de leptina aumentou a expressão de todos os genes, mas ER-α, em mais de 200 vezes em comparação com a expressão no grupo C. Em conclusão, neste trabalho mostramos que a leptina tem um efeito direto sobre a próstata de ratos adultos levando a um aumento na proliferação celular e na expressão gênica da aromatase, receptor de androgênio, nas isoformas dos receptores de leptina e receptores de estrogênios alfa e beta que são importantes para a fisiologia normal do tecido prostático

Comparison of uniform amplitude beam and intercepted Gaussian beam superresolution theories

The general superresolution theories for uniform amplitude beams and intercepted Gaussian beams are investigated. For these two types of incident beam, both two-zone amplitude and pure-phase filters are adopted to provide specific numerical descriptions of their differences in superresolution performances. Simulated results of comparisons between their performances indicate that, with the same spot size ratio, the intercepted Gaussian beam achieves a higher central image brightness ratio and significantly lower side-lobe effect irrespective of the filter used. (c) 2008 Elsevier Ltd. All rights reserved.

A novel hollow-core holey fibre with random hole distributions in the cladding

We provide a novel hollow-core holey fibre that owns a random distribution of air holes in the cladding. Our experiments demonstrate that many of the features previously attributed to photonic crystal fibres with perfect arrangement of air holes, in particular, photonic bandgap guidance, can also be obtained in the fibre. Additionally, this fibre exhibits a second guided mode with both the two-lobe patterns, and each pattern is in different colour.