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In this thesis, I report studies investigating the neurobiology of conduct disorder (CD) – a disorder diagnosed in children and adolescents who display a persistent pattern of disruptive and aggressive behaviour. My particular focus is on the role of frontal, limbic and hypothalamic-pituitary-adrenal (HPA) axis systems, and especially whether CD-related alterations in these systems differ between males and females. A range of different imaging techniques were applied to data from the Neurobiological and Treatment of Adolescent Female Conduct Disorder study (Fem-NAT-CD). In study 1 (Chapter 4), we employed surface-based morphometry techniques to assess frontal and limbic (cortical and subcortical) brain structures. Similar patterns of CD-related related reductions in cortical volume, thickness, and surface area in the superior frontal gyrus were seen in both sexes. The second study (Chapter 5) assessed the shape of subcortical limbic structures. Youths with CD exhibited shape deformations (i.e., inward) in the shell of the nucleus accumbens compared to controls, independent of sex. The third study (Chapter 6) used spherical deconvolution basedtractography and virtually dissected key fronto-limbic white matter tracts, namely: the uncinate fasciculus, fornix, and the subgenual, retrosplenial and parahippocampal bundles of the cingulum. We observed reduced fractional anisotropy in the retrosplenial cingulum in the CD group relative to healthy controls. However, this result was moderated by sex: males with CD showed reduced, while females with CD showed increased fractional anisotropy compared to sex-matched healthy controls. Finally, we investigated sex differences in HPA axis function (Chapter 7) by measuring cortisol response during the Trier Social Stress Test for Children. Both males and females with CD showed blunted cortisol response to stress, and such effects were not explained by low levels of self-rated fear or anxiety. In a small, proof of concept analysis we observed a positive correlation between cortical volume of the superior frontal gyrus and cortisol reactivity. I conclude that the neurobiological basis of CD is relatively similar in males and females. Thus, previous findings in males with CD may also apply for females with CD. Suggestions for future research are presented and clinical implications are discussed.

This dissertation is focused on the design, development, and implementation of two high performance optical microscopy systems that enable study of neuronal circuit function in new and innovative ways.Firstly, an easily adopted, open-source miniature 2-photon microscope (UCLA 2P Miniscope) capable of recording calcium dynamics from neurons located in deep structures and in dendrites over a (445µm x 380µm) field of view (FOV) during free behavior is described. The system weighs approximately 4g and utilizes two on-board silicon-based photon detectors for highly sensitive measurements. All hardware is designed for high performance and ease of assembly, while minimizing cost. To test the 2P miniature microscope, recordings in three experimental conditions were conducted to highlight system capabilities during free behavior in mice. First, calcium dynamics from place cells in hippocampal area CA1 were recorded. Next, calcium transients from dendrites in retrosplenial cortex were resolved during 30 minutes of free behavior. Lastly, dentate granule cell activity was recorded at a depth of over 620µm, through an intact hippocampal formation during an open field behavior. The dentate granule cell recordings, to our knowledge, are the first optical recordings from these neurons ever performed in the intact hippocampus during free behavior. The miniature microscope itself and all supporting equipment are open-source and all files needed for building the scope can be accessed through the UCLA Golshani Lab GitHub repository. Secondly, a high-speed, open-source voltage imaging microscope is presented, capable of resolving (920µm x 460µm) fields of view at 500 frames per second. This microscope enables the study of fast-spiking neural populations such as interneurons with single action potential sensitivity over periods greater than 10 minutes. The system is also able to resolve activity from populations of many neurons simultaneously, with some recordings exceeding 30 active neurons in a single FOV. Additionally, this microscope system is able to quantify sub-threshold membrane potentials, making the recording of oscillatory dynamics and excitatory post synaptic potentials possible in large neural circuits in-vivo. Altogether, this high-speed, large FOV system enables new studies into the critical mechanisms key subpopulations of neurons employ to support computation and learning over time.Both of the microscope systems described here enable new insights into the function of the central nervous system. The first (Part I) is a miniature multiphoton microscope capable of studying fine structures deep in the brain during free and naturalistic behavior. The second (Part II) is a high-speed system able to record rapidly changing electrical dynamics across large neural populations. Together they will lead to new understandings of how the brain functions both in disease and health.

Sheet Illumination microscopy is a well developed tool in the bio-imaging community due to many inherent advantages. Increased photonic efficiency allows for lower power light sources to be used, which in turn reduce phototoxic damage at the sample over time. High fidelity, high SNR data can be collected from these systems due to their optical sectioning capabilities, and as such, many have been designed to operate within a limited parameter space. These instruments often follow traditional design logic, for specialization in one imaging condition, to observe only a single type of scientific data. This mentality yields high resolution results for a particular class of data, yet is limited in terms of flexibility. Here, the design and development of a user-configurable light sheet microscope is discussed, which uses a spatial phase modulator to dynamically shape and optimize the incident light sheet to perform highly in a number of temporal and spatial scales. The result is a general purpose microscopy platform for the observation of many biological phenomena.

Abstract. We study theoretically the stability of two superposed fluid layers heated laterally. The fluids are supposed to be immiscible, the interface undeformable and of infinite horizontal extension. Combined thermocapillary and buoyancy forces give rise to a basic flow when a temperature difference is applied. The calculations are performed for a melt of GaAs under a layer of molten B2O3, a configuration of considerable technological importance. Four different flow patterns and five temperature configurations are found for the basic state in this system. A linear stability analysis shows that the basic state may be destabilized by oscillatory motions leading to the so-called hydrothermal waves. Depending on the relative height of the two layers these hydrothermalwaves propagate parallel or perpendicular to the temperature gradient. This analysis reveals that these perturbations can alter significantly the liquid flow in the liquid-encapsulated crystal growth techniques.

This work is devoted to the theoretical study of the stability of two superposed horizontal liquid layers bounded by two solid planes and subjected to a horizontal temperature gradient. The liquids are supposed to immiscible with a nondeformable interface. The forces acting on the system are buoyancy and interfacial tension. Four different flow patterns and temperature profiles are found for the basic state. A linear perturbative analysis with respect to two- and three-dimensional perturbations reveals the existence of three kinds patterns. Depending on the relative height of both liquids several situations are predicted: either wave propagation from cold to the hot regions, or waves propagating in the opposite direction or still stationary longitudinal rolls. The behavior of three different pairs of liquids which have been used in experiments on bilayers under vertical gradient by other authors have been examined. The instability mechanisms are discussed and qualitative interpretation of the different behaviors exhibited by the system is provided. In some configurations it is possible to find a codimension-two point created by the interaction of two Hopf modes with different frequencies and wave numbers. These results suggest to consider two liquid layers as an interesting prototype for the study of propagation and interaction of waves in the context of the Be´nard-Marangoni problem.