Browsing by Subject "Neuroscience"

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The 8th annual computational and systems neuroscience (Cosyne) meeting
(Neural Systems and Circuits, 2011-04-20) Histed, Mark H.; Pillow, Jonathan W.
The 8th annual Computational and Systems Neuroscience meeting (Cosyne) was held February 24-27, 2011 in Salt Lake City, Utah (abstracts are freely available online: http://www.cosyne.org/c/index.php?title=Cosyne2011_Program webcite). Cosyne brings together experimental and theoretical approaches to systems neuroscience, with the goal of understanding neurons, neural assemblies, and the perceptual, cognitive and behavioral functions they mediate. The range of questions available to systems and computational neuroscience has grown substantially in recent years, with both theoretical and experimental approaches driven by the increasing availability of data about neural circuits and systems. The Cosyne meeting has reflected this growth, nearly doubling in size since the first meeting in 2004, to a new record of nearly 600 attendees this year. It remains single-track, which allows discussions of presentations to drive scientific interaction between attendees with diverse backgrounds. Poster sessions take place each evening, which provide a forum for intense scientific conversations that frequently spill out into more informal settings late at night. The meeting is followed by two days of workshops, held at the Snowbird ski resort, which feature more specialized talks and interactive discussions on a wide collection of topics, this year ranging from consciousness and compressed sensing to dynamics, learning, and perception.
Affecting violence : narratives of Los feminicidios and their ethical and political reception
(2012-12) Huerta Moreno, Lydia Cristina; Robbins, Jill, 1962-; Domínguez Ruvalcaba, Héctor, 1962-; Arroyo, Jossianna; Chapelle-Wojciehowski, Hannah; Ravelo-Blancas, Patricia; Pia Lara, Maria
In Mexico there is an increasing lack of engagement of the Mexican government and its citizens towards resolving violence. In the 20th century alone events such as the Revolution of 1910, La Guerra Cristera, La Guerra Sucia, and most recently Los Feminicidios and Calderon’s War on Drugs are representative of an ethos of violence withstood and inflicted by Mexicans towards women, men, youth, and marginalized groups. This dissertation examines Los Feminicidios in Ciudad Juarez and the cultural production surrounding them: chronicles, novels, documentaries and films. In it I draw on Aristotle’s influential Nicomachean Ethics, Victoria Camps’ El gobierno de las emociones (2011), María Pía Lara’s Narrating Evil (2007), Vittorio Gallese’s and other scientists’ research on neuroscience empathy and neurohumanism, and socio-political essays in order to theorize how a pathos-infused understanding of ethos might engage a reading and viewing public in what has become a discourse about violence determined by a sense of fatalism. Specifically, I argue that narrative and its interpretations play a significant role in people’s emotional engagement and subsequent cognitive processes. I stress the importance of creating an approach that considers both pathos and logos as a way of understanding this ethos of violence. I argue that by combining pathos and logos in the analysis of a cultural text, we can break through the theoretical impasse, which thus far has resulted in exceptionalisms and has been limited to categorizing as evil the social and political mechanisms that may cause this violence.
Camouflage detection & signal discrimination : theory, methods & experiments
(2022-05-05) Das, Abhranil; Geisler, Wilson S.; Reichl, L. E.; Florin, Ernst-Ludwig; Marder, Michael
Camouflage is an amazing feat of evolution, but also impressive is the ability of biological visual systems to detect them. They are the result of an evolutionary arms race that exposes many detection strategies and their limits. In this thesis, we investigate the principles of human detection of maximally-camouflaged objects, i.e. whose texture exactly mimics the background texture. Chapter 1 introduces and contextualizes the problem. In chapter 2, we develop a theory and model that extracts the relevant information in the image, and uses biologically plausible computations on them for detection. In chapter 3, we present a series of experiments which measured human camouflage detection ability along different dimensions of the task, such as across different textures and shapes. Chapter 5 is a reference on some methods and analysis used in the study. Chapter 6 describes mathematical methods and software on statistical signal discrimination that we developed to solve questions in visual detection, but with wider applications in other fields.
Circuit mechanisms of persistent activity in the primate cortex during working memory
(2019-05-13) Hart, Eric Lewis; Huk, Alexander C.; Hayhoe, Mary M; Mauk, Michael; Nauhaus, Ian M; Aldrich, Richard W
Working memory is the cognitive ability to actively maintain and manipulate information on the timescale of seconds. Neurons in the prefrontal and posterior parietal cortices of the primate brain remain active in absence of sensory input and appear to correlate with working memory. In this thesis, I investigate the mechanisms of persistent activity during working memory in the frontoparietal network of the macaque. By conducting simultaneous electrophysiological recordings in two of the key regions of this network, the lateral intraparietal area (LIP) and the frontal eye fields (FEF), and employing statistical models of the neural population activity, I characterized the interactions between neurons locally in each area and between these two distant brain regions. In a visuospatial working memory task, during which the subject must remember the spatial location of a target, I found strong recurrent activity on single trials both within and between these areas that was not due to the visual stimulus or the motor response. The strength and timescale of functional interactions between LIP and FEF were highly reciprocal and symmetrical, providing evidence for the theory that reverberatory activity in this circuit does, in fact, support working memory. However, contrary to current models of the frontoparietal network, area LIP exhibited greater local recurrent excitatory activity than FEF, and many individual neurons in LIP displayed activity on longer timescales. In addition, the concurrent population activity had a greater impact on the spiking activity of most neurons than each individual neuron’s own intrinsic drive, especially in LIP. This result further emphasizes the role of network mechanisms in generating and maintaining persistent activity. Taken together, these findings suggest revisions to the current models of working memory, and highlight the importance of studying population activity on single trials.
Considerations of the estrous cycle and female gonadal hormones in reward learning and memory
(2021-07-27) Hilz, Emily N.; Lee, Hongjoo Joanne; Monfils, Marie H; Gore, Andrea C; Morikawa, Hitoshi
Reward learning informs adaptive behaviors that allow us to advantageously engage with our environment; however, this learning can become maladaptive in some individuals and result in disordered behaviors like compulsive eating or drug-dependency. While the behavioral and neural substrates of reward learning are well established in males, much less attention has been given to these same systems in females. As females are at increased risk of disordered reward-seeking and female sex steroid hormones are potent modulators of the neural circuitry that underlies reward learning, developing a thorough understanding of how female hormonal states modulate this type of learning will help inform the development of individual-specific therapeutic interventions. In this dissertation, the findings of several studies using rat models of the estrous cycle in both food- and drug-learning are presented. Two aspects of reward learning are explored: renewal of extinguished conditioned food-seeking behavior, and conditioned place preference for amphetamine (AMP). Both paradigms provide novel methodologies for considering endogenous gonadal hormone states as a modulator of female conditioned responding and explore underlying neural mechanisms. Each experiment also considers conditioned orienting behavior as a potential indicator of individual differences in reward learning and memory. The experiments outlined here (1) consider the estrous cycle in the renewal of extinguished food-seeking, (2) examine estrous cycle modulation of immediate early gene Arc mRNA activity following exposure to separate learning contexts in the renewal paradigm, (3) consider conditioned orienting as a predictor of AMP place preference in female rats and, (4) modulate the estrous cycle with hormonal contraceptives to observe subsequent AMP place preference and related response measures. Behaviorally, a consistent result was found wherein the stage of the estrous cycle associated with high endogenous sex steroid hormone levels (i.e., proestrus or P) stimulated female conditioned responding (either increasing the likelihood of renewed food-seeking or contributing to increased drug preference and hedonic drug responsivity). Functionally, P modulated activity in the brain either in dopamine cells or in downstream targets such as the hippocampus and prefrontal cortex. These effects depended on the specific learning windows when cycle-stage was considered. From this research it is apparent that the hormonal state of the female learner contributes to behavioral outcomes.
Coordinated structural plasticity across synapses in the adult hippocampus
(2015-05) Chirillo, Michael August; Harris, Kristen M.; Bear, Mark F.; Colgin, Laura L.; Golding, Nace L.; Raab-Graham, Kimberly F.
Neural circuitry is determined primarily by trillions of synaptic junctions that link cells in the nervous system. Understanding how the structure of the synapse influences its function has been a central goal of cellular neuroscience since synapses were first recognized more than a century ago. Long-term potentiation (LTP), a long lasting enhancement of synaptic efficacy, is a well-characterized cellular correlate of learning and memory that results in dramatic structural remodeling of the synapse. Research has focused heavily on the postsynaptic structural remodeling that occurs to support LTP, but concomitant presynaptic and subcellular remodeling during LTP has been left largely unexplored. To address these questions, three-dimensional reconstructions from serial section electron microscopy of presynaptic boutons, vesicle pools, and dendritic smooth endoplasmic reticulum (SER) in hippocampal area CA1 were created and quantified. The data presented in this dissertation demonstrate that coordinated structural plasticity occurs at both pre- and postsynaptic sides of adult hippocampal synapses by 2 hours during LTP induced with theta burst stimulation. Presynaptically, the number of presynaptic boutons correlated perfectly with fewer dendritic spines during LTP that were previously reported, suggesting that synaptic units act as cohesive structures. Vesicle pools were mobilized and vesicle transport packets were moved into boutons or were released in transit. Dendritic SER is a ubiquitous intracellular membranous network involved in calcium signaling and protein modification. The complexity of SER influences the movement of diffusible membrane cargo. SER was dramatically remodeled during LTP, redistributing from the shaft of the dendrite into spines and becoming highly complex near synapses that were largest during LTP. As a preliminary investigation into how normal mechanisms of structural plasticity described in this dissertation might go awry under conditions of synaptic pathology, three-dimensional reconstructions of CA1 synaptic ultrastructure in a mouse model of Fragile X, which is known to express exaggerated mGluR-dependent long-term depression (LTD), were created and quantified. Synaptic ultrastructure was similar with that of the wild-type mouse, suggesting that structural malformation in FX might be confined to development or to other brain regions.
Effects of listening and brief practice on motor memory reconsolidation in musicians
(2024-08) Lader, Justin Harris; Simmons, Amy L., 1974-; Duke, Robert A; Scott, Laurie P; West, Justin; Jellison, Judith A; Hussain, Sara J
Musicians of all ages and skill levels engage in individual practice to improve the quality of repertoire performance as well as to increase their capacity to execute fundamental skills. As they work, new memories form and existing memories are updated so that skills continue to evolve over time. At the root of it all, changes in behavior are manifestations of changes in the brain. As new motor skills are acquired, the brain begins to encode neurological activity that underlies action in an early stage of memory formation. Memories for new skills are stabilized over time through covert process known as memory consolidation. During this process, stabilized motor memories are stored for later retrieval, and given enough time, memories may be enhanced so that subsequent performance exceeds what was achieved during practice. Recent research has also explored the neurological processes that update motor memories after they are initially consolidated. Recalling a motor skill reactivates the consolidated motor memory, by which the memory becomes labile. Subsequent reconsolidation processes update the motor memory and yield additional performance enhancement upon future recall. This dissertation presents two studies that are the first to explore motor memory reconsolidation in musicians, comparing brief with extended practice during reactivation, and testing the idea that motor memories might be reactivated using recorded auditory models. In the first study (chapter 2), I used a three-day protocol to compare the performances of participants in a control group with those assigned to one of three reactivation conditions: brief motor, extended motor, and auditory. Results indicated significant improvements in performance for participants in the brief and extended motor reactivation groups, and the two groups were not different from each other. Both of the motor reactivation groups performed significantly better than the control and auditory reactivation groups, which were not different from each other. In the second study (chapter 3), I used the same three-day protocol of the first study to explore the idea that auditory reactivation might be possible if learners heard a recorded model that matched their own level of individual performance at the end of training rather than the ideal recording of a professional pianist used in the first study. The performances of control and auditory reactivation groups were compared, and there were no differences between groups at test. Perhaps the most interesting finding of this work on reconsolidation in musicians is that brief practice yielded the same level of reconsolidation performance enhancement as extended practice. Although listening to an ideal or matched recorded model did not generate reconsolidation performance enhancement, these results in no way detract from the advantages offered to developing musicians who listen to models in classrooms, studios, and practice rooms. These studies will begin a line of research that will continue to explore the role of modeling in motor learning as well as to discover more about how musicians’ memories evolve over more extended periods of time as a result of practice, consolidation, and reconsolidation.
Embodied cognition, Latin pedagogy, and the rhetorical foundations of medieval vernacular poetry
(2015-05) Garbacz, Robert Scott; Woods, Marjorie Curry, 1947-; Birkholz, Daniel, 1967-; Wojciehowski, Hannah C; Johnson, Michael A; Walker, Jeffrey
This dissertation uses the insights of recent cognitive science to illuminate narrative and rhetorical strategies in the Eclogue of Theodolus, a Latin debate poem, and its French and English literary descendants. The Eclogue was wildly popular in classrooms throughout the Middle Ages and modeled for students ways to respond to stories with counter-stories, demonstrating rhetorical virtuosity by transforming images, words, and ideas. In doing so, it prepared the way for vernacular literary production. Chapters 1 and 2 focus on the ways the Eclogue’s narrative rhetoric, and particularly its imagery, was processedby medieval students using mental capacities recently revealed by modern cognitive linguistics and neuroscience. In the Eclogue, a character representing Christian truth triumphs over one representing pagan falsehood precisely through her ability to transform the cognitive and affective effects of the work’s visual and spatial rhetoric. Yet if the Eclogue emphasizes Christian superiority, the early French Roman d’Enéas deploys a similar specular rhetoric for a less respectable purpose. Lush descriptions of funeral monuments lure the reader away from what is otherwise the text’s central concern: legitimizing the French political order. These chapters show both the sophistication of medieval imagery and the discourses deployed to limit its power. Chapters 3 and 4 consider medieval theories of cognition. Chapter 3 focuses on the Owl and the Nightingale, a debate poem generally considered the first great work of Middle English literature. This poem undercuts the Eclogue’s lofty rhetoric by presenting myopic protagonists whose avian nature (in keeping with Neo-Aristotelian theory) is most clearly shown in their stubborn emphasis on their desires to live and kill. Similarly earthbound in its orientation is Chaucer’s House of Fame. This work, which begins with a survey of scholastic cognitive science and which offers a climactic ekphrasis in which the Eclogue takes a prominent place, offers both a deeply skeptical account of the ability of embodied humans to know the truth and a tour de force of medieval narrative rhetoric. Taken together, these discussions offer a survey of the power of medieval images on medieval brains and unearth a significant force in medieval intellectual culture.
The experience of absorption : comparison of the mental processes of meditation between emic yogic and etic neuroscientific perspectives on Ishvara Pranidhana meditation
(2010-05) Holte, Amy Jo 1972-; Neff, Kristin
Modernity has seen the exchange of ideas about cognition between western science and eastern meditation traditions. In particular, western ways of thinking about the natural world have infiltrated Indian theories of yoga. This intersection of ideas in the twentieth-century has resulted in a problematic trend to theorize yogic phenomena, including meditation, in scientific terms. These translations converge on explicating yogic processes within a context of advancing knowledge about the brain. This translational approach to bringing etic and emic perspectives together in the same framework results in interpretations of meditation that succumb to problems cognitive science faces at a broader level in theorizing cognition and mind-body interrelations. In this study, I take a different approach to bringing emic and etic perspectives together by placing a phenomenologically interpreted emic account of absorption (the meditative shift in consciousness) into dialogue with current scientific understandings of three central mental processes of meditation. Specifically, I analyze ways of conceptualizing attention, memory, and emotion, and their underlying mechanisms as posited in yoga and science, focusing on the problem of how each system interprets the reality of absorption. This comparison suggests a basic similarity between the two systems: theorizing cognition and meditative absorption in terms of embodiment. This finding emphasizes the dual nature of embodiment as both experiential and physical. Finally, I consider this dialogue from an embodied mind perspective, an emerging way of thinking about and theorizing the mind-body in cognitive science, because this perspective challenges longstanding theoretical problems in western understandings of how the mind works. This analysis suggests that theorizing meditation in these dual terms of embodiment potentially solves the reductive challenges of dualistic and materialist philosophy that have plagued both religious and naturalistic attempts to explain absorption. This interdisciplinary dialogue provides a framework with which to think more critically about translational and cross-disciplinary efforts that have previously confused the goals of yoga and science and their respective foci on practice and mechanisms. I conclude that bridging ideas in this dialogical way reveals a complementary perspective between phenomenological and biological ways of understanding the mind that both hinge on embodied cognition.
Genetically identified cholecystokinin neurons of the inferior colliculus provide direct excitation and inhibition to the medial geniculate body of the gerbil
(2018-08-15) Kreeger, Lauren Josephine; Golding, Nace L.; Chandrasekaran, Bharath; Johnston, Daniel; Priebe, Nicholas; Zemelman, Boris
Neurons in the central nucleus of the inferior colliculus (ICC) exhibit diverse morphologies, electrophysiological properties, and projection targets. Despite thorough characterization of these features, individual parameters cannot define functional classes. Neurochemical markers could be the answer to connecting form and function. By combining anatomy, physiology, and neurochemical markers, the experiments presented in this dissertation genetically identify cholecystokinin (CCK) neurons in the ICC of the Mongolian gerbil. CCK neurons comprise two classes, one excitatory and one inhibitory, that can be distinguished by both endogenous neurochemical markers and electrophysiological properties. Interdependent adeno-associated viruses were used to express fluorophores and opsins in CCK neurons in the ICC. The specificity of viral expression was confirmed using multiplexed in situ hybridization. To characterize the relationship between endogenous neurochemical markers and electrophysiological properties, we targeted genetically identified CCK neurons in the ICC for in vitro whole-cell current clamp recordings. Both excitatory and inhibitory CCK neurons have an adapting firing pattern. The two groups have distinct action potential signatures, which can be an electrophysiological marker to distinguish the groups. To find synaptic connections between CCK neurons and other neurons in the intrinsic ICC circuit, recordings were made from ICC neurons while CCK inputs were activated with channelrhodopsin. Excitatory and inhibitory post-synaptic potentials from CCK neurons are small and widespread, making connections with more than half of ICC neurons. CCK neurons in the ICC exclusively target the ventral division of the medial geniculate body (MGB), suggesting a functional role in the ascending lemniscal auditory pathway. Axons are highly branched with both fine axons with small boutons and en passant swellings, and medium to large axons with large terminal boutons. To characterize CCK inputs to the MGB, neurons in the vMGB were targeted for whole-cell recordings and CCK inputs were activated with channelrhodopsin. EPSPs and IPSPs are large, with EPSPs large enough to reliably induce action potentials in the post-synaptic vMGB neuron. EPSPs have both ionotropic and metabotropic components and exhibit short-term depression.
Identifying human 21st chromosome orthologs required for neuronal function in Caenorhabditis elegans
(2018-05) Nordquist, Sarah Katrina; Pierce-Shimomura, Jonathan T.; Aldrich, Richard W.; Atkinson, Nigel S.; Harris, R. A.; Marcotte, Edward M.
Down syndrome, caused by trisomy of the 21st chromosome, leads to lifelong cognitive impairment, characterized by alterations to neural cells and circuits, brain tissue, and behavior. Efforts to understand this disorder first require an understanding of the genes encoded on the 21st chromosome. The small roundworm, Caenorhabditis elegans, is an excellent model to uncover the in vivo function of human 21st chromosome orthologs. The first chapter of my dissertation provides background on Down syndrome—how it is thought to arise, the phenotypes it causes within the nervous system, which genes and pathways may underlie these phenotypes, and a brief survey of the established mouse models used to interrogate the disorder. I conclude by arguing that the more tractable model organism, C. elegans, can be used to complement research with rodents and that worm is a particularly fruitful system for initial gene characterization. In my next chapter, I discuss two systematic screens I performed on human 21st chromosome orthologs in worm: the first, a behavioral screen to identify genes broadly affecting nervous system function; the second, a pharmacological screen to identify genes involved in synaptic signaling. In these two screens, I identified a handful of candidate genes, several of which had not previously been linked to the nervous system in any animal. In Chapter 3, I discuss one of these novel candidate genes, mtq-2, that emerged from my screen. I provide a fuller characterization of it and show that it is required for normal nervous system function, normal excitatory neurotransmission, and that it functions, specifically, in cholinergic neurons to mediate its effects. I also discuss the potential genetic pathways in which mtq-2 may work to control synaptic vesicle release in excitatory motor neurons. Here, I present evidence that suggests mtq-2 may function upstream of or in conjunction with at least one Gα signaling protein, GαO. I conclude by sharing preliminary results on overexpression of mtq-2 and suggest future directions for inquiry.
Immunosuppressive effects of PEG-fusion in peripheral nerve allografts
(2021-03-08) Smith, Tyler Aaron; Bittner, George D.; Tucker, Haley O.; Sakiyama-Elbert, Shelly E.; Zakon, Harold; Poenie, Martin
Surgical repair of ablation-type peripheral nerve injuries by using peripheral nerve allografts (PNAs) has been hindered for decades due to slow and ineffective axon regeneration from proximal nerve ends as well as immunological rejection of PNAs. We have developed a polyethylene glycol (PEG)-fusion repair protocol for sciatic PNAs in rats that results in maintenance of myelinated axons that do not degenerate, neuromuscular junction innervation, and significantly improved behavioral recovery, as compared to current nerve repair methods. These phenotypes are maintained for weeks postoperatively without using tissue-matching, decellularization, or immunosuppressive drugs. That is, PEG-fused PNAs are functionally tolerated by the host immune system. This dissertation presents work performed to characterize and investigate mechanisms underlying immunological responses to PNAs treated with PEG-fusion with the aim of understanding how and why PEG-fused allografts are not rejected by the host immune system in rat sciatic nerve injury models. Chapter 1 provides a review of the clinical significance of peripheral nerve injury, including: Biological processes of axonal degeneration and regeneration, current methods of nerve repair, immunological rejection of PNAs, concepts underlying PEG-fusion repair and current experimental results of PEG-fusion in rat PNAs, as well as the hypotheses and aims explored. Chapter 2 characterizes innate and adaptive immune responses to PEG-fused PNAs using primarily immunohistochemistry, electron microscopy, and quantitative reverse transcription PCR (RT-qPCR). Our results suggest that PEG-fused PNAs achieve immunotolerance via attenuated innate and adaptive immune responses. Chapter 3 examines via RNA sequencing the coding transcriptome of PEG-fused PNAs to determine which biological processes, protein families, pathways, and protein-protein interaction networks differentiate PEG-fused PNAs from negative control PNAs not treated with PEG with the goal of identifying potential mechanisms underlying immunotolerance. This work provides a critical molecular foundation for future studies investigating PEG-fusion-mediated immunosuppression in PNAs. Chapter 4 investigates whether treatment of PNAs with PEG alone without axonal fusion induces similar immunosuppressive effects. Our results suggest that PEG treatment alone does not prevent Wallerian degeneration or attenuation of innate and adaptive immune responses. Chapter 5 provides a summary of the dissertation work and describes future directions for research.
Initial studies of two-photon line excitation array detection fluorescence microscopy
(2020-12-03) Wu, Frances Camille Masim; Ben-Yakar, Adela
Rapid, large-scale two-photon fluorescence microscope is essential in volumetric brain imaging. To study the behavior of highly interconnected neuronal circuits and monitor neuronal events i.e. action potentials at millisecond timescales, a two-photon fluorescence microscope with large field-of-view and fast imaging frame rate must be developed. Current advances in two-photon fluorescence imaging techniques have been circumscribed to either a large-scale imaging modality with slow imaging frame rate or a small-scale imaging technique with fast imaging speed. As a result, neuronal investigations are limited to studies in only a fraction of the brain with low spatial and temporal resolutions. To overcome this challenge, this thesis characterizes a custom-built rapid, large-scale two-photon fluorescence microscope, named two-photon line excitation array detection (2P-LEAD) fluorescence microscope. The 2P-LEAD fluorescence microscope combines rapid, line-scanning and fast imaging with a 16-channel photomultiplier tube array to be able to achieve high imaging frame rates. The 2P-LEAD fluorescence microscope studied in this thesis uses a galvanometric scanning mirror which is capable of imaging ~2,600 frames per second. An excitation line with a dimension of ~1 x 24 µm² (x x y 1/e² of intensity beam diameter) is scanned over a ~17 µm field-of-view using a ~1.3 kHz galvanometric mirror. The fluorescence is imaged onto a 16-channel photomultiplier tube in which each channel detects 1/16th of the fluorescence line. The detected fluorescence line is scanned across a ~16-mm active sensor channel length of the photomultiplier tube. A detailed systematic design of the optical parameters and the optimum selection of the optics used in the construction of the 2P LEAD fluorescence microscope are presented. Different microscope characterization techniques such as excitation beam imaging, fluorescence beam imaging, correction for fluorescence signal jittering, and signal-to-noise ratio measurements are also presented. The length of the excitation line at the sample focal plane (~7.7 µm, y, FWHM of intensity square beam diameter) coincides with the de-magnified fluorescence beam at the surface of the 16-channel photomultiplier tube. Fluorescence signal jittering which occurs at ~36.31 µs due to the mismatch between the excitation laser repetition rate and the acquisition frequency of the data acquisition card is corrected using frequency manipulation via the external clock. Furthermore, a signal-to-noise ratio of ~6 is achieved with the developed two-photon LEAD fluorescence microscope. Finally, a design of the future rapid, large-scale 2P-LEAD fluorescence microscope is presented. In the design, an excitation line with a dimension of ~1.5 x 240 µm² (x x y 1/e² of intensity beam diameter) is scanned over a ~100 µm field-of-view using a ~1.3 kHz galvanometric mirror. The fluorescence is detected by a 32-channel photomultiplier tube. To perform fast volumetric imaging of mouse brain in-vivo, a fast-lateral scanning unit i.e. resonant mirror (~24 kHz) or acousto-optic deflector (~MHz) and a fast aberration-free axial remote focusing unit i.e. voice-coil actuator can be incorporated in the custom-built 2P-LEAD fluorescence microscope. The proposed 2P-LEAD can be a promising imaging tool to perform rapid, large-scale mouse brain imaging in-vivo to investigate large volumes of neuronal networks and study neuronal events in millisecond or sub-millisecond timescales.
Neural speech tracking in quiet and noisy listening environments using naturalistic stimuli
(2020-05-10) Desai, Maansi; Hamilton, Liberty
In noisy situations, speech may be masked with conflicting acoustics, including background noise from the environment or other competing talkers. The process of listening to one stream of sounds while ignoring background noise is referred to as the “cocktail party problem,” but its physiological basis remains poorly understood. In this study, we used electroencephalography (EEG) to measure neural responses to a continuous, controlled clean speech stimulus versus speech in naturalistic noise in 17 participants with typical hearing. We employed linear encoding models to assess the degree of neural tracking to specific speech features. These models allow us to predict neural activity from EEG based on specific acoustic or linguistic features in the speech stimulus over time. The aims of this project were the following: 1) assess the fidelity of neural tracking of speech features using a highly uncontrolled and naturalistic stimulus containing speech-in-noise alongside a clean speech condition, 2) characterize neural responses to acoustic features such as the speech envelope and pitch, along with linguistic features such as phonological features in both speech-in-noise and speech alone stimuli, 3) utilize a cross-prediction analysis to predict the neural responses to a speech-in-noise condition from a clean speech condition, and vice versa. The first two analyses seek to understand which speech features drive brain responses measured from the scalp. The purpose of the third analysis is to understand whether the predictions from our encoding model are generalizable to different types of stimuli. Our results demonstrated that model performance was more robust for the phonological features compared to the acoustic envelope in clean speech conditions, but combining acoustic and phonological features aided in listeners tracking speech in a noisy condition. Our ability to predict neural activity in response to speech sounds was higher when those sounds occurred without background noise. Finally, we predicted responses to the clean speech stimuli based on responses to the noisy speech stimuli, and vice versa. These results have implications for identifying which speech features could be used to build a brain-machine interface or a cognitive hearing aid to identify and separate speech from noise.
Neuromarketing : an essential tool in the future of advertising and brand development
(2016-05) Hilderbrand, Miranda L.; Eastin, Matthew S.; Cicchirillo, Vincent J.
This research is designed to explore the future role of neuromarketing in advertising and brand development. To understand its necessity, the research will begin with an in-depth review on what is meant by advertising and branding. Once there is an understanding of these industries, the research will look at the field of neuromarketing – a history of the industry, an explanation of the common research methods that it employs, and an understanding of how neuromarketing can assist in advertising research and brand development. To gain knowledge on the potential future of neuromarketing, a qualitative study was done through a series of in-depth interviews with professionals who have practical uses for neuromarketing in their respective fields. This research is concluded with a summary the current state of neuromarketing, and a discussion on what needs to be done as the industry moves forward.
Pattern detection in natural images
(2016-12) Sebastian, Stephen P.; Geisler, Wilson S.; Bovik, Alan; Hayhoe, Mary; Cormack, Lawrence K; Seideman, Eyal
A fundamental visual task is to detect target objects within a background scene. Using relatively simple stimuli, vision science has identified several major factors that affect detection thresholds, such as the luminance of the background, the contrast of the background, the spatial similarity of the background to the target, and uncertainty due to random variations in the properties of the background and in the amplitude of the target. Here I use a new experimental approach together with a theoretical analysis based on signal detection theory, to discover how these factors affect detection in natural scenes. First, I sorted a large collection of natural image backgrounds into multidimensional bins, where each bin corresponds to a narrow range of luminance, contrast and similarity. Detection thresholds were measured by randomly sampling a natural image background from a bin on each trial. In low uncertainty conditions both the bin and the amplitude of the target were blocked and in high uncertainty conditions the bin and amplitude varied randomly on each trial. I found that thresholds increased approximately linearly along all three dimensions and that detection accuracy was unaffected by bin and amplitude uncertainty. The entire set of results was predicted from first principles by a normalized matched template detector, where the dynamic normalizing factor follows directly from the statistical properties of the natural backgrounds. This model assumed that the properties of the background underneath the target were constant across the image, but in natural images this is often not the case. Therefore, in a separate experiment, I measured detection thresholds on backgrounds where the contrast was modulated underneath the target. I found that varying the contrast underneath the target signal had a substantial effect on detectability, and that the pattern of results was predicted by an ideal observer that weighted its response based on an estimate of the local contrast (under the target). This suggests that the human visual system is able to use the varying properties of the background under the target in an near optimal way. Taken together, the results provide a new explanation for some classic laws of psychophysics and their underlying neural mechanisms.
Reinforcement learning strategies support generalization of learned hierarchical knowledge
(2021) McKee, Connor; Preston, Alison
In our everyday lives, we must learn and utilize context-specific information to inform our decision making. How do we learn what choices to make based on our memories? Prior rodent work has demonstrated that after learning, knowledge becomes organized hierarchically in a context-dependent manner. Here, we quantify the emergence of context-dependent hierarchical knowledge during learning and examine the flexible use of that knowledge to generalize across different scenarios. Participants learned about objects with context-dependent reward values in an X-shaped virtual environment consisting of an elongated, contextually-varying hallway with decision points on either end. First, participants learned the context-dependent object-reward pairings for one set of three objects. Next, they learned the context-dependent object-reward pairings for a new set of three objects. We hypothesized that prior knowledge of the hierarchical structure would generalize to the second set of objects as evidenced by a facilitation in learning rates. Participants gradually learned the context-dependent object-reward pairings during learning. When introduced to the new object set, learning rates did not significantly differ, indicating generalization of the hierarchical reward structure to the new object set. To further quantify how decision making unfolded, we applied three types of reinforcement learning (RL) models to our behavioral data: model-free, model-based (MB), and combination model-based model-free (MBMF). The MB model performed the best at using participants’ past selections to successfully predict future decisions and reward value expectations, indicating that current decisions were guided by prior selections. The MBMF model was best able to represent changes in participant learning across runs, possibly due to the model’s ability to assess different learning strategies. Overall, our results demonstrate that participants learned to flexibly decide which actions were the most adaptive, promoting correct decision-making in a given context. Furthermore, the structure of prior knowledge may support the generalization of learned experience.
Spatiotemporal dynamics of axonal reinnervation in the cerebellar cortex
(2013-08) Colonna, Jeremy Matthew; Nishiyama, Hiroshi; Harris, Kristen
Neuronal damage caused by brain injury or neurodegenerative disorders often leads to a loss of axonal innervation in distal target areas. Damaged axons typically do not regenerate in the central nervous system, but surviving axons can sprout new collaterals to re-innervate the denervated target area. At this point, it is unclear how long axons are capable of sprouting new collaterals after damage and the extent to which a surviving axon can expand its innervation area. To observe the spatiotemporal dynamics of collateral sprouting in the intact brain, we performed longitudinal time-lapse imaging of isolated cerebellar climbing fiber (CF) axons in vivo. Sub-populations of CFs were damaged by injecting neurotoxin 3-acetylpyridine into the inferior olivary nucleus (the origin of CFs) of transgenic mice that express enhanced green fluorescent protein (EGFP) in CF terminals. Time-lapse in vivo two-photon imaging of surviving, isolated EGFP-positive CFs revealed two distinct modes of axonal outgrowth: lateral outgrowth to expand CF innervation territory and outgrowth in the sagittal plane to innervate PCs within a CF’s existing territory. Lateral outgrowth appears to have a limited time window of 4-6 weeks after IO damage, but sagittal outgrowth continues after this period ends. Our data suggests that lateral expansion of CF innervation territory is likely guided by long-range attractive cues released by denervated PCs for a limited time after injury. On the other hand, sagittal expansion may be guided by constitutively expressed short range cues such as cell adhesion molecules expressed in the PC plasma membrane. Lateral outgrowth may allow CFs to innervate PCs in new functional zones, while sagittal outgrowth allows for the refinement of synaptic connections with PCs in a previously innervated functional zone.
Study of two-photon Line Excitation Array Detection microscopy
(2023-04-21) Murphy, Samuel Alexander; Ben-Yakar, Adela
The functional meaning associated with neuronal activity in the mammalian brain is an active area of research limited by the available microscope instrumentation. Exploring this domain of neuroscience necessitates high-speed 3D imaging operating over 1 kHz volumetric scan rates with sub-cellular resolution, as action potentials propagate on sub-millisecond time scales. Monitoring these signals requires in vivo experimentation, so additional care must be taken to avoid invasive methods that may damage sample tissue to live animal subjects. Multi-photon imaging provides an opportunity for non-invasive microscopy with optical sectioning while simultaneously deeply penetrating brain tissue. However, current multi-photon microscopy methods are limited to 10-100 Hz volumetric imaging rates. This thesis explores and expands upon a potential high-speed 2-photon imaging technology, 2-photon Line Excitation Array Detection (2p-LEAD) microscopy. 2p-LEAD combines line scanning with detection via a multi-channel photomultiplier tube (PMT) array, with the potential to operate at 125 kHz frame rates. In the experimental prototype outlined in this thesis, a 1035 nm excitation line of 2.4 µm x 259 µm (1/e2 beam intensity diameter) is scanned at the focal plane. The resulting fluorescence is collected by a 16-channel linear PMT array. With a fast-scanning galvanometric mirror, we scan the excitation line at 3,000 FPS, generating a 170 µm x 75 µm fluorescence FOV imaged to a 16 x 320 pixel frame. Temporal focusing was implemented to improve optical sectioning and signal-to-noise ratio (SNR), by reducing the out of focus fluorescent signal. This reduction was achieved by dispersing the pulse-width from 300 fs at the focus to multiple picoseconds. 0.5-2 µm fluorescent polystyrene beads were imaged to characterize the system resolution of 1-5.3 µm laterally. Thus this research lays the groundwork for 2p-LEAD imaging at 125 kHz, with an acousto-optic deflector replacing the galvo-mirror as the primary scanning element, for high-speed neuronal imaging.
Suppression of Defective Motor Patterns in Parkinsonian C. elegans
(2020-05) Chakka, Keerthana
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is caused partly by the loss of dopamine producing neurons. Dopamine is a conserved neuromodulator that aids in the transition between different motor patterns such as swimming, walking, or running. This can be observed across many species, including mice, flies, and nematodes. The cat-2 mutant strain of the nematode C. elegans has a deletion in the gene encoding tyrosine hydroxylase, an enzyme required to synthesize dopamine. Our lab recently demonstrated that the cat-2 mutant shares aspects of PD patient dysfunction through its inability to transition normally between the “swimming” and “crawling” patterns of motion. Currently, PD treatments focus on boosting residual dopamine signaling and are not available to maintain motor function once dopamine neurons completely degenerate. To search for ways to overcome motor dysfunction in the absence of dopamine, we performed a forward genetic screen to identify mutations that suppress poor swim-to-crawl motor transition in cat-2 mutant. We found several suppressor mutants that improve motor function. Further characterization can identify molecular pathways that can be altered to improve motor function in the absence of dopamine. This information could provide insight into repair of dopamine-deficient neural circuitry in higher level animals and possible approaches to help late stage PD patients.