Browsing by Subject "Eye movements"

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    BEHAVIORAL AND NEURAL MECHANISMS UNDERLYING SPATIAL EXPLORATION AND DECISION
    (2014-06) Sakellaridi, Sofia
    The ability to explore novel environments and make decisions is a fundamental component of human and animal behavior. Even though significant progress has been made in recent years in understanding the mechanisms of exploration and decision-making, little is known on how the brain extracts, encodes and processes information from the environment to make decisions. The primary goal of this thesis is to understand the behavioral and neural mechanisms underlying the processing of spatial information, acquired during exploration of realistic environments to make spatial decisions. We designed a novel task, in which subjects had to explore maps from various U.S. cities to decide where to build a City Hall, while neuromagnetic fluxes were recorded from their heads using a whole-head MEG device. We found that ongoing neuronal activity in a network of cortical regions was associated with particular spatial parameters of the city maps. This network involved predominantly the right frontal and prefrontal areas of the brain, suggesting that these areas have an important role in processing spatial information for making decisions. Additionally, we found other brain areas that were also involved in the processing of spatial information, such as right temporal areas and the cerebellum. These results indicate that processing spatial information for making a decision is a complex process that requires the involvement of more than one regions. Finally, we found that the associations between changes in the ongoing neural activity and spatial parameters were modulated by the street network type. This suggests that, depending on the type of street network, people may use different spatial information to explore the map and make a spatial decision.We also studied how people make spatial decisions in realistic environments when they were forced to select between a limited set of choices. In this experiment, individuals had to explore maps from various U.S. cities, but now to select between two locations to build a hypothetical Post Office. We recorded subjects' eye positions and analyzed the gaze behavior to characterize how people explored maps to select between these options. We found that subjects were continuously exploring the areas around the two options and the center of the map, by looking back and forth between them before making a decision. Unlike economic choices, in which people follow similar strategies by looking repeatedly at the available options, in our experiment individuals were also exploring the area around the center of the map. These findings suggest that the subjects might have mentally placed themselves at the center of the map and evaluated the alternative options with respect to their current location. We also found other similarities with economic choice paradigms, such as people spent more time exploring the area around the option ultimately chosen. Finally, subjects showed a strong bias to select the option they initially explored.
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    Neurotrophic factor delivery to extraocular muscle: uncovering mechanisms of strabismus
    (2015-04) Willoughby, Christy Laura
    Strabismus is an ocular motor disorder characterized by eye misalignment, where clinically the extraocular muscle (EOM) pairs are presumed to be "overacting", and "underacting". There is currently a need for effective treatments that could act to strengthen an underacting muscle to aid in establishing eye alignment. Neurotrophic factors, such as insulin like growth factor-1 (IGF-1) and brain derived neurotropic factor (BDNF) have emerged as potential treatment options that could strengthen extraocular muscle. Neurotrophic factors have the ability to alter properties of EOM myofibers, neuromuscular junctions, and the motor neurons themselves through retrograde transport from the target muscle. A multi-action pharmacological agent that could be applied directly to the readily accessible EOM could present a clinically simple treatment for strabismus. In chapter 2, I build on previous work, which demonstrated that IGF-1 makes myofibers stronger. Rabbit EOM was pre-injected hepatocyte growth factor prior to IGF-1 treatment. With combined treatment, increased muscle force was obtained with lower doses of IGF-1. This work supports the potential therapeutic use of IGF-1 to correct strabismus by increasing muscle force. Despite the strong evidence that IGF-1 treatment strengthens EOM, the efficacy of IGF-1 to alter eye alignment in a binocular animal model is currently unknown. In chapters 3 and 4, I test the hypothesis that persistent bilateral (Chapter 3) or unilateral (Chapter 4) IGF-1 treatment to the medial rectus of a nonhuman primate can alter eye positioning. For these studies, we treated visually normal infant nonhuman primates during the postnatal development of the ocular motor system, which allowed us not only to assess if persistent IGF-1 treatment could disrupt the eye alignment, but also to investigate if aberrant neurotrophic factor signaling during development of the ocular motor system in the EOM is a possible cause of strabismus. In chapter 3, bilateral treatment did not result in strabismus. However, myofiber size increased in both the treated EOM and the untreated antagonist muscles. I hypothesize that over the three months of sustained treatment, the ocular motor system adapted to maintain eye alignment. In chapter 4, unilateral IGF-1 did create strabismus. This novel finding strongly suggests that altered molecular signaling by the EOM could be cause of strabismus. Finally, in Chapter 5, I extend my studies of neurotrophic factor treatment to infant nonhuman primates to test if another promising neurotropic factor, BDNF, could alter eye alignment during development of the ocular motor system. At the end of the three-month treatment period, no strabismus developed. However, there were marked changes to a subpopulation of myofibers that contain slow myosin heavy chain isoform. These results have interesting implications for the role of BDNF in selectively influencing tonic properties of the EOM. This work strongly demonstrates that sustained release of neurotrophic factors can significantly alter extraocular muscle properties, and disrupt eye alignment. Future studies will further investigate both the role of neurotrophic factors in determining normal EOM properties, and test if sustained release with IGF-1 can treat an animal model with strabismus.