Browsing by Subject "functional connectivity"
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Item Dynamic cortical networks in spontaneous and externally-driven locomotion(2022-11) West, SarahLocomotion requires extensive computations carried out across motor and sensory cortical regions to ensure safe and accurate navigation through the external environment. Motor cortical regions utilize sensory stimuli to adjust gait to avoid obstacles, while sensory cortical areas use internally-generated motor signals to predict corresponding sensory inputs. Despite the extensive cortical activation during locomotion, it is unclear how sensory and motor information are exchanged between areas or if they are organized via cortical-cortical mechanisms. To investigate these questions, wide-field Ca2+ imaging of the dorsal cerebral cortex was performed in mice during locomotion and the functional connectivity network formed by cortical areas was determined. The first hypothesis tested by this thesis was whether the cortical connectivity network forms a distinct structure during spontaneous locomotion than at rest, which would reveal an organizing mechanism of cortex-wide sensory-motor exchange. During locomotion, the correlations between most regions decrease, even as activity increases. However, connectivity between the secondary motor cortex (M2) and the rest of the cortex increased. These changes are independent of overall activity level and the step cycle, and causality analysis suggests information flows from M2 to other cortical regions. Combined with evidence from the literature, this suggests cortical activity during locomotion is organized by top-down signaling from M2 to each region. M2 and other upstream motor control areas are associated with the initiation of internally-driven movements, as opposed to externally-driven movements in response to external stimuli. Furthermore, little cortical input is required to generate simple gait patterns when an animal walks on a motorized treadmill. Therefore, we hypothesized that the organizing M2 connectivity structure would be diminished during motorized treadmill locomotion. To test this hypothesis, wide-field Ca2+ imaging was performed as mice walked spontaneously and on a motorized treadmill. M2 connectivity is indeed reduced during motorized treadmill locomotion compared to spontaneous, especially at locomotion onset and offset. Moreover, M2 connectivity is lower during deceleration of the treadmill than acceleration, and the spontaneous and motorized treadmill conditions induce different connectivity patterns in the periods immediately before and after walking. Together these results demonstrate that M2 organizing connectivity is engaged less in externally-driven movement, and that the differences between internally- and externally-driven locomotion control are evident at the level of the cortical functional network. This work has implications for locomotion pathologies, such as freezing-of-gait (FOG), that are linked to the internal generation of movement and the dysregulation of activity and connectivity of upstream motor cortical regions homologous to M2.Item An Investigation Into The Neural Nature Of Persecutory Ideation(2016-12) Wisner, KristaPersecutory ideation is a common and distressing symptom that exists on a continuum with persecutory delusions. Although associated with severe negative consequences the neural mechanisms underlying persecutory ideation remain unclear. Contributing factors in this research deficit include i) low rates of studies specifically examining persecutory ideation, favoring instead broader symptom measurement, and ii) a lack of paradigms that sufficiently engage or examine specific mechanisms associated with the symptom. In this dissertation, a wide range of literature is reviewed to identify brain regions consistently associated with delusions or positive symptoms in order to aid development of a model of persecutory ideation and stimulate research. Brain regions highlighted by the review represented a convergence of neurobiological models of delusions, and were the focus of two empirical studies. In the first study we employed a novel economic social decision-making task in two samples during neuroimaging. We demonstrated a dorsal anterior cingulate and anterior insula (dACC-AI) network, a left frontal-parietal (lF-P) network, and a ventral medial orbital prefrontal (vmPFC/OFC) network were associated with distinct forms of distrust. We then revealed only the connectivity between the vmPFC/OFC and lF-P networks predicted persecutory ideation, suggesting a role of weakened top-down control on subjective valuation. Moreover, we established this mechanism was associated with unique environmental influence in community monozygotic twins. In our second study we aimed to replicate the task-based finding in two resting-state samples to demonstrate generalizability of the mechanism; however, confirmatory analyses did not replicate. In summary, the posited vmPFC/OFC - lF-P interconnectivity mechanism of persecutory ideation appears to be uniquely evoked by the economic social decision-making task. While this provides a novel perspective on persecutory ideation, replications in larger samples are needed.