Browsing by Subject "Cerebellum"
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Item Adaptability of delay eyelid conditioning requires forebrain input to the cerebellum(2011-12) Houck, Brenda Diane; Mauk, Michael; Johnston, Daniel; Huk, Alexander C.; Jones, Theresa A.; Morikawa, HitoshiThe cerebellum is a region of the brain responsible for an organism’s ability to perform precise, coordinated movements. An abundance of research has characterized the anatomy of the cerebellum, and provides the foundation of current theories regarding the circuitry that supports motor learning. Delay eyelid conditioning is a form of motor learning. It is the learned association of a neutral stimulus and the reflexive response of an eyelid closure resulting in a well-timed eyelid closure in anticipation of the reflexive response. Two aspects of this learning are: different-conditioned stimulus savings and savings of timing. Different-CS savings is a rapid re-learning to a new, different neutral stimulus that occurs more quickly than learning to the original stimulus. Savings of timing is a phenomenon in which the timing of a response is preserved from a prior training experience. This dissertation presents evidence that forebrain input to the cerebellum is required for these aspects of delay eyelid conditioning. We trained animals with electrical stimulation as our neutral stimulus and thereby engaged a specific input pathway to the cerebellum, limiting forebrain inputs. In Chapter 2 we implement this technique and eliminate different-CS savings. These data suggest that forebrain input mediates this phenomenon. We then proceeded to investigate if the prefrontal cortex (PFC) is the forebrain region involved in supporting this aspect of delay eyelid conditioning. We administered electrolytic lesions to the PFC of animals and found their ability to express different-CS savings was impaired. Evidence from these two chapters suggests the PFC provides input to the cerebellum necessary for different-CS savings. Finally, in Chapter 4 we examine savings of timing. We again limit forebrain input to the cerebellum and implement electrical stimulation as our neutral training stimulus. With stimulation as the neutral stimulus, animals do not exhibit savings of timing. The data suggest that a forebrain region is necessary to sustain this phenomenon as well. This dissertation provides two lines of evidence strongly supporting forebrain involvement in these modifications of delay eyelid conditioning - savings and savings of timing. These results convey the importance of accommodating forebrain-cerebellum interactions when developing theories of cerebellar function.Item The assessment of autism risk and severity using prenatal ultrasound measures of the cerebellum(2012-05) Brinster, Meredith Irene; Allen, Greg, doctor of clinical psychology; Stark, KevinThe purpose of the current study is to contribute to the understanding of prenatal cerebellar pathology in autism. Reduction of Purkinje neurons is well reported in the cerebella of individual’s with autism. While there is evidence to suggest that this abnormality may be evident as early as prenatal development, no study to date has examined in the anataomical prenatal development of the cerebella in children later diagnosed with autism. The primary prediction being made is that a reduction of Purkinje neurons during prenatal development will present as reduced cerebellar size in the reports from mother’s prenatal ultrasound records. It is hypothesized that this reduction will be greater in children with an autism diagnosis compared to the records of children without an autism diagnosis. The secondary prediction will attempt to further support the link between aberrant cerebellar development and increased stereotyped behavior and repetitive interests. A retrospective analysis of prenatal ultrasound records and autism diagnostic information will test these hypotheses, predicting that records from children who have been diagnosed with an autism spectrum disorder will show reductions in transverse cerebellar diameter measurements when compared to TD peers, and that greater reductions will correlate with increased stereotypical and repetitive behaviors as measured by a standard diagnostic tool.Item Assessment of Cerebellar and Hippocampal Morphology and Biochemical Parameters in the Compound Heterozygous, Tottering/leaner Mouse(2010-07-14) Murawski, Emily M.Due to two different mutations in the gene that encodes the a1A subunit of voltage-activated CaV 2.1 calcium ion channels, the compound heterozygous tottering/leaner (tg/tgla) mouse exhibits numerous neurological deficits. Human disorders that arise from mutations in this voltage dependent calcium channel are familial hemiplegic migraine, episodic ataxia-2, and spinocerebellar ataxia 6. The tg/tgla mouse exhibits ataxia, movement disorders and memory impairment, suggesting that both the cerebellum and hippocampus are affected. To gain greater understanding of the many neurological abnormalities that are exhibited by the 90-120 day old tg/tgla mouse the following aspects were investigated: 1) the morphology of the cerebellum and hippocampus, 2) proliferation and death in cells of the hippocampal dentate gyrus and 3) changes in basic biochemical parameters in granule cells of the cerebellum and hippocampus. This study revealed no volume abnormalities within the hippocampus of the mutant mice, but a decrease in cell density with the pyramidal layer of CA3 and the hilus of the dentate gyrus. Cell size in the CA3 region was unaffected, but cell size in the hilus of the dentate gyrus did not exhibit the gender difference seen in the wild type mouse. The cerebellum showed a decrease in volume without any decrease in cerebellar cellular density. Cell proliferation and differentiation in the subgranular zone of the hippocampal dentate gyrus remained normal. This region also revealed a decrease in cell death in the tg/tgla mice. Basal intracellular calcium levels in granule cells show no difference within the hippocampus, but an increase in the tg/tgla male cerebellum compared to the wild type male cerebellum. There was no significant difference in granule cell mitochondrial membrane potential within the wild type and mutant animals in either the hippocampus or cerebellum. The rate of reactive oxygen species (ROS) production in granule cells revealed no variation within the hippocampus or cerebellum. The amount of ROS was decreased in cerebellar granule cells, but not granule cells of the hippocampus. Inducing ROS showed no alteration in production or amount of ROS produced in the hippocampus, but did show a ceiling in the amount of ROS produced, but not rate of production, in the cerebellum.Item Cerebellar tumor location as a predictor of neurocognitive functioning among survivors of pediatric brain tumors(2016-12) Mitchell Von Buttlar, Ashlee Beth; Allen, Greg, doctor of clinical psychology; Greenspahn, Emily SThe literature has clearly demonstrated that the cerebellum serves as a major processing center in the brain for many complex functional pathways ranging from attention and learning to emotions and affect. Research is now emphasizing the importance of connectivity between the cerebellum and other brain regions, and has begun highlighting the need to understand the impact of damage to distinct regions on functional pathways throughout the brain. One particular type of cerebellar damage, caused by posterior fossa tumors, has received substantial attention in the medical and neuropsychological literature in recent years. Tumors of the posterior fossa, which includes the cerebellum and brain stem structures, account for over 15% of brain tumors in children. Due to advances in treatment, survival rates have increased dramatically for individuals with posterior fossa tumors, leading to a greater need for long-term medical and psychosocial care. Treatments for these tumors, including chemotherapy and cranial radiation, are known to produce long-term deficits in a variety of neurocognitive domains. These deficits are referred to as “neurocognitive late effects,” and can be seen as impaired performance in the areas of attention, memory, executive functioning, visual-spatial processing, and processing speed. Neurocognitive late effects can be especially pronounced in patients with localized cranial radiation, as is common with malignant brain tumors. Research has clearly shown that different regions of the cerebellum uniquely contribute to various neurocognitive functions. Additionally, much research has assessed the neurocognitive implications of posterior fossa tumors in children. However, little work has examined the unique relationship between specific tumor locations within the cerebellum and later neurocognitive outcomes. The purpose of this document is to propose a study to determine whether the particular location of tumors in the cerebellum can predict neurocognitive functioning in the domains of attention and executive functioning in children with these tumors.Item Cerebello-striatal connectivity and implicit learning in autism spectrum disorders(2012-05) Morley, Richard Henry; Allen, Greg, doctor of clinical psychology; Schellart, Diane; Robinson, Daniel; Svinicki, Marillia; Stafford, MarkPrevious studies have indicated that persons with autism spectrum disorder have distinct cerebella, striatum, and an impaired ability to anticipate implicit learning sequences; also, previous research indicates anatomic connections among these regions. Investigating distinctions in connectivity and impairments in the ability to anticipate implicit sequences linked to ASD would help clarify some of the core deficits associated with the disorder. This dissertation sought to explore differences in functional connectivity among the cerebellum, thalamus, and striatum. This dissertation also sought to determine if an impaired ability to anticipate implicit sequences is associated with ASD. Twelve ASD participants and 11 control participants were scanned using an MRI while engaged in a modified serial reaction task. The findings indicate that the cerebellum and the striatum are functionally connected and the thalamus mediates this connection. The results indicate that ASD participants have stronger connections than the control, and ASD participants demonstrated some impairments in learning. However, there was not enough evidence to link ASD to an impaired ability to anticipate implicit sequences. This dissertation recommends that future studies consider the roles that these distinct connections play in symptoms of ASD.Item The cerebellum and divided attention in autism spectrum disorders(2014-08) Hsu, Julie Yong; Allen, Greg, doctor of clinical psychologyDivided attention, or the ability to respond to more than one task simultaneously, is an important skill for navigating complex social, communicative, academic, and professional settings. The purpose of the current study was to understand the association between the volume of the posterior cerebellum and divided attention in individuals with autism spectrum disorders (ASDs) and control participants. It was hypothesized that the ASD group would have worse divided attention abilities and smaller posterior cerebellar volumes compared to the control group. Furthermore, reduced posterior cerebellar volume was expected to be associated with weaker divided attention abilities. Participants were young adult males with high-functioning autism spectrum disorders (n=15) and controls matched for age, handedness, and nonverbal IQ (n=19). Results showed partial support for worse divided attention performance in ASDs and for a positive association between posterior cerebellar volume and divided attention performance. There were no group differences in posterior cerebellar volume, and accounting for intracranial volume did not affect findings. Limitations of the current study and future directions are discussed.Item Comparison of neural activation in the cerebellum in autistic adolescents with health control adolescents(2016-12) Thiruvettar-Sathishkumar, Mithra; Cormack, Lawrence K.Neuropathologic, neurochemical, and MRI (magnetic resonance imaging) anatomic studies have shown that the cerebellum is the most consistent site of brain abnormality in autism. However, there are very few functional MRI studies done to understand the functioning of this brain region in autism. In this study, we wanted to determine how the cerebellum responds during response inhibition. We compared neural activity in the cerebellar regions in autistic adolescents and control adolescents. Bonnet et al. (2009) describe two paradigms (Go task and Go/No-Go task) to determine response inhibition. We used similar paradigms in our study. 10 autistic and 10 control subjects were used for our study. Data were analyzed using Neuroimaging tool FSL (Smith et al. 2004). General Linear Model was used to test the hypothesis to determine if both groups have any difference in inhibition. Results show that the autistic group has more activation during response inhibition than the control group. This could be because of the loss of Purkinje cells (Bailey et al. 1998, Kemper et al. 1998). The brain may be rewiring itself and it may use a greater expanse of cerebellar tissue to achieve the same end goal.Item Developing an Educational Resource for Increasing Long-Term Retention of Cerebellar Circuitry and Pathways Implementing the Principles of Enduring Understanding(2010-01-12T18:59:05Z) Werkmeister, Robert Joseph; Krumwiede, Kim H.This thesis focuses on implementing the educational model of enduring understanding as it applies to the visual arts and neuroscience. The thesis was designed around developing an interactive web-based flash program intended to aid in medical students‘ retention of cerebellar circuitry at specific instances in their medical education. It focused on the visual and textual organization laid out within the principles of enduring understanding. By using the first two facets of enduring understanding, explanation and interpretation, the program was designed to teach medical students about the cerebellum‘s structure and function. Both facets provided a framework for the organization of the text and design of the illustrations, two and three-dimensional animations and questions sections. Testing was performed on medical students at varying levels in their medical education for gaps in knowledge and usefulness. These groups included first, second, and fourth year medical students, as well as residents. Further research will test the programs effect on students‘ efficiency and aptitude. Such testing will demand medical students‘ involvement over four years of schooling to determine the programs full efficacy. [Keywords: medical neuroscience; cerebellum; enduring understanding; medical illustration; interactive program]Item Effects of electrical stimulation and lesions of rostral fastigial nucleus on baroreceptor sensitivity and autonomic responses to transient changes in arterial blood pressure(Texas Tech University, 1986-08) Chen, Chu-huangNot availableItem Electrophysiological and pharmacological characterization of the serotonergic system on cerebellar purkinje cells(Texas Tech University, 1984-08) Lee, MunhyangIt has been shown that serotonergic fibers distribute widely in the cerebellum. The objectives of these experiments were to evaluate the effects of serotonin on cerebellar Purkinje cells and the influence of this substance upon the glutaminergic system within the cerebellum. This study consisted of four interrelated investigations. The first evaluated the responses of Purkinje cells to iontophoretically applied serotonin alone and in combination with various serotonin antagonists. It was observed that serotonin elicited one of three different effects on Purkinje cells: inhibition, excitation, or biphasic action consisting of inhibition followed by excitation. Excitatory effects of serotonin were antagonized or attenuated by iontophoretic application of the serotonin antagonist methysergide, whereas inhibitory effects were attenuated by the application of spiperone and ketanserin. These data suggest tentatively an involvement of different receptor sites for the inhibitory and excitatory effects of serotonin on Purkinje cells. The second set of experiments were conducted to investigate the actions of the cationic inhibitors of synaptic transmission, cobalt and manganese, and thereby determine whether presynaptic mechanisms were involved in the effects of serotonin. Excitations and inhibitions mediated by serotonin were not altered significantly in the presence of these ions. These data suggest that serotonin-mediated inhibitions and excitations may occur postsynaptically. Evaluation of the effect of serotonin on Purkinje cells after treatment with 5,7-dihydroxytryptamine (5,7-DHT) was the third part of this study. Serotonin applied microiontophoretically elicited the same effects on Purkinje cells in both treated and untreated animals: inhibition, excitation, or a biphasic effect. The spontaneous firing rates of the Purkinje cells were, however, shifted to lower frequencies after treatment with 5,7-DHT. In addition, the rate dependency of the activity of serotonin disappeared in animals treated with 5, 7-DHT. These results indicate that serotonin influences the spontaneous firing rate of Purkinje cells tonically in the normal state. The last part of this study was to evaluate the interaction of serotonin with the glutaminergic system that is known to exist in the cerebellum. Microiontophoretically applied serotonin inhibited the glutamate-induced excitation of Purkinje cells consistently. In conclusion, the present study suggests that the intrinsic serotonergic system exerts a tonic influence on the spontaneous firing rates of Purkinje cells. Secondly, microiontophoretically applied serotonin affects Purkinje cell firing directly and modulates glutamate-induced excitations of Purkinje cells.Item Fluid intelligence and the cerebellum in autism spectrum disorders(2013-08) Lane, Summer Elizabeth; Allen, Greg, doctor of clinical psychologyExecutive functioning abilities, including abstract reasoning, are often reported as weaknesses in autism spectrum disorders (ASDs). The current study examines reasoning through a different approach by utilizing the Cattell-Horn-Carroll (CHC) theory of intelligence, which is a widely accepted, research-based model that defines reasoning or fluid intelligence (Gf) and outlines those smaller skills of which it is composed. The Woodcock-Johnson, Third Edition (WJ III) is a test battery based on CHC theory, assessing the broad and narrow abilities of the model. Young men with high-functioning autism spectrum disorders (HFASDs) and neurotypical controls were given the WJ III tasks that assess the four narrow abilities of fluid intelligence - general sequential reasoning/deductive reasoning (RG), induction/inductive reasoning (I), speed of reasoning (RE), and quantitative reasoning/math reasoning (RQ). It was hypothesized that while deductive reasoning, inductive reasoning, and reasoning speed would be lower for HFASD, math reasoning would be comparable between groups. This expectation was based on previous autism research, which has found reasoning and processing speed deficits but preserved math skills. The present study also sought to examine cerebellar volume, through structural brain imaging, and its relationship to reasoning abilities. The HFASD group was expected to have reduced cerebellar volume when compared to controls. The ASD literature contains many examples of this pattern of brain structure, with the cerebellum being the most commonly cited region of abnormality. Additionally, the cerebellum has been implicated in studies of executive functioning, and a relationship between size and performance on nonverbal reasoning tasks has been reported. Therefore, a positive correlation was hypothesized between cerebellar volume and scores on WJ III reasoning tasks. Twenty-one young adult male HFASD subjects and 21 neurotypical controls were included in the current study. The data was analyzed through the use of MANOVA/MANCOVA, t-tests, and Pearson correlations. Results supported fluid intelligence weaknesses in the HFASD sample, with significantly lower performance in speed of reasoning. Deductive and inductive reasoning abilities were also lower, though these findings did not reach significance. The data did not support decreased cerebellar volume in HFASD, nor was a relationship between fluid reasoning and volume of the cerebellum found.Item The impact of childhood maltreatment on cerebellar volume(2014-12) Mann, Beatriz Elena; Allen, Greg, doctor of clinical psychologyThe purpose of the current study is to investigate the relationship between expusre to childhood maltreatment and the development of the cerebellar vermis and cerebrocerebellum. Reduced volumes in certain brian structures have been discovered in childhood maltreatment survivors, including the amygdala, hippocampus, and corpus callosum (Bremmer, et al., 1997; De Bellis, et al., 1999; Jackowski, et al., 2007; Teicher, et al., 2003; Teicher, et al., 2012). Furthermore, a number of studies have examined the impact of childhood abuse on cerebellar volume, suggesting that the cerebellum is susceptible to the effects of early stress (Anderson, et al., 2002; Bauer, et al., 2009; Beers & De Bellis, 2002; Carrion, et al., 2009; De Bellis & Kuchibhatla, 2006). However, few studies have examined the relation between type, frequency, and timing of maltreatment and cerebellar volume. Previous studies have addressed some of these questions, but had small sample sizes and were focused on different structures of the brain (rBRemmer, et al., 1997; De Bellis, et al., 1999). The current study proposes to examine cerebllar volume in relation to type, frequency, and timing of maltreatment with a considerably large sample size. It is hypothesized that there will be a significant relation between type, frequency, and timing of maltreatment and cerebellar volume. As the impact of maltreatment and development of the brain is still not fully understood, the current study seeks to contribute to the neuropsychological understanding of maltreatment and possibly shed light on potential treatment implications.Item Morphological variation in the cerebellum of the Passerine family Icteridae(Texas Tech University, 1972-12) Richards, FredNot availableItem Neurotoxic mechanisms of methylmercury: cellular and behavior changes(Texas A&M University, 2007-04-25) Bellum, SairamThe organic or methylated form of mercury (Hg), consisting of one methyl group bound to each atom of Hg, (methylmercury; MeHg), accounts for most of the Hg to which humans are exposed. MeHg, by virtue of its lipophilicity is highly neurotoxic to both the developing and mature central nervous system (CNS). Historically, MeHg has been implicated in high morbidity and mortality rates over the last 40 years in Japan, Iraq, Pakistan and Guatemala. The most common symptom exhibited in these exposure episodes was cerebellar ataxia. Recent in vitro studies using cultured granule cells showed that MeHg alters intracellular calcium ion ([Ca2+]i) homeostasis, potentiates reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential leading to apoptotic death of cerebellar granule neurons. To better understand the neurotoxic mechanisms of MeHg on cerebellum, changes with respect to biochemical processes in cerebellar granule cells and associated behavior changes were investigated. The aims of this dissertation were: (1) to assess mercury concentrations in mouse brain using different routes of administration and different tissue preparations, (2) to determine the behavior effects of in vivo MeHg exposure in young adult mice. (3) to understand specific biochemical processes leading to granule cell death/dysfunction due to in vivo MeHg toxicity in mice, and (4) to determine the toxic effects of in vivo MeHg exposure on mice aged between 16-20 months. The present results showed that repeated oral exposure to MeHg results in greater accumulation of Hg in brain tissue when compared to single oral or subcutaneous exposures at the same concentration of MeHg. Behavior analysis revealed that MeHg at the concentrations used in this study had profound effects on motor coordination and balance in young adult and aged mice. Investigation of biochemical processes in cerebellar granule cells of mice exposed to MeHg showed an increase in ROS generation, alteration of ([Ca2+]i (in young adult mice) and loss of MMP in young adult and aged mice. However, these changes did not lead to apoptotic cell death of granule cells at the concentrations of MeHg used and at the specific time point it was investigated in young adult mice.Item The relationship between posterior cerebellum volume and cross-modal divided attention in Autism Spectrum Disorders(2011-12) Hsu, Julie Yong; Allen, Greg, doctor of clinical psychology; Neff, KristinThe purpose of the current study is to understand the relationship between the volume of the posterior cerebellar hemispheres and cross-modality divided attention in ASD and control participants. Abnormalities in shifting, orienting, and selective attention are well reported in ASD, but few studies have examined divided attention. Furthermore, there is evidence of volumetric reduction of the posterior cerebellum in ASD. However, few studies have examined the relationship between the posterior cerebellum and behavioral performance. The current study addresses this gap in the literature through structural MRI and a neuropsychological attention task. It is hypothesized that the ASD group will have impaired divided attention abilities compared to the control group. Furthermore, within the ASD group, reduced posterior cerebellar volume is expected to be associated with impaired divided attention. The study will use multiple regression analyses. As ASD is a neurodevelopmental disability with considerable heterogeneity and unknown etiology, the current study seeks to contribute to the understanding of neural and behavioral markers of ASD.Item Resting state functional connectivity of the limbic cerebellum: vermis lobules IV, VII, and IX(2015-12) Kostic, Anne Cadence; Allen, Greg, doctor of clinical psychology; Stark, KevinThe cerebellum is classically known for its role in motor functioning; however, research has shown cerebellar involvement in other domains, including memory, attention, and emotional functioning. Animal studies, lesion studies, and imagining studies have contributed to our understanding of the wide array of cerebellar functions. Research specifically examining connections between the cerebellum and other systems of the brain has greatly expanded our understanding of the complexities of the cerebellum’s dynamic involvement with functional brain systems in addition to the motor system. Additionally, research has found the cerebellum to be involved in multiple disorders and is one of the most consistent sites of abnormality in autism. Connections between the cerebellum and the limbic system are thought to support cerebellar involvement in emotional functioning, affect, social cognition, and possibly in disorders indicative of impaired limbic-related functions, including autism. However, the functional connectivity of the limbic system and the cerebellum has not been comprehensively studied using functional connectivity magnetic resonance imaging (fcMRI) procedures. Therefore, the purpose of this present study is to determine the functional connectivity of specific cerebellar vermis with structures of the limbic system to contribute to the understanding of the organization of the limbic cerebellum. This study uses fcMRI and functional connectivity analysis to determine to functional coherence of three vermis ROIs with limbic structures. It is hypothesized that posterior vermis lobule ROIs will show significant functional coherence with limbic brain regions, suggesting posterior vermis involvement in the circuitry of the limbic cerebellum.Item Spatiotemporal dynamics of axonal reinnervation in the cerebellar cortex(2013-08) Colonna, Jeremy Matthew; Nishiyama, Hiroshi; Harris, KristenNeuronal 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.Item The effects of cerebellar stimulation or lesion on respiration(Texas Tech University, 1986-08) Williams, John LarryThese studies examined the influence of the cerebellum on respiration in anesthetized cats. Electrical stimulation of the rostral fastigial nucleus (rFN) in spontaneously breathing cats produced respiratory changes that correlated positively with the pressor responses. Thirty-seconds of stimulation at low frequencies (50 Hz or less) increased the respiratory rate (f) at all active sites. At approximately half the sites, stimulation at higher frequencies elicited apnea. At the remaining sites, f increased at all stimulation frequencies. Inspiratory duration (T-j.) decreased, and mean inspiratory flow increased. Tidal volume (V™) was unaltered. Similar changes occurred when the pressor response was blocked by phenoxybenzamine. In paralyzed animals, activity of the phrenic nerve served as an index of central respiratory activity. Results were similar, except that tidal neural activity (TNA; the neural correlate of V™) increased. In addition, minute neural activity (f x TNA) remained elevated for three minutes after stimulation.Item The impact of type, frequency, and age of exposure to childhood maltreatment on cerebellar volume(2016-12) Mann, Beatriz Elena; Allen, Greg, doctor of clinical psychology; Teicher, Martin Hersch; Anderson, Carl; Carlson, Cindy; Drum, DavidThe purpose of the current study was to investigate the relationship between exposure to childhood maltreatment and the development of the cerebellum. Reduced volumes in certain brain structures have been discovered in childhood maltreatment survivors, including the amygdala, hippocampus, and corpus callosum (Bremmer, et al., 1997; De Bellis, et al., 1999; Jackowski, et al., 2007; Teicher, et al., 2003; Teicher, et al., 2012). Furthermore, a number of studies have examined the impact of childhood abuse on cerebellar volume, suggesting that the cerebellum is susceptible to the effects of early stress (Anderson, et al., 2002; Bauer, et al., 2009; Beers & De Bellis, 2002; Carrion, et al., 2009; De Bellis & Kuchibhatla, 2006). However, few studies have examined the relation between type, frequency, and timing of maltreatment and cerebellar volume. The current study proposed to examine cerebellar volume in relation to type, frequency, and timing of maltreatment with a considerably large sample size. It was hypothesized that there would be a significant relation between type, frequency, and timing of maltreatment and cerebellar volume. Participants were young adults, ages 18-25 who fell along a continuum of maltreatment exposure (n=128). First, results suggest that exposure to maltreatment during childhood predicted smaller cerebellar volume. Second, unique clusters of cerebellar regions of interest (ROIs) were found to be significantly impacted by specific types of maltreatment experienced at certain ages, suggesting “developmental windows of vulnerability.” Third, results indicate that severity of maltreatment exposure was only predictive of reduced cerebellar volume in a very small region of the cerebellum. Finally, results suggest that type and timing of maltreatment predicted reduced cerebellar volume in the right hemisphere, the vermis, Crus II, and total cerebellar volume, according to the gender of participants. These results indicate that the cerebellum is negatively impacted by exposure to childhood maltreatment, that different types of maltreatment impact cerebellar volume differently, and that there may be sensitive periods of cerebellar development that make it more vulnerable to exposure to maltreatment. The importance of type and timing of maltreatment may also be different based on gender. Furthermore, results indicate that exposure to maltreatment during a cerebellar sensitive period may be more impactful compared to frequency, duration, or severity of maltreatment exposure.Item Timing in the cerebellum : a matter of network inhibition(2015-05) Li, Wenke; Mauk, Michael D.The motor functions of an animal require precisely timed and coordinated sequences of movements. The cerebellum is crucial for performing these functions with precision. To investigate cerebellar computations involved in precise motor movements, behavioral paradigms such as delay eyelid conditioning have been used. Delay eyelid conditioning trains an animal to close its eye in response to a previously neutral stimulus. The timing of the eyelid closure responses suggests that the cerebellum is capable of keeping track of the elapsed time since the onset of the stimulus. This dissertation proposes a network mechanism for cerebellar timing based on biologically informed simulations of the cerebellum. In chapter 2, a simulation with over a million cells is described. This simulation approaches the observed cerebellar connectivity in several well studied mammals. Graphics processing units (GPUs) provide the computational power necessary to perform this simulation at a practical speed. This chapter describes simulation algorithms that efficiently utilize GPUs. In chapter 3, the simulation is used to explore cerebellar timing mechanisms. The lateral inhibition among cerebellar Golgi cells is observed to be a potential mechanism for robust timing. Lateral Golgi inhibition enables the simulation to better replicate animal eyelid conditioning behavior for longer inter-stimulus intervals. In chapter 4, the emergent network mechanisms of lateral Golgi inhibition are analyzed by decomposing the network into its individual components. This component analysis demonstrates that nonreciprocal connectivity (where one Golgi cell inhibits another but does not receive inhibition in return) is useful for timing. Specifically, removing nonreciprocal connectivity greatly degrades the simulation's ability to keep track of time. This implies that the aforementioned component analyses are relevant to the emergent timing mechanisms of the network. Finally, in chapter 5, this dissertation discusses the relevance and limitations of the computational approach, biological predictions, and component analysis presented in previous chapters.