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Open Access Publications from the University of California

Scholarly Works (17 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2017)

Complex behavior demands interactions between an animal and its immediate environment. Spatial relationships are a critical component of nearly all such interactions. Accordingly, there exist distinct neural systems that construct and store representations of space. To effectively generate and utilize these spatial mappings, coordination must occur between cortical regions important for sensory processing and sub-cortical spatial systems, such as the hippocampus (HPC). The retrosplenial cortex (RSC) is a candidate structure to facilitate this coordination process, as it is anatomically positioned between the HPC formation and neocortex.

To investigate the role of RSC in spatial cognition, in vivo electrophysiological recordings were performed in rats during spatial navigation tasks. First, the spatial reference frames that influence RSC neuron firing were assessed in rats running routes placed at different environmental locations. RSC neurons encoded conjunctions between the animal’s position in the environment, position within a trajectory, and action state. Conjunctive sensitivity to multiple spatial variables suggested the region could interrelate representations encoded in distinct coordinate systems. In a second experiment, rats traversed a route with recurrent structure. Individual RSC neurons exhibited periodic activation patterns on the route that repeated across analogous route segments. Simultaneously, RSC ensembles defined a framework for the encoding of route segment positions relative to the whole. The nature of the firing activity provided a novel metric of distance from each route position to all others. Finally, neurophysiological signatures of interaction between RSC and HPC were identified. RSC neurons exhibited rhythmic spiking activity at temporal frequencies observed in HPC. These neurons, as well as those without rhythmic firing, could be temporally synchronized with synaptic inputs to the HPC. Additional interregional population interactions were observed during transient excitatory events in the HPC.

This work elucidates unique functions of RSC in transforming between spatial coordinate systems and parcellating complex space into sub-components. The experiments also identify the existence of novel symmetrical spatial activation patterns that construct a distributed distance code of the animal’s position from fixed points within a linear environment. Collectively, results from these studies indicate that RSC is a powerful hippocampal-cortical conduit capable of important computations relevant to spatial cognition.

    Cover page: Extraction and encoding of spatial relationships in the retrosplenial cortex
    • Thesis
    • Peer Reviewed
    UC San Francisco Electronic Theses and Dissertations (2016)

    Background and Objective:

    Oral health related quality of life (OHRQoL) is the aspect of one’s general well being, which is directly related to the mouth. Burdens on OHRQoL may deleteriously affect one’s ability to eat, speak, and socialize without discomfort, or embarrassment. However, different aspects of oral disease weigh against it in different ways. For instance, malocclusion affects different subdomains of OHRQoL than does caries. While the association between crooked teeth and social burdens has been reported, the relationship is unclear about how specific parameters of malocclusion like overbite or openbite may individually affect OHRQoL. Our objectives are to determine, in a sample group of adolescent and young adult subjects from Mexico and Peru: 1) how OHRQoL increases or decreases in relation to overbite; 2) to examine how overbite relates with subdomains of OHRQoL; and 3) to determine how severity on the spectrum of vertical dental relationships (severe deep bite through severe open bite) may alter the relationship between the oral health related quality of life. 4) To determine if there is an association between sleep disordered breathing, speech difficulties and vertical bite status.

    Materials and Methods:

    This was a cross-sectional, population-based, quantitative, epidemiological study. 2,042 subjects from 5 regions in Mexico and Peru aged 11-20 had their occlusion evaluated via the ICON index. Caries experience was quantified, via visual inspection, using the Decayed, Missing and Filled Surfaces (DMFS) index. Oral health related quality of life was measured with the COHIP-19 questionnaire. Vertical bite status, caries status, and malocclusion severity were analyzed in relation to quality of life, using ANOVA with bonferroni correction’s as needed. For dmfs a kruskal-wallis and mann-whitney U tests were used. Finally, a multivariate regression analysis was utilized to account for possible confounding factors as age, sex, and dmfs. Significance set at p<0.05.

    Results:

    51% of the study population was categorized as needing orthodontic treatment. 50% had severe caries experience (DMFS>5). Malocclusion severity was significantly associated with a decrease in OHRQoL (p<0.001). OHRQoL was significantly associated with caries in an inverse relationship for overall COHIP and all 6 subscales (p<0.001), except UC Emotional Well-Being (p=0.49). No significant association was found between vertical bite status and OHRQoL. DMFS for severe open bite subjects was significantly higher (dmfs=10.1 for open bite greater than 4mm) versus deep over bite subjects (dmfs=4.4 for fully covered overbites).

    Conclusions: In the regions studied and age group analyzed the following can be concluded.

    There is no association between overall OHRQoL, the subscales, and severity of vertical bite status in our population. There is a statistically significant decrease in Oral health related quality of life versus malocclusion severity and treatment need. There is a significant decrease in Oral health related quality of life versus caries experience except as it relates to ones attractiveness and confidence (Self esteem). There is a significant relationship between severe open bites and an increased caries experience.

      Cover page: Over bite status and its association with Oral Health Related Quality of Life in Adolescents and Young Adults
      • Thesis
      • Peer Reviewed
      UC Berkeley Electronic Theses and Dissertations (2013)

      Nanostructured block copolymer electrolytes containing an ion-conducting block and a modulus-strengthening block are of interest for applications in solid-state lithium metal batteries. These materials can self-assemble into well-defined microstructures, creating conducting channels that facilitate ion transport. The overall objective of this dissertation is to gain a better understanding of the behavior of salt-containing block copolymers, and evaluate their potential for use in solid-state lithium/sulfur batteries. Anionically synthesized polystyrene-b-poly(ethylene oxide) (SEO) copolymers doped with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt were used as a model system. This thesis investigates the model system on several levels: from fundamental thermodynamic studies to bulk characterization and finally device assembly and testing.

      First, the thermodynamics of neat and salt-containing block copolymers was studied. The addition of salt to these materials is necessary to make them conductive, however even small amounts of salt can have significant effects on their phase behavior, and consequently their ion-transport and mechanical properties. As a result, the effect of salt addition on block copolymer thermodynamics has been the subject of significant interest over the last decade. A comprehensive study of the thermodynamics of block copolymer/salt mixtures over a wide range of molecular weights, compositions, salt concentrations and temperatures was conducted. The Flory-Huggins interaction parameter was determined by fitting small angle X-ray scattering data of disordered systems to predictions based on the random phase approximation (RPA). Experiments on neat block copolymers revealed that the Flory-Huggins parameter is a strong function of chain length. Experiments on block copolymer/salt mixtures revealed a highly non-linear dependence of the Flory-Huggins parameter on salt concentration. These findings are a significant departure from previous results, and indicate the need for improved theories for describing thermodynamic interactions in neat and salt-containing block copolymers.

      Next, the effect of molecular weight on ion transport in both homopolymer and copolymer electrolytes were studied over a wide range of chain lengths. Homopolymer electrolytes show an inverse relationship between conductivity and chain length, with a plateau in the infinite molecular weight limit. This is due to the presence of two mechanisms of ion conduction in homopolymers; the first mechanism is a result of the segmental motion of the chains surrounding the salt ions, creating a liquid-like environment around the ion while the second mechanism of ion conduction is attributed to diffusion of the entire polymer chain with coordinated ions.

      Equilibrated block copolymer electrolytes exhibit a non-monotonic dependence on molecular weight, decreasing with increasing molecular weight in the small molecular weight limit before increasing when molecular weight exceeds about 10 kg mol-1

      The effect of morphology on ion transport was studied by conducting simultaneous impedance and X-ray scattering experiments as the block copolymer electrolyte transitioned from an ordered lamellar structure to a disordered phase. The ionic conductivity increased discontinuously through the transition from order to disorder. A simple framework for quantifying the magnitude of the discontinuity was presented.

      Finally, block copolymer electrolytes were examined specifically for use in high energy density solid state lithium/sulfur batteries. Such materials have been shown to form a stable interface with lithium metal anodes, maintain intimate contact upon cycling, and have sufficiently high shear moduli to retard dendrite formation. Having previously satisfied the concerns associated with the lithium metal anode, the compatibility of the sulfur cathode was explored. The sulfur cathode presents many unique challenges, including the generation of soluble lithium polysulfides (Li2Sx, 2 ≤ x ≤ 8) during discharge. The solubility of such species in block copolymers and their effect on morphology was examined. The lithium polysulfides were found to exhibit similar solubility in the block copolymers as in typical organic electrolytes, however induced unusual and unexpected phase behavior in the block copolymers.

      Inspired by successful efforts to physically confine the soluble lithium polysulfides via nanostructured carbon-sulfur composites in the cathode, our nanostructured block copolymer electrolytes were employed in full electrochemical cells with a lithium metal anode and sulfur cathode. Different cathode compositions, electrolyte additives, and cell architectures were tested. Surprisingly, the polysulfides diffused readily from the cathode through the block copolymer electrolyte, and the normally robust SEO|Li metal interface was detrimentally affected their presence during cycling. The polysulfides appeared to change the mechanical properties of the electrolyte such that intimate contact with the lithium metal was lost. Several promising strategies to overcome this problem were investigated and offer exciting avenues for improvement for future researchers.

        Cover page: Block Copolymer Electrolytes: Thermodynamics, Ion Transport, and Use in Solid-State Lithium/Sulfur Cells
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2019)

        Background

        Anxious temperament (AT) is an early-life heritable trait that predisposes individuals to develop anxiety and depressive disorders. Our previous work in preadolescent children suggests alterations in the uncinate fasciculus (UF), the white matter tract that connects prefrontal with limbic regions, in boys with anxiety disorders. Here, using a nonhuman primate model of AT, we tested whether this sexually dimorphic finding is evolutionarily conserved and examined the extent to which heritable and environmental influences contribute to UF microstructure.

        Methods

        Diffusion tensor images were collected in 581 young rhesus monkeys (1.89 ± 0.77 years old; 43.9% female). Using tract-based analyses, we assessed the relationship among AT, UF microstructure (as measured with fractional anisotropy), and sex. Heritability of tract microstructure was determined using oligogenic linkage analysis of this large multigenerational pedigree.

        Results

        We predicted and found a negative relation between AT and UF fractional anisotropy in male but not female monkeys (AT × sex; p = .032, 1-tailed). Additionally, heritability analyses revealed that variation in UF fractional anisotropy was largely due to nonheritable factors (h2 = 0.185, p = .077).

        Conclusions

        These results demonstrate a cross-species, male-specific relation between UF microstructure and anxiety and provide a potential substrate for anxiety-related prefrontal-limbic dysregulation. The heritability analyses point to the importance of environmental influences on UF microstructure, which could be important in mediating the nonheritable components of pathological anxiety. These findings have the potential to guide new treatment strategies for childhood anxiety disorders and further support the use of nonhuman primates as a translational model to discover mechanisms underlying the development of anxiety.
          Cover page: The Relationship Between the Uncinate Fasciculus and Anxious Temperament Is Evolutionarily Conserved and Sexually Dimorphic
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2014)
          Cortically projecting basal forebrain neurons play a critical role in learning and attention, and their degeneration accompanies age-related impairments in cognition. Despite the impressive anatomical and cell-type complexity of this system, currently available data suggest that basal forebrain neurons lack complexity in their response fields, with activity primarily reflecting only macro-level brain states such as sleep and wake, onset of relevant stimuli and/or reward obtainment. The current study examined the spiking activity of basal forebrain neuron populations across multiple phases of a selective attention task, addressing, in particular, the issue of complexity in ensemble firing patterns across time. Clustering techniques applied to the full population revealed a large number of distinct categories of task-phase-specific activity patterns. Unique population firing-rate vectors defined each task phase and most categories of task-phase-specific firing had counterparts with opposing firing patterns. An analogous set of task-phase-specific firing patterns was also observed in a population of posterior parietal cortex neurons. Thus, consistent with the known anatomical complexity, basal forebrain population dynamics are capable of differentially modulating their cortical targets according to the unique sets of environmental stimuli, motor requirements, and cognitive processes associated with different task phases.
            Cover page: Task-phase-specific dynamics of basal forebrain neuronal ensembles
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2024)
            BACKGROUND: Evidence suggests that early life adversity is associated with maladaptive behaviors and is commonly an antecedent of stress-related psychopathology. This is particularly relevant to rearing in primate species as infant primates depend on prolonged, nurturant rearing by caregivers for normal development. To further understand the consequences of early life rearing adversity, and the relation among alterations in behavior, physiology and brain function, we assessed young monkeys that had experienced maternal separation followed by peer rearing with behavioral, endocrine and multimodal neuroimaging measures. METHODS: 50 young rhesus monkeys were studied, half of which were rejected by their mothers and peer reared, and the other half were reared by their mothers. Assessments were performed at approximately 1.8 years of age and included: threat related behavioral and cortisol responses, cerebrospinal fluid (CSF) measurements of oxytocin and corticotropin releasing hormone (CRH), and multimodal neuroimaging measures (anatomical scans, resting functional connectivity, diffusion tensor imaging, and threat-related regional glucose metabolism). RESULTS: The results demonstrated alterations across behavioral, endocrine, and neuroimaging measures in young monkeys that were reared without their mothers. At a behavioral level in response to a potential threat, peer reared animals engaged in significantly less freezing behavior (p = 0.022) along with increased self-directed behaviors (p < 0.012). Levels of oxytocin in the CSF, but not plasma, were significantly reduced in the peer reared animals (p = 0.019). No differences in plasma cortisol or CSF CRH were observed. Diffusion tensor imaging revealed significantly decreased white matter density across the brain. Exploratory correlational and permutation analyses suggest that the impact of peer rearing on behavior, endocrine and brain structural alterations are mediated by separate parallel mechanisms. CONCLUSIONS: Taken together, these results demonstrate in NHPs the importance of maternal rearing on the development of brain, behavior and hormonal systems that are linked to social functioning and adaptive responses. The findings suggest that the effects of maternal deprivation are mediated via multiple independent pathways which may account for the heterogeneity in behavioral and biological alterations observed in individuals that have experienced this early life adversity.
              Cover page: Early life adversity in primates: Behavioral, endocrine, and neural effects.
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2022)
              Rats readily switch between foraging and more complex navigational behaviors such as pursuit of other rats or prey. These tasks require vastly different tracking of multiple behaviorally significant variables including self-motion state. To explore whether navigational context modulates self-motion tracking, we examined self-motion tuning in posterior parietal cortex neurons during foraging versus visual target pursuit. Animals performing the pursuit task demonstrate predictive processing of target trajectories by anticipating and intercepting them. Relative to foraging, pursuit yields multiplicative gain modulation of self-motion tuning and enhances self-motion state decoding. Self-motion sensitivity in parietal cortex neurons is, on average, history dependent regardless of behavioral context, but the temporal window of self-motion integration extends during target pursuit. Finally, many self-motion-sensitive neurons conjunctively track the visual target position relative to the animal. Thus, posterior parietal cortex functions to integrate the location of navigationally relevant target stimuli into an ongoing representation of past, present, and future locomotor trajectories.
                Cover page: Adaptive integration of self-motion and goals in posterior parietal cortex
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2018)
                Children with an extremely inhibited, anxious temperament (AT) are at increased risk for anxiety disorders and depression. Using a rhesus monkey model of early-life AT, we previously demonstrated that metabolism in the central extended amygdala (EAc), including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST), is associated with trait-like variation in AT. Here, we use fMRI to examine relationships between Ce-BST functional connectivity and AT in a large multigenerational family pedigree of rhesus monkeys (n = 170 females and 208 males). Results demonstrate that Ce-BST functional connectivity is heritable, accounts for a significant but modest portion of the variance in AT, and is coheritable with AT. Interestingly, Ce-BST functional connectivity and AT-related BST metabolism were not correlated and accounted for non-overlapping variance in AT. Exploratory analyses suggest that Ce-BST functional connectivity is associated with metabolism in the hypothalamus and periaqueductal gray. Together, these results suggest the importance of coordinated function within the EAc for determining individual differences in AT and metabolism in brain regions associated with its behavioral and neuroendocrine components.SIGNIFICANCE STATEMENT Anxiety disorders directly impact the lives of nearly one in five people, accounting for substantial worldwide suffering and disability. Here, we use a nonhuman primate model of anxious temperament (AT) to understand the neurobiology underlying the early-life risk to develop anxiety disorders. Leveraging the same kinds of neuroimaging measures routinely used in human studies, we demonstrate that coordinated activation between the central nucleus of the amygdala and the bed nucleus of the stria terminalis is correlated with, and coinherited with, early-life AT. Understanding how these central extended amygdala regions work together to produce extreme anxiety provides a neural target for early-life interventions with the promise of preventing lifelong disability in at-risk children.
                  Cover page: Functional Connectivity within the Primate Extended Amygdala Is Heritable and Associated with Early-Life Anxious Temperament
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2019)
                  OBJECTIVE:There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI. METHODS:Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI. RESULTS:Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common. CONCLUSIONS:Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.
                    Cover page: Use of magnetic resonance imaging in severe pediatric traumatic brain injury: assessment of current practice.
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2016)
                    Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.
                      Cover page: Sleep reverts changes in human gray and white matter caused by wake-dependent training
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