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Open Access Publications from the University of California

Scholarly Works (59 results)

  • Article
  • Peer Reviewed
UC San Diego Previously Published Works (2018)
Eating disorders (ED), including Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED), are medically dangerous psychiatric disorders of unknown etiology. Accumulating evidence supports a biopsychosocial model that includes genetic heritability, neurobiological vulnerability, and psychosocial factors, such as stress, in the development and maintenance of ED. Notably, stress hormones influence appetite and eating, and dysfunction of the physiological stress response has been implicated in ED pathophysiology. Stress signals also appear associated with food reward neurocircuitry response in ED, providing a possible mechanism for the role of stress in appetite dysregulation. This paper provides a review of some of the interacting psychological, behavioral, physiological, and neurobiological mechanisms involved in the stress response among individuals with ED, and discusses novel neuroimaging techniques to address potential physiological confounds of studying neural correlates of stress in ED, such as calibrated fMRI.
    Cover page: The potential of calibrated fMRI in the understanding of stress in eating disorders.
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2019)

    Subjective cognitive decline (SCD) and possession of the ε4 allele of the apolipoprotein E (APOE) gene are both associated with increased risk for age-related cognitive decline and Alzheimer’s disease (AD). While mechanisms contributing to the increased risk associated with these factors are not well understood, evidence suggests that altered cerebral blood flow (CBF) may play a critical role. There is also evidence that altered CBF and brain structure among APOE ε4 carriers may interact to negatively impact cognition. The current studies utilized arterial spin labeling (ASL) magnetic resonance imaging (MRI) and high-resolution structural scans among cognitively normal older adults to determine the extent to which: 1) SCD modifies the effect of CBF on concurrent memory (Study 1), 2) APOE modifies effects of medial temporal lobe (MTL) CBF and brain structure (cortical thickness [CT], volume [Vo]) on concurrent memory (Study 2), and on 3) memory change (Study 3). Study 1 results showed that those with SCD exhibited positive associations between memory and CBF within the posterior cingulate cortex, middle temporal gyrus, and inferior frontal gyrus, whereas those without SCD displayed negative associations within the posterior cingulate cortex, middle temporal gyrus, hippocampus, fusiform gyrus, and inferior frontal gyrus. Findings suggest that while higher CBF is supportive of memory function in those without SCD, it may no longer support memory in those reporting SCD, likely reflecting neurovascular dysregulation. Results from Studies 2 and 3 demonstrated that, for APOE ε4 carriers, the combination of higher CBF and lower CT in the entorhinal cortex was associated with worse concurrent memory, but lower CBF and lower CT in this same region was associated with greater memory decline. Findings suggest that APOE ε4 carriers experience neurovascular dysregulation and concomitant morphological alterations in the MTL that interact to negatively affect cognition even in the absence of overt clinical symptoms. Results support the presence of distinct multimodal neural signatures in the entorhinal cortex that may signal relative risk for cognitive decline among ε4 carriers, likely reflecting different stages of neurovascular compensation. More broadly, results add to accumulating evidence supporting the early role of vascular dysregulation in AD risk.

      Cover page: Markers of Cognitive Decline: An Integration of Functional and Structural Neuroimaging, APOE Genotyping, and Neuropsychological Testing
      • Thesis
      • Peer Reviewed
      UC San Diego Electronic Theses and Dissertations (2021)

      Children with obesity (OB), relative to healthy-weight (HW), have reduced hippocampal volume and lower performance on hippocampal-dependent memory tasks. Little is known about whether differences occur across the weight range or in HW children. This three-paper dissertation aimed to 1) replicate and build upon prior volumetric findings in children with OB, relative to HW; 2) evaluate differences in hippocampal volume and tissue biology in youth across the weight range; and 3) examine differences in hippocampal structure and hippocampaldependent memory in HW children at high-risk (HR; two overweight/OB parents) or low-risk (LR; two HW parents) for obesity. Study 1 used magnetic resonance imaging (MRI) and measures of eating and eating habits in 25 8- to 12-year-old children (13 HW, 12 OB) to examine group differences in hippocampal volume and activation during a functional MRI taste task and explore associations between hippocampal volume and activation and eating/eating behaviors. Children with OB, versus HW, showed reduced left hippocampal volume and greater response to taste in three clusters within the left hippocampus. Moreover, activation within the hippocampus was positively associated with eating and eating behaviors. Study 2 used MRI in 102 adolescents across the weight range to examine the association between standardized BMI (BMIz), hippocampal volume, and tissue biology. BMIz was negatively associated with T2-weighted hippocampal signal intensity in bilateral hippocampi, suggesting differences in tissue biology. Study 3 used MRI, hippocampal-dependent memory tasks, and measures of eating and eating habits in 82 HW children (41 HR, 41 LR) to examine group differences in hippocampal volume and memory and explore whether volume and memory were associated with eating behaviors. HR children, relative to LR, had smaller left hippocampal volumes and lower performance on a hippocampal-dependent word memory task. Moderator models suggested that HR children, relative to LR, may already be showing patterns similar to children with OB. Collectively, these studies demonstrated differences in hippocampal structure and functioning in HW children at HR for OB, relative to LR (Study 1), and in children with OB, relative to HW (Study 2). Moreover, Study 3 findings suggest that, during adolescence, hippocampal differences related to increased weight reflect variations in tissue characteristics.

        Cover page: Hungry Hungry Hippocampus: Effects of overweight/obesity and risk for obesity on hippocampal structure and functioning in children and adolescents
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2016)

        Objective

        Eating disorders are complex psychiatric disorders, associated with alterations in neural and cognitive functioning. Research suggests inhibition and set-shifting deficits in anorexia nervosa (AN), but less is known about the persistence of these deficits after recovery, or their relationship to comorbid psychiatric symptoms.

        Method

        Women aged 19-45 remitted from AN (RAN, N = 47) and controls (CW, N = 24) completed the Delis-Kaplan Executive Function System Color-Word Interference Test. It was hypothesized that RAN, and those with higher anxiety or depression, would demonstrate worse Inhibition and Switching task performance than CW.

        Results

        Differences in performance between groups trended toward significance on Inhibition Ratio (p = 0.08) but were nonsignificant on Inhibition/Switching Ratio (p = 0.93). A model including State Anxiety and diagnosis revealed a significant independent effect of State Anxiety (p = 0.026), but not of diagnosis nor their interaction. Regressing State Anxiety on Color-Word Interference Test Inhibition among just the RAN group was significant [β = 0.37, t(46) = 2.63, p = 0.012] but among just CW was not (p = 0.54).

        Discussion

        Interference control for neutral stimuli is influenced by anxiety in women with a history of AN. Anxiety is linked with greater symptom severity among AN individuals, and state anxiety may account for larger deficits seen on tasks using disorder-specific stimuli. Future research is warranted to elucidate the nature of neuropsychological deficits in eating disorders. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.
          Cover page: Anxiety Impacts Cognitive Inhibition in Remitted Anorexia Nervosa
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2018)
          OBJECTIVES: Subjective cognitive decline (SCD), or self-reported cognitive decline despite normal neuropsychological test performance, is a risk factor for objective cognitive decline and Alzheimers disease (AD). While brain mechanisms contributing to SCD are not well defined, studies show associations with vascular risk factors and altered cerebral blood flow (CBF), raising the hypothesis that those with SCD might be experiencing vascular dysregulation, or a disruption in the normal relationship between CBF and cognition. We examined whether the association between CBF and verbal memory performance differs between those with SCD (SCD+) and those without SCD (SCD-). METHODS: Linear mixed-effects models were used to investigate whether the voxel-wise relationship between arterial spin labeling (ASL) MRI-measured CBF and verbal memory performance was modified by SCD among a group of 70 cognitively normal older adults (35 SCD+, 35 SCD-; mean age=72) matched on age, gender, and symptoms of depression. RESULTS: Results indicated that the SCD- group exhibited positive associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, and inferior frontal gyrus, whereas the SCD+ group displayed negative associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, hippocampus, fusiform gyrus, and inferior frontal gyrus. CONCLUSIONS: Findings suggest that, while higher CBF is supportive of memory function in those without SCD, higher CBF may no longer support memory function in those presenting with SCD, perhaps reflecting neurovascular dysregulation. (JINS, 2018, 24, 213-223).
            Cover page: Subjective Cognitive Decline Modifies the Relationship Between Cerebral Blood Flow and Memory Function in Cognitively Normal Older Adults.
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2024)
            Existing descriptions of the treatment of avoidant/restrictive food intake disorder (ARFID) at higher levels of care (HLOC) for eating disorders are limited, despite HLOC settings frequently serving patients with ARFID. The purpose of this commentary is to expand on the preliminary literature that describes pediatric ARFID treatment at HLOC by describing two specific components of our approach to treating pediatric ARFID that may not yet have traction in the current literature. Specifically, we highlight the utility of (1) treatment accommodations that appropriately account for patients neurodevelopmental needs (e.g., executive functioning, sensory processing) and (2) the adjunctive use of Dialectical Behavior Therapy (DBT) elements within family-based pediatric ARFID treatment. We also describe necessary future directions for research in these domains to clarify if incorporating these considerations and approaches into pediatric ARFID treatment at HLOC does indeed improve treatment outcomes.
              Cover page: Expanding considerations for treating avoidant/restrictive food intake disorder at a higher level of care.
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2020)
              When switching languages, bilinguals recruit a language control network that overlaps with brain regions known to support general cognitive control, but it is unclear whether these same regions are recruited in passive comprehension of language switches. Using fMRI with a blocked design, 24 Spanish-English bilinguals silently read 36 paragraphs in which the default language was Spanish or English, and that had either (1) no switches, (2) function word switches or (3) content word switches. Relative to no switches, function switches activated the right IFG, bilateral MFG, and left IPL/SMG. In contrast, switching on content words produced limited neural switching costs observed only in the left IFG. Switching into the dominant language was more costly in the right SMG than switching into the nondominant language, and neural switching costs were correlated with switching costs in the dominant language in cued picture-naming. Seemingly passive reading comprehension involves brain regions known to support cognitive control in active switching during production, possibly reflecting the operation of a modality-general switch mechanism.
                Cover page: Cognitive control regions are recruited in bilinguals silent reading of mixed-language paragraphs.
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2019)
                The pathophysiology of anorexia nervosa (AN) and bulimia nervosa (BN) are still poorly understood, but psychobiological models have proposed a key role for disturbances in the neuroendocrines that signal hunger and satiety and maintain energy homeostasis. Mounting evidence suggests that many neuroendocrines involved in the regulation of homeostasis and body weight also play integral roles in food reward valuation and learning via their interactions with the mesolimbic dopamine system. Neuroimaging data have associated altered brain reward responses in this system with the dietary restriction and binge eating and purging characteristic of AN and BN. Thus, neuroendocrine dysfunction may contribute to or perpetuate eating disorder symptoms via effects on reward circuitry. This narrative review focuses on reward-related neuroendocrines that are altered in eating disorder populations, including peptide YY, insulin, stress and gonadal hormones, and orexins. We provide an overview of the animal and human literature implicating these neuroendocrines in dopaminergic reward processes and discuss their potential relevance to eating disorder symptomatology and treatment.
                  Cover page: Neuroendocrinology of reward in anorexia nervosa and bulimia nervosa: Beyond leptin and ghrelin
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2019)
                  Introduction: Anorexia nervosa (AN) is associated with deficits in set-shifting and cognitive flexibility, yet less is known about the persistence of these deficits after recovery and how they might contribute to reported difficulties organizing and learning new information. To address this question, the current study applied a process-focused approach, that accounts for errors and strategies by which a score is achieved, to investigate the relationship between verbal memory and executive function in women remitted from AN. Method: Twenty-six women remitted from anorexia nervosa (RAN) and 25 control women (CW) aged 19-45 completed the California Verbal Learning Test, Second edition (CVLT-II) and the Wisconsin Card Sorting Test (WCST). Groups were compared on overall achievement scores, and on repetition, intrusion, and perseverative errors on both tests. Associations between learning and memory performance and WCST errors were also examined. Results: RAN and CW groups did not differ on overall CVLT-II learning and memory performance or errors on the WCST, though the RAN group trended towards greater WCST non-perseverative and total errors. On the CVLT-II, the RAN group made significantly more repetition errors than CW (p = 0.010), and within-trial perseveration (WTP) errors (p = 0.044). For the CW group, CVLT-II learning and memory performance were negatively associated with errors on the WCST, whereas among RAN, primarily delayed memory was negatively correlated with WCST errors. Notably, for RAN, greater WCST perseverative responses were correlated with greater CVLT-II repetition and WTP errors, showing the convergence of perseverative responding across tasks. Conclusions: Despite similar overall learning and memory performance, difficulties with executive control seem to persist even after symptom remission in patients with AN. Results indicate an inefficient learning process in the cognitive phenotype of AN and support the use of process approaches to refine neuropsychological assessment of AN by accounting for strategy use.
                    Cover page: A process approach to verbal memory assessment: Exploratory evidence of inefficient learning in women remitted from anorexia nervosa
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2022)

                    Objectives

                    Anorexia nervosa (AN) is associated with altered sensitivity to reward and punishment. Few studies have investigated whether this results in aberrant learning. The ability to learn from rewarding and aversive experiences is essential for flexibly adapting to changing environments, yet individuals with AN tend to demonstrate cognitive inflexibility, difficulty set-shifting and altered decision-making. Deficient reinforcement learning may contribute to repeated engagement in maladaptive behavior.

                    Methods

                    This study investigated learning in AN using a probabilistic associative learning task that separated learning of stimuli via reward from learning via punishment. Forty-two individuals with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 restricting-type AN were compared to 38 healthy controls (HCs). We applied computational models of reinforcement learning to assess group differences in learning, thought to be driven by violations in expectations, or prediction errors (PEs). Linear regression analyses examined whether learning parameters predicted BMI at discharge.

                    Results

                    AN had lower learning rates than HC following both positive and negative PE (p < .02), and were less likely to exploit what they had learned. Negative PE on punishment trials predicted lower discharge BMI (p < .001), suggesting individuals with more negative expectancies about avoiding punishment had the poorest outcome.

                    Conclusions

                    This is the first study to show lower rates of learning in AN following both positive and negative outcomes, with worse punishment learning predicting less weight gain. An inability to modify expectations about avoiding punishment might explain persistence of restricted eating despite negative consequences, and suggests that treatments that modify negative expectancy might be effective in reducing food avoidance in AN.
                      Cover page: Altered Reinforcement Learning from Reward and Punishment in Anorexia Nervosa: Evidence from Computational Modeling
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